activins and Anemia, Cooley's

activins has been researched along with Anemia, Cooley's in 5 studies

Activins: Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.

Research

Studies (5)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

Apparent Clearance (CL/F) of Luspatercept

Apparent Clearance (CL/F) of Luspatercept (NCT03342404)
Timeframe: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months

Apparent Volume of Distribution of the Central Compartment (V1/F) of Luspatercept

Apparent Volume of Distribution of the Central Compartment (V1/F) of Luspatercept (NCT03342404)
Timeframe: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months

Area Under the Curve From Steady State (AUCss) of Luspatercept

Area Under the Curve From Steady State (AUCss) of Luspatercept (NCT03342404)
Timeframe: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months

Duration of the Mean Hemoglobin Increase From Baseline ≥1.0 g/dL

This outcome measure is the cumulative mean of the duration of hemoglobin response for the ≥ 1.0 g/dL during any 12-week rolling period. Any hemoglobin values within 21 days after a transfusion were excluded from the analysis. (NCT03342404)
Timeframe: From baseline up to approximately 56 months

Maximum Concentration (Cmax) of Luspatercept

Maximum Concentration (Cmax) of Luspatercept (NCT03342404)
Timeframe: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months

Maximum Concentration From Steady State (Cmax,ss) of Luspatercept

Maximum Concentration From Steady State (Cmax,ss) of Luspatercept (NCT03342404)
Timeframe: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months

Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 13 to Week 24)

Mean change from baseline in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 13 to Week 24 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 13 through week 24)

Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 37 to Week 48)

Mean change from baseline in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 37 to Week 48 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 37 through week 48)

Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)

"The FACIT-F is a multidimensional, self-report quality of life instrument which includes the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire (27 items over 4 different domains), and the Fatigue subscale (FS) component (13 items). FACIT-F version 4 has been used for this study. For the Fatigue subscale, each of the 13 items is scored from 0 (not at all) to 4 (very much). The scores from individual items are summed to generated the final FS score, which ranges from 0 (best outcome) to 52 (worst outcome). The questionnaire is completed every other dose, and the mean of FS scores from Week 13 to Week 24 is compared to the FS score at baseline (last score available before start of study treatment). Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13." (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 13 through week 24)

Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)

"The FACIT-F is a multidimensional, self-report quality of life instrument which includes the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire (27 items over 4 different domains), and the Fatigue subscale (FS) component (13 items). FACIT-F version 4 has been used for this study. For the Fatigue subscale, each of the 13 items is scored from 0 (not at all) to 4 (very much). The scores from individual items are summed to generated the final FS score, which ranges from 0 (best outcome) to 52 (worst outcome). The questionnaire is completed every other dose, and the mean of FS scores from Week 37 to Week 48 is compared to the FS score at baseline (last score available before start of study treatment). Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37." (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 37 through week 48)

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 13 to Week 24)

The NTDT-PRO V2.1 assess the severity of anemia-related symptoms associated with NTD β-thalassemia. It is a daily electronic diary with recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness (lack of energy) when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness (lack of strength) when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Shortness of Breath (SoB) domain score represents the average score of items 5 and 6 above. SoB domain score ranges from 0 (best outcome, no shortness of breath) to 10 (worst outcome, extreme shortness of breath). Weekly SoB Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12 week period (from Week 13 to Week 24) are compared to the SoB Domain Score at baseline. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 13 through week 24)

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 37 to Week 48)

NTDT-PRO V2.1 assess the severity of anemia-related symptoms. It is a daily recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Shortness of Breath (SoB) domain score represents the average score of items 5 and 6 above. SoB domain score ranges from 0 (best outcome, no shortness of breath) to 10 (worst outcome, extreme shortness of breath). Weekly SoB Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 37 to Week 48) are compared to the SoB Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 37 through week 48)

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 13 to Week 24)

The NTDT-PRO assesses the severity of anemia-related symptoms with a daily recall of symptoms composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Tiredness/Weakness (T/W) domain score is the average score of items 1 through 4 above. T/W domain score ranges from 0 (best outcome, no tiredness/weakness) to 10 (worst outcome, extreme tiredness/weakness). Weekly T/W Scores are the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 13 to Week 24) are compared to the T/W Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 13 through week 24)

