Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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21 December 2021 |
Main ID: |
EUCTR2017-002432-17-DE |
Date of registration:
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04/10/2017 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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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 - ENVISION
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Scientific title:
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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 - ENVISION |
Date of first enrolment:
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03/01/2018 |
Target sample size:
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74 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002432-17 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: yes Single blind: Double blind: yes Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Australia
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Belgium
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Bulgaria
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Canada
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Czech Republic
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Denmark
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Finland
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France
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Germany
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Italy
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Japan
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Korea, Republic of
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Mexico
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Netherlands
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Poland
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Spain
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Sweden
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Switzerland
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Taiwan
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United Kingdom
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United States
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Contacts
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Name:
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Regulatory Submissions
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Address:
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5375 Medpace Way
45227
Cincinnati, Ohio
United States |
Telephone:
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+498989 55 718 0 |
Email:
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regsubmissions@medpace.com |
Affiliation:
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Medpace |
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Name:
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Regulatory Submissions
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Address:
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5375 Medpace Way
45227
Cincinnati, Ohio
United States |
Telephone:
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+498989 55 718 0 |
Email:
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regsubmissions@medpace.com |
Affiliation:
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Medpace |
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Key inclusion & exclusion criteria
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Inclusion criteria: 1. Age =12 years 2. Documented diagnosis of AIP, HCP, VP, or ADP based on clinical features (eg, acute attacks of abdominal, back, chest, extremities, and/or limb pain), at least one documented urinary or plasma PBG or ALA value =4× upper limit of normal (ULN) within the past year prior to or during Screening, AND one of the following: • Documented genetic evidence of mutation in a porphyria-related gene, defined as ANY of the following: • AIP: mutation in the hydroxymethylbilane synthase gene (HMBS; also referred to as the porphobilinogen deaminase [PBGD] gene) • HCP: mutation in the coproporphyrinogen oxidase (CPOX) gene • VP: mutation in the protoporphyrinogen oxidase (PPOX) gene • ADP: mutation in the aminolevulinic acid dehydratase (ALAD) homozygous or compound heterozygous genes • OR if the results of a patient’s genetic testing do not identify a mutation in a porphyria-related gene (<5% of cases), a patient may be eligible for the study if they have both clinical features and diagnostic biochemical criteria consistent with AHP (Table 10) 3. Have active disease, with at least 2 porphyria attacks requiring hospitalization, urgent healthcare visit or treatment with IV hemin at home within the 6 months prior to Screening 4. Willing to discontinue and/or not initiate use of prophylactic hemin at the time of Screening and for the duration of the study 5. Have adequate venous access for study sample collection as judged by the investigator 6. Be willing to comply with the contraceptive requirements during the study period, as described in Section 6.4. 7. Be willing and able to comply with the study requirements and to provide written informed consent per local and national requirements. In the case of patients under the age of legal consent, legal guardian(s) must provide written informed consent and the patient should provide assent per local and national requirements and institutional standards. Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria: 1. Any of the following laboratory parameter assessments at Screening: a. Alanine aminotransferase (ALT) >2×ULN b. Total bilirubin >1.5× ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert’s syndrome are eligible if the total bilirubin is <2×ULN c. International normalized ratio (INR) > 1.5 (patients on an anticoagulant [eg, warfarin] with an INR< 3.5 will be allowed) 2. Estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula 3. On an active liver transplantation waiting list, or anticipated to undergo liver transplantation during the blinded study treatment period 4. