A Phase 3b Study of Patisiran-LNP in Patients with hATTR Amyloidosis
Research type
Research Study
Full title
An Open-label Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of Patisiran-LNP in Patients with Hereditary Transthyretin-mediated Amyloidosis (hATTR amyloidosis) with Disease Progression Post-Orthotopic Liver Transplant
IRAS ID
254535
Contact name
Julian Gillmore
Contact email
Sponsor organisation
Alnylam Pharmaceuticals, Inc.
Eudract number
2018-003519-24
Duration of Study in the UK
1 years, 10 months, 0 days
Research summary
hATTR amyloidosis is an inherited, rare, life-threatening disease. It is caused by mutations in the transthyretin (TTR) gene that result in misfolded TTR proteins accumulating as amyloid fibrils in multiple sites, including the nerves, heart and gastrointestinal tract. Patients with this condition usually have heart problems and symptoms such as muscle weakness in the limbs and, at later stages, inability to walk, problems affecting the stomach and the gut (leading to malnutrition), and bladder dysfunction. hATTR amyloidosis is more frequent in men than women. Alnylam Pharmaceuticals, the sponsor of this study, has developed a medication to treat hATTR amyloidosis patients called patisiran-LNP. Patisiran-LNP has now been granted marketing authorisation in the EU and US under the brand name 'Onpattro™'.
Patisiran-LNP is a small interfering ribonucleic acid (siRNA) which is specific for TTR. It has been designed to reduce both mutant and normal TTR production in the liver and therefore prevent the formation of amyloid deposits.
As the liver is the primary source of the TTR protein, liver transplants are used in some patients to treat hATTR amyloidosis patients. Transplantation removes the mutated protein from the circulation however normal TTR is produced by the transplanted liver. Approximately one-third of hATTR amyloidosis patients experience disease progression following transplant and therefore there is a need for a safe and effective treatment in this subset of hATTR amyloidosis patients. The proposed study is designed to evaluate the safety, efficacy and pharmacokinetics (the impact of the body on the drug)of patisiran-LNP in patients with hereditary ATTR amyloidosis with disease progression after liver transplant.
This is a global, multicentre, phase 3b, open-label study which will recruit 20 adult participants at approximately 10 different study sites in Europe.
REC name
London - London Bridge Research Ethics Committee
REC reference
19/LO/0134
Date of REC Opinion
12 Mar 2019
REC opinion
Further Information Favourable Opinion