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 37 to Week 48)

NTDT-PRO V2.1 assess the severity of anemia-related symptoms. It's a daily recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Tiredness/Weakness (T/W) domain score represents the average score of items 1 through 4 above. T/W domain score ranges from 0 (best outcome, no tiredness/weakness) to 10 (worst outcome, extreme tiredness/weakness). Weekly T/W Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 37 to Week 48) are compared to the T/W Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 37 through week 48)

Number of Participants With Anti-drug Antibody (ADA) Positive Test for Luspatercept

Presence of anti-drug (ACE-536/Luspatercept) antibodies was assessed every 24 weeks from serum samples. A participant is counted as 'positive' if there is any positive result captured during the study. (NCT03342404)
Timeframe: From first dose and up to 2 years following last dose, up to approximately 56 months

Percentage of Participants Achieving Erythroid Response (Week 13 to Week 24)

Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 13 to 24 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1. (NCT03342404)
Timeframe: From Week 13 to Week 24 of study treatment

Percentage of Participants Achieving Erythroid Response (Week 37 to Week 48)

Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 37 to 48 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1. (NCT03342404)
Timeframe: Assessed over a continuous 12 week period (from week 37 through week 48)

Percentage of Participants Who Are Transfusion-Free Over 24 Weeks

Transfusion free is defined as the absence of any transfusion during Week 1-24 of study treatment. Participants who discontinued treatment prior to Week 24 were not considered as transfusion free during Week 1-24. (NCT03342404)
Timeframe: From first dose to Week 24

Percentage of Participants Who Are Transfusion-Free Over 48 Weeks

Transfusion free is defined as the absence of any transfusion during Week 1-48 of study treatment. Participants who discontinued treatment prior to Week 48 were not considered as transfusion free during Week 1-48. (NCT03342404)
Timeframe: From first dose to Week 48

Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)

The FACIT-Fatigue, is a multidimensional, self-report quality of life instrument. It consists of 27 core items, the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, which assesses patient function in 4 domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by a 13-item measure designed to capture cancer-related fatigue, the Fatigue subscale (FS). The items are measured on a response scale with five options (0 = not at all to 4 = very much). Participants completed the questionnaire at screening and every other dose. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13. Score is calculated by multiplying the sum of item scores by the n of items in the scale, then divided by n of items answered. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 13 through week 24)

Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)

The FACIT-Fatigue, is a multidimensional, self-report quality of life instrument. It consists of 27 core items, the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, which assesses patient function in 4 domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by a 13-item measure designed to capture cancer-related fatigue, the Fatigue subscale (FS). The items are measured on a response scale with five options (0 = not at all to 4 = very much). Participants completed the questionnaire at screening and every other dose. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37. Score is calculated by multiplying the sum of item scores by the n of items in the scale, then divided by n of items answered. (NCT03342404)
Timeframe: Baseline and over a continuous 12 week period (from week 37 through week 48)

Percentage of Participants With an Increase From Baseline ≥1.5 g/dL in Mean Hemoglobin Values in the Absence of Transfusion

Percentage of participants who have an increase from baseline ≥1.5 g/dL in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 13 to Week 24 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1. (NCT03342404)
Timeframe: From Week 13 to Week 24 of study treatment

Time to Reach Maximum Concentration (Tmax) of Luspatercept

Time to Reach Maximum Concentration (Tmax) of Luspatercept (NCT03342404)
Timeframe: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months

Mean Change From Baseline in Liver Iron Concentration (LIC)

LIC was measured by Magnetic Resonance Imaging (MRI). Baseline is defined as the last value on or before the first dose of study drug is administered; Postbaseline is defined as the closest visit at Week 24 or Week 48. Participants with LIC value >43 are not included in the analysis. (NCT03342404)
Timeframe: Week 24 and Week 48 of study treatment

Mean Change From Baseline in Serum Ferritin

Baseline mean serum ferritin is calculated during the 24 weeks on or prior to dose 1 day 1. Post-baseline mean serum ferritin is calculated as mean of ferritin values during the last 24 weeks on or prior to the end date of the first 24 week or 48 week treatment (NCT03342404)
Timeframe: Week 24 and Week 48 of study treatment

