porphobilinogen and Chronic Kidney Diseases studies

Research Excerpts

Excerpt	Relevance	Reference
"The acute hepatic porphyrias (AHP) are rare, inborn errors of heme-metabolism and include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase."	5.41	AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review. ( Balwani, M; Bonkovsky, HL; Lim, JK; Wang, B, 2023)
") Key secondary end points were levels of ALA and porphobilinogen and the annualized attack rate among patients with acute hepatic porphyria, along with hemin use and daily worst pain scores in patients with acute intermittent porphyria."	5.34	Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. ( Anderson, KE; Balwani, M; Bissell, DM; Bonkovsky, HL; Chen, J; Garg, P; Gouya, L; Harper, P; Horie, Y; Ivanova, A; Kauppinen, R; Keel, SB; Kim, JB; Ko, JJ; Langendonk, JG; Liu, S; Minder, E; Parker, C; Peiró, PA; Penz, C; Phillips, J; Rees, DC; Sardh, E; Silver, SM; Simon, AR; Stein, PE; Stölzel, U; Sweetser, MT; Vaishnaw, A; Vassiliou, D; Ventura, P; Wang, B; Wang, JD; Windyga, J, 2020)

Research

Studies (3)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Annualized Rate of Hemin Administration in Participants With AIP

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	1 (33.33)	24.3611
2020's	2 (66.67)	2.80

Authors	Studies
Wang, B	2
Bonkovsky, HL	2
Lim, JK	1
Balwani, M	2
Sardh, E	1
Ventura, P	1
Peiró, PA	1
Rees, DC	1
Stölzel, U	1
Bissell, DM	1
Windyga, J	1
Anderson, KE	1
Parker, C	1
Silver, SM	1
Keel, SB	1
Wang, JD	1
Stein, PE	1
Harper, P	1
Vassiliou, D	1
Phillips, J	1
Ivanova, A	1
Langendonk, JG	1
Kauppinen, R	1
Minder, E	1
Horie, Y	1
Penz, C	1
Chen, J	1
Liu, S	1
Ko, JJ	1
Sweetser, MT	1
Garg, P	1
Vaishnaw, A	1
Kim, JB	1
Simon, AR	1
Gouya, L	2
Pallet, N	1
Mami, I	1
Schmitt, C	1
Karim, Z	1
François, A	1
Rabant, M	1
Nochy, D	1
Deybach, JC	1
Xu-Dubois, Y	1
Thervet, E	1
Puy, H	1
Karras, A	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias[NCT03338816]	Phase 3	94 participants (Actual)	Interventional	2017-11-16	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Annualized rate of hemin doses was evaluated as annualized days of hemin use. (NCT03338816)
Timeframe: 6 months

Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)

Intervention	annualized rate of use (Mean)
Placebo	29.71
Givosiran 2.5 mg/kg	6.77

Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home. (NCT03338816)
Timeframe: 6 months

Annualized Rate of Porphyria Attacks in Participants With AHP

Intervention	annualized attack rate (Mean)
Placebo	12.52
Givosiran 2.5 mg/kg	3.22

Area Under the Curve (AUC) of the Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP

Intervention	annualized attack rate (Mean)
Placebo	12.26
Givosiran 2.5 mg/kg	3.35

Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores. (NCT03338816)
Timeframe: Baseline and 6 months

AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP

Intervention	score on a scale*week (Median)
Placebo	5.286
Givosiran 2.5 mg/kg	-11.514

Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores. (NCT03338816)
Timeframe: Baseline and 6 months

AUC of the Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP

Intervention	score on a scale (Least Squares Mean)
Placebo	-4.011
Givosiran 2.5 mg/kg	1.481

Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores. (NCT03338816)
Timeframe: Baseline and 6 months

Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP

Intervention	score on a scale*week (Least Squares Mean)
Placebo	-4.208
Givosiran 2.5 mg/kg	-11.148

Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP

Intervention	score on a scale (Least Squares Mean)
Placebo	-0.181
Givosiran 2.5 mg/kg	0.067

Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. (NCT03338816)
Timeframe: Baseline and 6 months

Average Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP

Intervention	score on a scale (Least Squares Mean)
Placebo	-0.182
Givosiran 2.5 mg/kg	-0.502

Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. (NCT03338816)
Timeframe: Baseline and 6 months

Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP

Intervention	score on a scale (Median)
Placebo	0.245
Givosiran 2.5 mg/kg	-0.506

The SF-12 is a survey designed for use in patients with multiple chronic conditions. This 12-item scale can be used to assess the physical and mental health of respondents. 10 of the 12 questions are answered on a 5 point likert scale and 2 are answered on a 3 point likert scale. The questions are then scored and weighted into 2 subscales, physical health and mental health. Respondents can have a score that ranges from 0-100 with 100 being the best score and indicating high physical or mental health. A 3 point change in SF-12 score reflects a meaningful difference. A higher score indicates improvement. (NCT03338816)
Timeframe: Baseline and 6 months

The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP

Intervention	score on a scale (Least Squares Mean)
Placebo	1.431
Givosiran 2.5 mg/kg	5.369

The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels. (NCT03338816)
Timeframe: 6 months

The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP

Intervention	mmol/mol Cr (Least Squares Mean)
Placebo	49.110
Givosiran 2.5 mg/kg	12.906

The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels. (NCT03338816)
Timeframe: 3 and 6 months

Intervention	mmol/mol creatinine (Cr) (Least Squares Mean)
	Month 3	Month 6
Givosiran 2.5 mg/kg	1.756	4.013
Placebo	19.965	23.150

porphobilinogen and Chronic Kidney Diseases