Study on an Investigational Drug, Givosiran, for the Treatment of Acute Hepatic Porphyrias
- Conditions
- Acute Hepatic Porphyrias (AHP)MedDRA version: 20.0Level: PTClassification code 10036182Term: Porphyria acuteSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 20.0Level: LLTClassification code 10036184Term: Porphyria hepaticSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2017-002432-17-PL
- Lead Sponsor
- Alnylam Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 74
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 copropohyrinogen 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
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
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method