Mean Change From Baseline in the 6-Minute Walk Test (6MWT) Distance

The 6MWT is typically used to objectively assess functional exercise capacity and response to medical interventions in patients with various moderate to severe diseases. Particiapnts are asked to walk as quickly as possible without running along a 30-meter corridor for six minutes, and the total distance covered during that time is measured. Baseline is defined as the last value on or before the first dose of study drug is administered. Postbaseline is defined as the closest visit at Week 24 or Week 48. (NCT03342404)
Timeframe: From baseline to Week 24 and from baseline to Week 48 of study treatment

Mean Change From Baseline in the Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of the Medical Outcomes Study 36-Item Short Form (SF-36)

The SF-36v2 is a 36-item generic PRO questionnaire used to assess patient-reported outcomes. The SF-36 yields scores for 8 domains of health: Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE), and Mental Health (MH) as well as physical component summary (PCS) and mental component summary (MCS) scores. Scores from each of the 8 domains of health are first normalized based on US general population means, then aggregated and transformed so that the scores from each of the 8 domains of health will contribute differently to the determination of PCS and MCS summary scores. PCS and MCS scores range from 0 to 100, with higher scores indicating a better quality of life. Baseline is defined as the last value taken on or before the first dose of study drug administered. (NCT03342404)
Timeframe: From baseline to Week 24 and from baseline to Week 48 of study treatment

Number of Participants Experiencing Adverse Events

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal. (NCT03342404)
Timeframe: From first dose to 63 days after last dose (up to approximately 56 months)

Percentage of Participants With a Decrease From Baseline ≥ RD (= 1) in the Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score

The responder definition (RD) threshold is the individual participant score change over a predetermined time period that will be interpreted as a treatment benefit. The RD for the NTDT-PRO T/W domain score was defined as ≥ 1-point decrease (ie, RD = -1) from baseline over the time from Week 13 to Week 24 or from Week 37 to Week 48. Participants with missing NTDT-PRO T/W scores at the indicated 12-week period are classified as non-responders in the analysis. (NCT03342404)
Timeframe: From Week 13 to Week 24 and from Week 37 to Week 48 of study treatment

Percentage of Participants With Improvement of Iron Overload

Iron overload was measured by Liver Iron Concentration (LIC) and Iron Chelation Therapy (ICT) daily dose. Improvement is defined as: - For participants with baseline LIC ≥3 mg/g: ≥20% reduction in LIC or ≥ 33% decrease in ICT daily dose - For participants with baseline LIC <3 mg/g: no increase in LIC >1 mg/g and not starting treatment with ICT, or no increase in ICT daily dose ≥ 33% (if on ICT at baseline) (NCT03342404)
Timeframe: Week 24 and Week 48 of study treatment

Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24

Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 24. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method. (NCT02631070)
Timeframe: From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks

Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48

Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 48. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method. (NCT02631070)
Timeframe: From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks

Overall Survival

Overall Survival was defined as the time from the date of study drug randomization to death due to any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for those who discontinued from the study or were lost to follow-up. (NCT02631070)
Timeframe: From randomization to study completion (up to approximately 57 months)

Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 24

RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 24 weeks of treatment. (NCT02631070)
Timeframe: From Week 1 through Week 24 of study treatment

Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 48

RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 48 weeks of treatment. (NCT02631070)
Timeframe: From Week 1 through Week 48 of study treatment

Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 Through Week 48

RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during Week 1 through Week 48. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 48 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to Week 48 were counted as non-responders. (NCT02631070)
Timeframe: From Week 1 through Week 48 of study treatment

Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 to Week 24

RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders. (NCT02631070)
Timeframe: From Week 1 through Week 24 of study treatment

Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)

Percentage of participants progressing to AML throughout the course of the study (NCT02631070)
Timeframe: From randomization to study completion (up to approximately 57 months)

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F)

Apparent total plasma clearance was calculated as Dose/Area Under the Curve to infinity (ꝏ). (NCT02631070)
Timeframe: Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F)

Apparent volume of distribution of luspatercept was calculated according to the equation Vz = (CL)/λ. (NCT02631070)
Timeframe: Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2)

Terminal phase half-life was calculated according to the following equation: t1/2 = 0.693/λz. (NCT02631070)
Timeframe: Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Area Under the Curve at Steady State for Starting Dose (AUC^ss)

Area under the curve steady state was defined as the area under the plasma concentration-time curve for a steady state. calculated by the linear trapezoidal rule. (NCT02631070)
Timeframe: Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the First Dose (Cmax)

Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration versus time. (NCT02631070)
Timeframe: Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) at Steady State

Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration at a steady state. (NCT02631070)
Timeframe: Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax)

Tmax was defined as the observed time to maximum plasma concentration of luspatercept. (NCT02631070)
Timeframe: Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.

