Clinical Trials List
Protocol NumberALN-AS1-003
NCT Number(ClinicalTrials.gov Identfier)NCT03338816
2018-01-31 - 2022-12-31
Phase III
Terminated3
ICD-10E80.0
Hereditary erythropoietic porphyria
ICD-10E80.1
Porphyria cutanea tarda
ICD-10E80.20
Unspecified porphyria
ICD-10E80.21
Acute intermittent (hepatic) porphyria
ICD-10E80.29
Other porphyria
ICD-9277.1
Disorders of porphyrin metabolism
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
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Trial Applicant
MEDPACE TAIWAN LIMITED
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Sponsor
Alnylam Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 施銘洋 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Acute Hepatic Porphyrias (AHP)
Objectives
Primary Objective
Evaluate the effect of SC givosiran, compared to placebo, on the rate of porphyria
attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at
home in patients with AIP
Test Drug
Givosiran (ALN-AS1)
Active Ingredient
ALN-60519
Dosage Form
Solution for Injection
Dosage
189 mg/mL Givosiran
Endpoints
Primary Endpoint
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. See Section 3.5 for the definition of porphyria attacks and associated terms.
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. See Section 3.5 for the definition of porphyria attacks and associated terms.
Inclution Criteria
Inclusion Criteria
Each patient must meet all of the following inclusion criteria to be eligible for enrollment in the
study:
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 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 coporphyrinogen 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 and assent in the case of patients under the age of legal consent, per
local and national requirements
Each patient must meet all of the following inclusion criteria to be eligible for enrollment in the
study:
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 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 coporphyrinogen 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 and assent in the case of patients under the age of legal consent, per
local and national requirements
Exclusion Criteria
Exclusion Criteria
Each patient must not meet any of the following exclusion criteria to be eligible for enrollment in
the study:
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 planned elective major surgery scheduled to occur during 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
Each patient must not meet any of the following exclusion criteria to be eligible for enrollment in
the study:
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 planned elective major surgery scheduled to occur during 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
The Estimated Number of Participants
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Taiwan
10 participants
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Global
74 participants
