Clinical trial NCT03338816: ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Hepatic Porphyria
Acute Intermittent Porphyria
Porphyria, Acute Intermittent
Acute Porphyria
Hereditary Coproporphyria (HCP)
Variegate Porphyria (VP)
ALA Dehydratase Deficient Porphyria (ADP)
Keywords: Acute Intermittent Porphyria (AIP)
Acute Hepatic Porphyria (AHP)
Hereditary Coproporphyria (HCP)
Variegate Porphyria (VP)
ALA dehydratase deficient porphyria (ADP) (ALAD)
RNAi therapeutic
Porphyria
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-11-09
Enrollment: 94
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
timeFrame: 6 months
Secondary outcomes:
measure: The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP
timeFrame: 3 and 6 months
measure: The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP
timeFrame: 6 months
measure: Annualized Rate of Hemin Administration in Participants With AIP
timeFrame: 6 months
measure: Annualized Rate of Porphyria Attacks in Participants With AHP
timeFrame: 6 months
measure: 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
timeFrame: Baseline and 6 months
measure: 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
timeFrame: Baseline and 6 months
measure: 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
timeFrame: Baseline and 6 months
measure: 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
timeFrame: Baseline and 6 months
measure: AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
timeFrame: Baseline and 6 months
measure: Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
timeFrame: Baseline and 6 months
measure: Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Trial Site
state: Arkansas
city: San Francisco
country: United States
facility: Clinical Trial Site
state: California
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Clinical Trial Site
state: Michigan
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Winston-Salem
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Galveston
country: United States
facility: Clinical Trial Site
state: Texas
city: Salt Lake City
country: United States
facility: Clinical Trial Site
state: Utah
city: Seattle
country: United States
facility: Clinical Trial Site
state: Washington
city: Parkville
country: Australia
facility: Clinical Trial Site
state: Victoria
city: Auchenflower
country: Australia
facility: Clinical Trial Site
city: Camperdown
country: Australia
facility: Clinical Trial Site
city: Sofia
country: Bulgaria
facility: Clinical Trial Site
city: Edmonton
country: Canada
facility: Clinical Trial Site
city: Odense
country: Denmark
facility: Clinical Trial Site
city: Helsinki
country: Finland
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Chemnitz
country: Germany
facility: Clinical Trial Site
city: Munich
country: Germany
facility: Clinical Trial Site
city: Modena
country: Italy
facility: Clinical Trial Site
city: Hamamatsu
country: Japan
facility: Clinical Trial Site
city: Iizuka
country: Japan
facility: Clinical Trial Site
city: Tokyo
country: Japan
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Mexico City
country: Mexico
facility: Clinical Trial Site
city: Rotterdam
country: Netherlands
facility: Clinical Trial Site
city: Warsaw
country: Poland
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: El Palmar
country: Spain
facility: Clinical Trial Site
city: Pamplona
country: Spain
facility: Clinical Trial Site
city: Stockholm
country: Sweden
facility: Clinical Trial Site
city: Taichung
country: Taiwan
facility: Clinical Trial Site
city: Taipei city
country: Taiwan
facility: Clinical Trial Site
city: Taoyuan city
country: Taiwan
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Wang B, Ventura P, Takase KI, Thapar M, Cassiman D, Kubisch I, Liu S, Sweetser MT, Balwani M. Disease burden in patients with acute hepatic porphyria: experience from the phase 3 ENVISION study. Orphanet J Rare Dis. 2022 Aug 26;17(1):327. doi: 10.1186/s13023-022-02463-x.
citation: Balwani M, Sardh E, Ventura P, Peiro PA, Rees DC, Stolzel U, Bissell DM, Bonkovsky HL, Windyga J, Anderson KE, Parker C, Silver SM, Keel SB, Wang JD, Stein PE, Harper P, Vassiliou D, Wang B, Phillips J, Ivanova A, Langendonk JG, Kauppinen R, Minder E, Horie Y, Penz C, Chen J, Liu S, Ko JJ, Sweetser MT, Garg P, Vaishnaw A, Kim JB, Simon AR, Gouya L; ENVISION Investigators. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Engl J Med. 2020 Jun 11;382(24):2289-2301. doi: 10.1056/NEJMoa1913147.