Time to Acute Myeloid Leukemia (AML) Progression

Time to AML progression was defined as the time between randomization date and the first diagnosis of AML as per World Health Organization (WHO) classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with a diagnosis of AML were considered to have had an event, participants who did not progress to AML at the time of analysis were censored at the last assessment date which did not indicate progression to AML. (NCT02631070)
Timeframe: From randomization to study completion (up to approximately 57 months)

Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24

Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 24 (NCT02631070)
Timeframe: From first dose to Week 24 of study treatment

Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48

Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 48 (NCT02631070)
Timeframe: From first dose to Week 48 of study treatment

Change From Baseline in Mean Daily Dose of Iron Chelation Therapy (ICT)

Mean change from baseline in mean daily dose of ICT averaged over Week 9 to Week 24 or Week 33 to Week 48. For each participant, the mean change in daily dose of ICT was calculated as the difference of postbaseline mean daily dose and baseline mean daily dose. (NCT02631070)
Timeframe: Baseline and Week 9 through Week 24 and Week 33 through Week 48 of study treatment

Change From Baseline in Mean Serum Ferritin

Mean change from baseline in mean serum ferritin was calculated as the difference of postbaseline mean serum ferritin (averaged over the specified timepoints) and baseline mean serum ferritin. (NCT02631070)
Timeframe: Baseline and Week 9 through Week 24 and Week 33 through Week 48

Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period

Mean change in total number of Red Blood Cells (RBC) units transfused over a fixed 16-week period (Week 9-24 or Week 33-48) from the total number of RBC units transfused in the 16 weeks immediately on or prior to first dose of study treatment. (NCT02631070)
Timeframe: At Baseline (16 weeks prior to first dose of study treatment) and Weeks 9 to 24 or Weeks 33 to 48

Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Score

"The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. Version 3.0 of the questionnaire was used in the study.~It is composed of 30 items that address 15 domains, including one global health status, functional domains, and symptom domains. Domain scores are transformed to a 0 to 100 scale, where higher scores on the global quality of life score indicate better function. As such, a positive change from Baseline score indicates an improvement in quality of life." (NCT02631070)
Timeframe: Baseline and Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, every other cycle during extension phase (C1 D1, C3 D1, C5 D1, etc. up to C59 D1) and end of treatment. Each cycle is composed of 21 days.

Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Score

"The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. Version 3.0 of the questionnaire was used in the study.~It is composed of 30 items that address 15 domains, including one global health status, functional domains, and symptom domains. Domain scores are transformed to a 0 to 100 scale, where higher scores on the global quality of life score indicate better function. As such, a positive change from Baseline score indicates an improvement in quality of life." (NCT02631070)
Timeframe: Baseline and Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, every other cycle during extension phase (C1 D1, C3 D1, C5 D1, etc. up to C59 D1) and end of treatment. Each cycle is composed of 21 days.

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

"The outcome measure describes the number of participants who experienced different types of Treatment-emergent adverse events (TEAEs).~TEAEs were defined as Adverse Events (AEs) that started on or after the day of the first dose and on or before 42 days after the last dose of IP.~The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death." (NCT02631070)
Timeframe: From date of first dose up to 42 days after the last dose (up to approximately 83 weeks)

Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA)

"Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as treatment-emergent if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as preexisting if the baseline sample was ADA positive and the participant was not qualified for treatment-emergent." (NCT02631070)
Timeframe: From randomization to 1 year post first dose

Percentage of Participants Who Achieved a Hematologic Improvement in Neutrophil Response (HI-N) Over Any Consecutive 56-day Period

