activins and Dysmyelopoietic Syndromes

activins has been researched along with Dysmyelopoietic Syndromes in 4 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 (4)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

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

Reviews

2 reviews available for activins and Dysmyelopoietic Syndromes

Trials

1 trial available for activins and Dysmyelopoietic Syndromes

Other Studies

1 other study available for activins and Dysmyelopoietic Syndromes