Alnylam - ALN-TTR02-004 - TTR Mediated Polyneuropathy (FAP)
Research type
Research Study
Full title
APOLLO: A Phase 3 Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Patisiran (ALN-TTR02) in Transthyretin (TTR)-Mediated Polyneuropathy (Familial Amyloidotic Polyneuropathy-FAP)
IRAS ID
165898
Contact name
Julian Gillmore
Contact email
Sponsor organisation
Alnylam Pharmaceuticals, Inc
Eudract number
2013-002987-17
Clinicaltrials.gov Identifier
117395, IND Number
Duration of Study in the UK
3 years, 2 months, 0 days
Research summary
Transthyretin-mediated amyloidosis (ATTR) is an inherited disease caused by a mutation in the transthyretin (TTR) gene. Transthyretin is a protein secreted predominantly by cells within the liver. Mutations in this protein cause it to form insoluble fibrous deposits in tissues. The particular TTR mutation and sites of the deposit are what determine which body systems the disease affects.
ATTR is a progressive disease associated with severe morbidity, with a life expectancy limited to 5 to 15 years from symptom onset. There are over 100 reported TTR mutations which are associated with 2 clinical syndromes: familial amyloidotic polyneuropathy (FAP) and familial amyloidotic cardiomyopathy (FAC). “Patisiran” is being developed by Alnylam for the treatment of ATTR patients with symptomatic FAP.
Patisiran comprises a small interfering ribonucleic acid which is specific for TTR, and formulated in a hepatotropic lipid nanoparticle (LNP) for intravenous (IV) administration. Following LNP-mediated delivery to the liver, patisiran targets TTR mRNA for degradation, resulting in the potent and sustained reduction of mutant and WT TTR protein via the RNAi mechanism. Since circulating TTR is almost exclusively synthesized in the liver, the IV administration of patisiran is postulated to reduce the level of precursors that lead to amyloid fibril deposition, resulting in clinical benefit to patients with FAP.
Previous experience, suggest that lowering the circulating amyloidogenic protein by at least 50% is required to impact the clinical course of the disease, with reductions beyond 50% providing further improvement in outcomes. It is therefore thought that the >80% suppression in both WT and mutant TTR observed upon administration of 0.3 mg/kg patisiran once every 21 days will result in clinical benefit in FAP patients.
This is a global, multicentre study. Approximately 200 patients (males and females aged 18 and 85 years) that have FAP will be recruited in the study.REC name
London - Hampstead Research Ethics Committee
REC reference
14/LO/2035
Date of REC Opinion
18 Dec 2014
REC opinion
Further Information Favourable Opinion