Percentage of participants who achieved a hematologic improvement in neutrophil response (HI-N) per IWG criteria sustained over any consecutive 56-day (8-week) period, during the treatment period (Week 1 to Week 24 and Week 1 to Week 48) HI-N was defined as at least a 100% increase and an absolute increase > 0.5 X 10^9/L. (NCT02631070)
Timeframe: Week 1 through Week 24 or Week 1 Through Week 48 of study treatment

Percentage of Participants Who Achieved a Hematologic Improvement in Platelet Response (HI-P) Over Any Consecutive 56-day Period

"Percentage of participants who achieved a hematologic improvement platelet response (HI-P) was defined as the percentage of participants meeting the HI-P criteria per the IWG sustained over any consecutive 56-day (8-week) period (Week 1 to Week 24 and Week 1 to Week 48) during the treatment period. HI - P reponse was defined as:~Absolute increase of ≥ 30 X 10^9/L in platelets for participants starting with > 20 X 10^9/L platelets~Increase in platelets from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%" (NCT02631070)
Timeframe: Week 1 through Week 24 or Week 1 Through Week 48 of study treatment

Percentage of Participants Who Achieved a Mean Hemoglobin (Hgb) Increase of at Least 1.0 g/dL Over Any Consecutive 56-Day Period in Absence of Red Blood Cells (RBC) Transfusions

A mean hgb increase of ≥ 1.0 g/dL was analyzed as the percentage of participants with a hgb increase ≥ 1.0 g/dL compared with baseline (after applying the 14/3 day rule) that was sustained over any consecutive 56-day (8-week) period in the absence of RBC transfusions during the treatment period. (Week 1 through Week 24 and Week 1 through Week 48). (NCT02631070)
Timeframe: Week 1 though Week 24 and Week 1 through 48

Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period

A modified HI-E response was defined as the percentage of participants meeting the modified HI-E per the International Working Group (IWG) sustained over 56-day consecutive period during the Treatment period. For participants with a baseline RBC transfusion burden of ≥ 4 units/8 weeks, a mHI-E was defined as a reduction in RBC transfusion of at least 4 units/8 weeks; for participants with baseline RBC transfusion burden of <4 units/8 weeks, mHI-E, was defined as a mean increase in hemoglobin of ≥ 1.5 g/dL for 8 weeks in the absence of RBC transfusions. (NCT02631070)
Timeframe: Week 1 through 24 or Week 1 Through Week 48

Longest Duration of Transfusion Independence

"Transfusion independence was defined as the absence of any transfusion during any consecutive rolling 8-week time interval within the treatment period, ie, Days 1 to 56, Days 2 to 57 and so on. Longest duration of transfusion independence was estimated based on Kaplan-Meier model." (NCT02604433)
Timeframe: From first dose through 3 weeks post last dose (up to approximately 218 weeks)

Mean Change From Baseline In Liver Iron Concentration (LIC) At Week 48

Baseline was defined as the last value on or before the first dose of study drug was administered; if multiple values were present for the same date, the average of these values was used. If a participant had 1 postbaseline assessment, it was used as the Week 48 value. If a participant had multiple postbaseline assessments, the last one was used as the Week 48 value. The value of LIC was collected by magnetic resonance imaging. Participants with a LIC value > 43 mg/g were not included in the analysis. (NCT02604433)
Timeframe: Baseline: Week -12 to Day -1; Treatment: Week 48

Mean Change From Baseline In Mean Serum Ferritin At Week 48

For each participant, the baseline mean serum ferritin level was calculated during the 12 weeks prior to first study drug administration. The postbaseline mean serum ferritin level was calculated during the last 12 weeks of the 48-week double-blind Treatment Period or last 12 weeks of study treatment, if discontinued early. The change was calculated as the difference of post baseline mean serum ferritin level and baseline mean serum ferritin level. (NCT02604433)
Timeframe: Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48

Mean Change From Baseline In Myocardial Iron At Week 48

Myocardial Iron levels were measured by Magnetic Resonance Imaging (MRI), using MRI parameter T2* (Unit: ms). T2* values correlates with heart failure (HF) risk (e.g. T2*<6ms: high HF risk). (NCT02604433)
Timeframe: Baseline: Day 1; Treatment: Week 48