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or to N-acetylgalactosamine (GalNAc) 5. History of intolerance to subcutaneous injection(s) 6. Known active HIV infection; or evidence of current or chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection 7. Currently enrolled in another investigational device or drug study, or less than 30 days or 5 half-lives (whichever is longer) since ending another investigational device or drug study(s), or receiving other investigational agent(s) 8. Females who are pregnant, breast-feeding, or planning to become pregnant during the study 9. Any condition (eg, medical concern or alcohol or substance abuse), which in the opinion of the Investigator, would make the patient unsuitable for dosing or which could interfere with the study compliance, the patient’s safety and/or the patient’s participation in the 6-month treatment period of the study. This includes significant active and poorly controlled (unstable) cardiovascular, neurologic, gastrointestinal, endocrine, renal or psychiatric disorders unrelated to porphyria identified by key laboratory abnormalities or medical history. 10. History of recurrent pancreatitis, or acute pancreatitis with disease activity within the past 12 months prior to Screening 11. Has a major surgery planned during the first 6 months of the study 12. History of serious infection within one month prior to Screening 13. Had a malignancy within 5 years prior to Screening, except for basal or squamous cell carcinoma of the skin, cervical in-situ carcinoma, or breast ductal carcinoma, that has been successfully treated
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
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Acute Hepatic Porphyrias (AHP) MedDRA version: 20.0
Level: PT
Classification code 10036182
Term: Porphyria acute
System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0
Level: LLT
Classification code 10036184
Term: Porphyria hepatic
System Organ Class: 10010331 - Congenital, familial and genetic disorders
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Intervention(s)
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Product Name: Givosiran Product Code: ALN-AS1 Pharmaceutical Form: Solution for injection INN or Proposed INN: ALN-60519 CAS Number: 1639325-44-2 Current Sponsor code: ALN-60519 Other descriptive name: CAS # in D.3.9.1 for Sodium Salt. CAS number 1639325-43-1 (Parent Acid) Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 189- Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use
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Primary Outcome(s)
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Main Objective: • Evaluate the effect of subcutaneous (SC) givosiran, compared to placebo, on the rate of porphyria attacks requiring hospitalization, urgent healthcare visit, or intravenous (IV) hemin administration at home in patients with acute intermittent porphyria (AIP)
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Timepoint(s) of evaluation of this end point: Over the 6-month treatment period.
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Secondary Objective: • To evaluate the effect of givosiran, compared to placebo, on: o Urinary aminolevulinic acid (ALA) levels in patients with AIP o Urinary porphobilinogen (PBG) levels in patients with AIP o Hemin usage in patients with AIP o The rate of porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home in patients with any AHP o In patients with AIP on the symptoms of pain, nausea, and fatigue o In patients with AIP on the Physical Component Summary (PCS) of the 12-item Short-Form Health Survey (SF-12) • Evaluate the safety and tolerability of givosiran in patients with any AHP
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Primary end point(s): • Annualized rate of porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home in patients with AIP over the 6-month treatment period
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Secondary Outcome(s)
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Timepoint(s) of evaluation of this end point: All secondary endpoints will be measured over the 6-month double-blind treatment period
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Secondary end point(s): • Urinary ALA in patients with AIP at 3 months • Urinary ALA in patients with AIP at 6 months • Urinary PBG in patients with AIP at 6 months • Annualized rate of administered hemin doses in patients with AIP over the 6-month treatment period • Annualized rate of porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home in patients with any AHP over the 6-month treatment period • Daily worst pain score as measured by Brief Pain Inventory-Short Form (BPI-SF) numeric rating scale (NRS) in patients with AIP over the 6-month treatment period • Daily worst nausea score as measured by NRS in patients with AIP over the 6-month treatment period • Daily worst fatigue score as measured by Brief Fatigue Inventory-Short Form (BFI-SF) NRS in patients with AIP over the 6-month treatment period • Change from baseline in the PCS of the SF-12 in patients with AIP at 6 months
Safety • Incidence, severity, seriousness, and relatedness of adverse events during the 6-month treatment period and in the OLE period
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Secondary ID(s)
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126094
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ALN-AS1-003
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2017-002432-17-GB
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NCT03338816
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Source(s) of Monetary Support
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Alnylam Pharmaceuticals, Inc.
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Ethics review
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Status: Approved
Approval date: 03/01/2018
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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