Phase 3 N=94 Randomized Quadruple-blind Treatment

ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)

Acute Hepatic Porphyria · Acute Intermittent Porphyria · Porphyria, Acute Intermittent · Acute Porphyria · Hereditary Coproporphyria (HCP)

Bottom Line

View on ClinicalTrials.gov: NCT03338816 ↗

Enrolled (actual)

Serious AEs

31.2%

Results posted

Feb 2020

Primary outcome: Primary: Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) — 12.52; 3.22 annualized attack rate — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Givosiran (Drug); Placebo (Drug)
Age: Pediatric, Adult, Older Adult · 12+ yrs
Sex: All
Sponsor: Alnylam Pharmaceuticals
Primary completion: Jan 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)	12.52; 3.22	<0.0001 sig
SECONDARY The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP	19.965; 1.756; 23.150; 4.013	—
SECONDARY The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP	49.110; 12.906	—
SECONDARY Annualized Rate of Hemin Administration in Participants With AIP	29.71; 6.77	—
SECONDARY Annualized Rate of Porphyria Attacks in Participants With AHP	12.26; 3.35	—
SECONDARY 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	5.286; -11.514	—
SECONDARY 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	0.245; -0.506	—
SECONDARY 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	-4.208; -11.148	—
SECONDARY 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	-0.182; -0.502	—
SECONDARY AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP	-4.011; 1.481	—
SECONDARY Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP	-0.181; 0.067	—
SECONDARY Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP	1.431; 5.369	—

Summary

The purpose of this study is to evaluate the effect of subcutaneous givosiran (ALN-AS1), compared to placebo, on the rate of porphyria attacks in patients with Acute Hepatic Porphyrias (AHP).

Eligibility Criteria

Inclusion Criteria

≥ 12 years of age
Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, aminolevulinic acid (ALA) dehydratase deficient porphyria)
Elevated urinary or plasma porphobilinogen (PBG) or ALA values within the past year,
Have active disease, with at least 2 documented porphyria attacks within the last 6 months
Willing to discontinue or not initiate the use of prophylactic hemin throughout the study.
Women of child bearing potential must have a negative serum pregnancy test, not be nursing, and use acceptable contraception

Exclusion Criteria

Clinically significant abnormal laboratory results
Anticipated liver transplantation
History of multiple drug allergies or intolerance to subcutaneous injections
Active HIV, hepatitis C virus, or hepatitis B virus infection(s)
History of recurrent pancreatitis

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03338816). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.