Mean Change From Baseline in Transfusion Burden - Week 13 to Week 24

Baseline was defined as the total number of Red Blood Cells (RBC) units transfused during the 12-week interval on or prior to Dose 1 Day 1. This is compared to the total number of RBC units transfused during the 12-week interval from treatment weeks 13-24. (NCT02604433)
Timeframe: Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24

Number of Days Spent in Higher Care Hospital Units

Types of hospitals units considered to be 'higher care' are: - Intensive Care Unit - Coronary Care Unit (NCT02604433)
Timeframe: From informed consent signing (up to 12 weeks before start of treatment) to end of treatment (up to approximately 227 weeks)

Percentage Of Participants Who Achieve ≥ 50% Reduction From Baseline in Transfusion Burden - Week 13 to Week 24

Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 50% with a reduction of at least 2 units during Weeks 13 - 24 compared to the 12-week interval on or prior to Dose 1 Day 1. (NCT02604433)
Timeframe: Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24

Percentage Of Participants Who Achieve ≥ 50% Reduction From Baseline in Transfusion Burden - Week 37 to Week 48

Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 50% with a reduction of at least 2 units during Week 37 to Week 48 compared to the 12-week interval on or prior to Dose 1 Day 1. (NCT02604433)
Timeframe: Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48

Percentage Of Participants Who Achieved ≥ 33% Reduction From Baseline in Transfusion Burden - Week 37 to Week 48

Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 33% with a reduction of at least 2 units during Weeks 37 - 48 compared to the 12-week interval on or prior to Dose 1 Day 1. (NCT02604433)
Timeframe: Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 48

Percentage of Participants Who Achieved Erythroid Response - Week 13 to Week 24

Erythroid Response was defined as red blood cell (RBC) transfusion burden reduction from baseline ≥ 33% with a reduction of at least 2 units during Week 13 - 24 compared to the 12-week interval on or prior to Dose 1 Day 1. (NCT02604433)
Timeframe: Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24

Percentage Of Participants Who Were Transfusion Independent For ≥ 8 Weeks During Treatment

"Transfusion independence was defined as the absence of any transfusion during any consecutive rolling 8-week time interval within the treatment period, i.e, Days 1 to 56, Days 2 to 57 and so on." (NCT02604433)
Timeframe: From first dose through 3 weeks post last dose (up to approximately 218 weeks)

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F)

(NCT02604433)
Timeframe: Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F)

(NCT02604433)
Timeframe: Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Area Under the Concentration-Time Curve at Steady State for the Starting Dose (AUCss)

(NCT02604433)
Timeframe: Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2)

(NCT02604433)
Timeframe: Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration at Steady State for the Starting Dose (Cmax,ss)

(NCT02604433)
Timeframe: Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax)

(NCT02604433)
Timeframe: Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337

Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax)

(NCT02604433)
Timeframe: Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337

Duration of Reduction in Transfusion Burden

Responders were defined as subjects who achieved ≥ 33% reduction or ≥ 50% reduction in Red Blood Cells Transfusion (RBC-T) burden from baseline with a reduction of at least 2 RBC units during any rolling 12-week interval. The duration of reduction is calculated as Last Day of Response - First day of response +1 (NCT02604433)
Timeframe: From first dose to end of study treatment (up to approximately 215 weeks)

Mean Change From Baseline In Mean Daily Dose Of Iron Chelation Therapies (ICT) At Week 48

Three different types of Iron Chelation Therapy (ICT) were analyzed: 1. Deferasirox 2. Deferiprone 3. Deferoxamine Mesilate/Deferoxamine The baseline mean daily dose was calculated using the ICT dosage during the 12 weeks prior to first study drug administration and the postbaseline mean daily dose was calculated during the last 12 weeks of the 48-week double-blind Treatment Period or the last 12 weeks of the study treatment for early discontinued participants. (NCT02604433)
Timeframe: Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48

Mean Change From Baseline in the 36-item Short Form Health Survey (SF-36) Questionnaire At Weeks 24

