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

• Register: ClinicalTrials.gov
• Last refreshed on: 26 July 2021
• Main ID: NCT03338816
• Date of registration: 07/11/2017
• Prospective Registration: Yes
• Primary sponsor: Alnylam Pharmaceuticals
• Public title: ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
• Scientific title: 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
• Date of first enrolment: November 16, 2017
• Target sample size: 94
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03338816
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Bulgaria, Canada, Denmark, Finland, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Alnylam Pharmaceuticals

Key inclusion & exclusion 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



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acute Intermittent Porphyria

ALA Dehydratase Deficient Porphyria (ADP)

Hereditary Coproporphyria (HCP)

Acute Hepatic Porphyria

Porphyria, Acute Intermittent

Variegate Porphyria (VP)

Acute Porphyria

Intervention(s)

Drug: Placebo

Drug: Givosiran

Primary Outcome(s)

Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) [Time Frame: 6 months]

Secondary Outcome(s)

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 [Time Frame: Baseline and 6 months]

Annualized Rate of Porphyria Attacks in Participants With AHP [Time Frame: 6 months]

Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP [Time Frame: 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 [Time Frame: Baseline and 6 months]

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 [Time Frame: 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 [Time Frame: Baseline and 6 months]

The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP [Time Frame: 6 months]

The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP [Time Frame: 3 and 6 months]

Annualized Rate of Hemin Administration in Participants With AIP [Time Frame: 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 [Time Frame: Baseline and 6 months]

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 [Time Frame: Baseline and 6 months]

Secondary ID(s)

ALN-AS1-003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/02/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03338816