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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03338816




Registration number
NCT03338816
Ethics application status
Date submitted
7/11/2017
Date registered
9/11/2017

Titles & IDs
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
Secondary ID [1] 0 0
ALN-AS1-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Hepatic Porphyria 0 0
Acute Intermittent Porphyria 0 0
Porphyria, Acute Intermittent 0 0
Acute Porphyria 0 0
Hereditary Coproporphyria (HCP) 0 0
Variegate Porphyria (VP) 0 0
ALA Dehydratase Deficient Porphyria (ADP) 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Givosiran
Treatment: Drugs - Placebo

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.

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.


Treatment: Drugs: Givosiran
Givosiran by SC

Treatment: Drugs: Placebo
Matching placebo (normal saline \[0.9% NaCl\]) by SC
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP
Timepoint [1] 0 0
3 and 6 months
Secondary outcome [2] 0 0
The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Annualized Rate of Hemin Administration in Participants With AIP
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Annualized Rate of Porphyria Attacks in Participants With AHP
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline and 6 months
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline and 6 months
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Baseline and 6 months
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Baseline and 6 months
Secondary outcome [9] 0 0
AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
Timepoint [9] 0 0
Baseline and 6 months
Secondary outcome [10] 0 0
Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
Timepoint [10] 0 0
Baseline and 6 months
Secondary outcome [11] 0 0
Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP
Timepoint [11] 0 0
Baseline and 6 months

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/05/2021
Sample size
Target
Accrual to date
Final
94
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Clinical Trial Site - Parkville
Recruitment hospital [2] 0 0
Clinical Trial Site - Auchenflower
Recruitment hospital [3] 0 0
Clinical Trial Site - Camperdown
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sofia
Country [12] 0 0
Canada
State/province [12] 0 0
Edmonton
Country [13] 0 0
Denmark
State/province [13] 0 0
Odense
Country [14] 0 0
Finland
State/province [14] 0 0
Helsinki
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Germany
State/province [16] 0 0
Chemnitz
Country [17] 0 0
Germany
State/province [17] 0 0
Munich
Country [18] 0 0
Italy
State/province [18] 0 0
Modena
Country [19] 0 0
Japan
State/province [19] 0 0
Hamamatsu
Country [20] 0 0
Japan
State/province [20] 0 0
Iizuka
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Mexico
State/province [23] 0 0
Mexico City
Country [24] 0 0
Netherlands
State/province [24] 0 0
Rotterdam
Country [25] 0 0
Poland
State/province [25] 0 0
Warsaw
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Spain
State/province [27] 0 0
El Palmar
Country [28] 0 0
Spain
State/province [28] 0 0
Pamplona
Country [29] 0 0
Sweden
State/province [29] 0 0
Stockholm
Country [30] 0 0
Taiwan
State/province [30] 0 0
Taichung
Country [31] 0 0
Taiwan
State/province [31] 0 0
Taipei city
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taoyuan city
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alnylam Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Alnylam Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.

Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03338816