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

Alnylam Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: ALA Dehydratase Deficient Porphyria (ADP); Variegate Porphyria (VP); Porphyria, Acute Intermittent; Hereditary Coproporphyria (HCP); Acute Porphyria; Acute Intermittent Porphyria; Acute Hepatic Porphyria

Treatments: Drug: Placebo; Drug: Givosiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT03338816

ALN-AS1-003

Details and patient eligibility

About

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).

Enrollment: 94 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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94 participants in 2 patient groups, including a placebo group

Givosiran/Givosiran

Experimental group

Description:

Givosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period.

Treatment:

Drug: Givosiran

Drug: Placebo

Placebo/Givosiran

Placebo Comparator group

Description:

Matching placebo (normal saline \[0.9% NaCl\]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period.

Treatment:

Drug: Givosiran

Drug: Placebo