Acute hepatic porphyrias
Conditions
Interventions
Monthly Givosiran/Placebo 2.5mg/kg subcutaneously administered during the
blinded 6 month treatment period
Monthly Givosiran 1.25 mg/kg or 2.5mg/kg subcutaneously administered during the
open-label
Sponsors
Alnylam Pharmaceuticals
Eligibility
Age
12 Years to 99 Years
Inclusion 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 *4x 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 hydroxmethylbilane synthase gene (HMBS; also referred to as the porphobilibnogen 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 (
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: * Alanine aminotransferase (ALT) >2xULN * Total bilirubin >&.5xULN. Patients with elevated total bilirubin that is secondary to documented Gilbert's syndrome are eligible if the total bilirubin is 1.5 (patients on an anticoagulant [eg. warfarin] with an INR
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Annualized rate of porphyria attacks requiring hospitalization, urgent healthcare visit, or home hemin administration during the 6-month double-blind treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary All secondary endpoints will be measured over the 6-month double-blind treatment period *Percentage change from baseline in urinary ALA levels *Percentage change from baseline in urinary PBG levels *Annualized number of administered hemin doses *Attack-free days (days without porphyria attacks requiring hospitalization, urgent healthcare visit or home hemin administration) *Daily worst pain score as measured by Brief Pain Inventory-Short Form (BPI-SF) numeric rating scale (NRS) *Daily worst nausea score as measured by NRS *Daily worst fatigue score as measured by Brief Fatigue Inventory - Short Form (BFI-SF) NRS *Change from baseline in the Physical Component Summary (PCS) of the 12-item Short-Form Health Survey (SF-12) | — |
Countries
Netherlands
Outcome results
None listed