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

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ClinicalTrials.gov Identifier: NCT03338816
Recruitment Status : Active, not recruiting
First Posted : November 9, 2017
Last Update Posted : October 8, 2018
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

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).

Condition or disease Intervention/treatment Phase
Acute Hepatic Porphyria Acute Intermittent Porphyria Porphyria, Acute Intermittent Acute Porphyria Hereditary Coproporphyria (HCP) Variegate Porphyria (VP) ALA Dehydratase Deficient Porphyria (ADP) Drug: Givosiran Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
Experimental: Givosiran Drug: Givosiran
by subcutaneous (SC) injection

Placebo Comparator: Placebo
Normal Saline (0.9% NaCl)
Drug: Placebo
Sterile Normal Saline (0.9% NaCl)




Primary Outcome Measures :
  1. The annualized rate of porphyria attacks in patients with AIP. [ Time Frame: at 6 months ]

Secondary Outcome Measures :
  1. The pharmacodynamic (PD) effect of Givosiran on urine levels of delta-aminolevulinic acid (ALA) in patients with AIP. [ Time Frame: at 3 and 6 months ]
  2. The pharmacodynamic (PD) effect of Givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP. [ Time Frame: at 6 months ]
  3. Annualized rate of hemin administrations in AIP patients. [ Time Frame: through month 6 ]
  4. Annualized rate of porphyria attacks in patients with AHP. [ Time Frame: through month 6 ]
  5. Pain as measured by the Brief Pain Inventory-Short Form numeric rating scale, a 0 to 10 point scale with 10 rated as worst pain. [ Time Frame: through month 6 ]
  6. Nausea as measured by the numeric rating scale, a 0 to 10 point scale with 10 rated as worst nausea. [ Time Frame: through month 6 ]
  7. Fatigue as measured by the Brief Fatigue Inventory-Short Form numeric rating scale, a 0 to 10 point scale with 10 rated as worst fatigue. [ Time Frame: through month 6 ]
  8. Change from baseline in the Physical Component Summary of the 12-Item Short Form Survey (SF-12). [ Time Frame: through month 6 ]


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 12 years of age
  • Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, ALA dehydratase deficient porphyria)
  • Elevated urinary or plasma 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03338816


  Hide Study Locations
Locations
United States, Arkansas
Clinical Trial Site
Little Rock, Arkansas, United States, 72205
United States, California
Clinical Trial Site
San Francisco, California, United States, 94143
United States, Florida
Clinical Trial Site
Miami, Florida, United States, 33136
United States, Massachusetts
Clinical Trial Site
Boston, Massachusetts, United States, 02114
United States, Michigan
Clinical Trial Site
Ann Arbor, Michigan, United States, 48109
United States, New York
Clinical Trial Site
New York, New York, United States, 10029
United States, North Carolina
Clinical Trial Site
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
Clinical Trial Site
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Clinical Trial Site
Galveston, Texas, United States, 77555
United States, Utah
Clinical Trial Site
Salt Lake City, Utah, United States, 84112
United States, Washington
Clinical Trial Site
Seattle, Washington, United States, 98195
Australia, Victoria
Clinical Trial Site
Parkville, Victoria, Australia, 3050
Australia
Clinical Trial Site
Auchenflower, Australia, 4066
Clinical Trial Site
Camperdown, Australia, 2050
Belgium
Clinical Trial Site
Leuven, Belgium, 3000
Bulgaria
Clinical Trial Site
Sofia, Bulgaria, 1431
Canada
Clinical Trial Site
Edmonton, Canada, T6G 2R3
Clinical Trial Site
Montréal, Canada, H3A 2B4
Denmark
Clinical Trial Site
Odense, Denmark, 5000
Finland
Clinical Trial Site
Helsinki, Finland, 00290
France
Clinical Trial Site
Paris, France, 75877
Germany
Clinical Trial Site
Chemnitz, Germany, 09116
Clinical Trial Site
Munich, Germany, 80331
Italy
Clinical Trial Site
Milano, Italy, 20122
Clinical Trial Site
Modena, Italy, 41124
Japan
Clinical Trial Site
Hamamatsu, Japan, 430-0929
Clinical Trial Site
Hiroshima, Japan, 734-8551
Clinical Trial Site
Iizuka, Japan, 820-8505
Clinical Trial Site
Tokyo, Japan, 108-0073
Korea, Republic of
Clinical Trial Site
Seoul, Korea, Republic of, 05030
Mexico
Clinical Trial Site
Mexico City, Mexico, 04530
Netherlands
Clinical Trial Site
Rotterdam, Netherlands, 3015
Poland
Clinical Trial Site
Warsaw, Poland, 02-776
Spain
Clinical Trial Site
Barcelona, Spain, 08036
Clinical Trial Site
El Palmar, Spain, 30120
Clinical Trial Site
Pamplona, Spain, 31008
Sweden
Clinical Trial Site
Stockholm, Sweden, 171 76
Switzerland
Clinical Trial Site
Zürich, Switzerland, 8063
Taiwan
Clinical Trial Site
Taichung, Taiwan, 40705
Clinical Trial Site
Taipei city, Taiwan, 10002
Clinical Trial Site
Taoyuan city, Taiwan, 33305
United Kingdom
Clinical Trial Site
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
Study Director: Amy Simon, MD Alnylam Pharmaceuticals

Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03338816     History of Changes
Other Study ID Numbers: ALN-AS1-003
First Posted: November 9, 2017    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alnylam Pharmaceuticals:
Acute Intermittent Porphyria (AIP)
Acute Hepatic Porphyria (AHP)
Hereditary Coproporphyria (HCP)
Variegate Porphyria (VP)
ALA dehydratase deficient porphyria (ADP) (ALAD)
RNAi therapeutic
Porphyria

Additional relevant MeSH terms:
Porphyrias
Porphyria, Erythropoietic
Porphyria, Acute Intermittent
Porphyrias, Hepatic
Coproporphyria, Hereditary
Porphyria, Variegate
Metabolic Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Liver Diseases
Digestive System Diseases