- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03338816
ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
May 31, 2022 updated by: Alnylam Pharmaceuticals
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
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).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
94
Phase
- Phase 3
Expanded Access
No longer available outside the clinical trial.
See expanded access record.
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Auchenflower, Australia, 4066
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Camperdown, Australia, 2050
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Victoria
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Parkville, Victoria, Australia, 3050
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Sofia, Bulgaria, 1431
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Edmonton, Canada, T6G 2R3
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Odense, Denmark, 5000
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Helsinki, Finland, 00290
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Paris, France, 75877
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Chemnitz, Germany, 09116
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Munich, Germany, 80331
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Modena, Italy, 41124
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Hamamatsu, Japan, 430-0929
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Iizuka, Japan, 820-8505
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Tokyo, Japan, 108-0073
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Seoul, Korea, Republic of, 05030
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Mexico City, Mexico, 04530
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Rotterdam, Netherlands, 3015
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Warsaw, Poland, 02-776
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Barcelona, Spain, 08036
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El Palmar, Spain, 30120
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Pamplona, Spain, 31008
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Stockholm, Sweden, 171 76
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Taichung, Taiwan, 40705
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Taipei city, Taiwan, 10002
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Taoyuan city, Taiwan, 33305
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London, United Kingdom, SE5 9RS
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Arkansas
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Little Rock, Arkansas, United States, 72205
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California
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San Francisco, California, United States, 94143
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Massachusetts
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Boston, Massachusetts, United States, 02114
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Michigan
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Ann Arbor, Michigan, United States, 48109
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New York
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New York, New York, United States, 10029
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19107
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Texas
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Galveston, Texas, United States, 77555
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Utah
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Salt Lake City, Utah, United States, 84112
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Washington
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Seattle, Washington, United States, 98195
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
10 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Givosiran/Givosiran
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.
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Givosiran by SC
Other Names:
Matching placebo (normal saline [0.9% NaCl]) by SC
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Placebo Comparator: Placebo/Givosiran
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.
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Givosiran by SC
Other Names:
Matching placebo (normal saline [0.9% NaCl]) by SC
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
Time Frame: 6 months
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Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management.
The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
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6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP
Time Frame: 3 and 6 months
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The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels.
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3 and 6 months
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The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP
Time Frame: 6 months
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The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels.
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6 months
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Annualized Rate of Hemin Administration in Participants With AIP
Time Frame: 6 months
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Annualized rate of hemin doses was evaluated as annualized days of hemin use.
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6 months
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Annualized Rate of Porphyria Attacks in Participants With AHP
Time Frame: 6 months
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Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management.
The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
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6 months
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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
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Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain.
Daily eDiary entries were averaged into a weekly (i.e. 7 day) score.
The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score.
Lower scores indicate an improvement.
The 6-month AUC was calculated based on change from baseline in weekly mean scores.
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Baseline and 6 months
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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
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Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain.
Daily eDiary entries were averaged into a weekly (i.e. 7 day) score.
The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score.
Lower scores indicate an improvement.
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Baseline and 6 months
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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
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Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue.
Daily eDiary entries were averaged into a weekly (i.e. 7 day) score.
The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score.
Lower scores indicate an improvement.
The 6-month AUC was calculated based on change from baseline in weekly mean scores.
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Baseline and 6 months
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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
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Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue.
Daily eDiary entries were averaged into a weekly (i.e. 7 day) score.
The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score.
Lower scores indicate an improvement.
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Baseline and 6 months
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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
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Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea.
Daily eDiary entries were averaged into a weekly (i.e. 7 day) score.
The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score.
Lower scores indicate an improvement.
The 6-month AUC was calculated based on change from baseline in weekly mean scores.
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Baseline and 6 months
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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
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Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea.
Daily eDiary entries were averaged into a weekly (i.e. 7 day) score.
The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score.
Lower scores indicate an improvement.
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Baseline and 6 months
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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
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The SF-12 is a survey designed for use in patients with multiple chronic conditions.
This 12-item scale can be used to assess the physical and mental health of respondents.
10 of the 12 questions are answered on a 5 point likert scale and 2 are answered on a 3 point likert scale.
The questions are then scored and weighted into 2 subscales, physical health and mental health.
Respondents can have a score that ranges from 0-100 with 100 being the best score and indicating high physical or mental health.
A 3 point change in SF-12 score reflects a meaningful difference.
A higher score indicates improvement.
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Baseline and 6 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 16, 2017
Primary Completion (Actual)
January 31, 2019
Study Completion (Actual)
May 31, 2021
Study Registration Dates
First Submitted
November 7, 2017
First Submitted That Met QC Criteria
November 7, 2017
First Posted (Actual)
November 9, 2017
Study Record Updates
Last Update Posted (Actual)
June 23, 2022
Last Update Submitted That Met QC Criteria
May 31, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ALN-AS1-003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Clinical Trials on Givosiran
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Alnylam PharmaceuticalsCompletedAcute Intermittent PorphyriaUnited States, United Kingdom, Sweden
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Alnylam PharmaceuticalsCompletedAcute Intermittent PorphyriaUnited States, United Kingdom, Sweden
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Alnylam PharmaceuticalsCompletedPorphyria, Acute Intermittent | Acute Intermittent Porphyria (AIP) | Acute Hepatic Porphyria (AHP) | Acute PorphyriaSweden