The SF-36 (version 2) is a generic, self-administered instrument consisting of 8 multi-item scales that assess 8 health domains. The raw score for each health domain is transformed into a 0 (worst) to 100 (best) domain score. The 0-100 scale score for each health domain is further converted to normbased scores using a T-score transformation, with a mean of 50 and a standard deviation (SD) of 10. Higher norm-based T-scores indicate better heath/QoL. The domains/summaries reported are: 1. Physical Functioning (Range of possible T-scores is 19.26 - 57.54) 2. General Health (Range of possible T-scores is 18.95 - 66.50) 3. Physical Component summary (PCS) (Range of possible T-scores is 5.02 - 79.78). Positive change from baseline values indicate improvement. (NCT02604433)
Timeframe: Baseline: 4 weeks prior to Day 1; Treatment: Weeks 24

Mean Change From Baseline in the Transfusion-dependent Quality of Life (TranQol) Questionnaire At Week 24

The TranQol is a self-administered quality of life tool developed for beta-thalassemia patients. The adult self-report version used in this study, includes 36 questions assessed on a 5-point response, that are grouped into 5 domains (Physical Health, Emotional Health, Sexual Health, Family Functioning, School/Career Functioning). Scores are calculated according to specific scoring algorithms developed by the authors. Both individual domains score and the total score range from 0 (worst) to 100 (best). Total Score and Physical Health domain score are reported. Positive change from baseline values indicate improvement. (NCT02604433)
Timeframe: Baseline: 4 weeks prior to Day 1; Treatment: Week 24

Mean Change From Baseline In Total Hip And Lumbar Spine Bone Mineral Density (BMD) At Week 48

For BMD, the lumbar spine and total hip were measured at baseline and 48 weeks by dual energy x-ray absorptiometry (DXA). Baseline was defined as the last value on or before the first dose of study drug is administered; if multiple values are present for the same date, the average of these values was used. If during the 48 week double-blinded treatment period, a participant has only one assessment, it is counted as 'Week 48' visit; if a participant has multiple assessments, the last one is used as 'Week 48' visit. The analysis was done on the population that had at least 2 measurements. (NCT02604433)
Timeframe: Baseline: Day 1; Treatment: Week 48

Number of Participants Who Utilized Healthcare Resources During Study

Number of participants who had any of the following types of Healthcare Resource Utilization (HRU): - a doctor office visit (non-study scheduled) - an emergency department visit - a hospitalization (NCT02604433)
Timeframe: From informed consent signing (up to 12 weeks before start of treatment) to end of treatment (up to approximately 227 weeks)

Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA)

"Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as treatment-emergent if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as preexisting if the baseline sample was ADA positive and the participant was not qualified for treatment-emergent." (NCT02604433)
Timeframe: Timeframe: pre-dose, Day 1, Days 22, 64, 106, 148, 232, 316

Participants With Treatment-Emergent Adverse Events (TEAE)

An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A serious AE is any AE occurring at any dose that - Results in death - Is life-threatening - Requires or prolongs existing inpatient hospitalization - Results in persistent or significant disability/incapacity - Is a congenital anomaly/birth defect - Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention) - Grade 3 = Severe (limitation in activity; medical intervention required) - Grade 4 = Life-threatening - Grade 5 = Death (NCT02604433)
Timeframe: From first dose to 90 days following last dose (up to approximately 52 months)

Post-Baseline Transfusion Event Frequency

The number of transfusion events after start of study treatment were evaluated. For the definition of transfusion events, if multiple transfusions happen on the same date, they are counted as one event; if multiple transfusions happen on two consecutive dates, they are counted as one event; if multiple transfusions happen on three consecutive dates, they are counted as two events. Results are presented in 24-week intervals, up to 96 weeks after start of study treatment (NCT02604433)
Timeframe: From first dose through 3 weeks post last dose (up to approximately 218 weeks)

Time to Erythroid Response

Time to erythroid response was defined as the time from first dose of the study drug to first erythroid response. This is reported for participants with a ≥ 33% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) for any 12-week interval., as well as participants with a ≥ 50% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) for any 12-week interval. (NCT02604433)
Timeframe: From first dose to 48 weeks following first dose

Reviews

2 reviews available for activins and Anemia, Cooley's

Trials

2 trials available for activins and Anemia, Cooley's

Other Studies

1 other study available for activins and Anemia, Cooley's