Alnylam ALN-TTRSC-002
Research type
Research Study
Full title
ALN-TTRSC-002 A Phase 2, Open-Label Trial To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Exploratory Clinical Activity of ALN-TTRSC in Patients with Transthyretin (TTR) Cardiac Amyloidosis
IRAS ID
138798
Contact name
Julian Gillmore
Contact email
Sponsor organisation
Alnylam Pharmaceuticals Inc
Eudract number
2013-002856-33
Research summary
TTR is a protein produced predominantly by hepatocytes (liver cells). Transthyretin related amyloidosis (ATTR) is a disease caused by deposition of TTR amyloid fibrils in various body tissues. Cardiac and neuronal extracellullar deposition of these fibrils culminates in life-threatening cardiomyopathy and/or debilitating neuropathy. Following symptom onset, quality of life is severely impacted and the disease proceeds inexorably to death. Patients are largely managed with supportive care aimed at alleviating heart failure symptoms; there are currently no approved therapies for TTR cardiac amyloidosis and there exists a high unmet need for novel approaches to treatment. RNA interference (RNAi) is a naturally occurring cellular mechanism for regulating gene expression that is mediated by small interfering ribonucleic acids (siRNAs). siRNAs can be designed to target endogenous disease genes. ALN-TTRSC is comprised of a small interfering RNA (siRNA) targeting mutant and wild type TTR mRNA. This would be the first study of ALN-TTRSC in cardiac amyloidosis. The therapeutic hypothesis for this treatment is that lowering of serum TTR protein through inhibition of hepatic production may result in clinical benefit. Support for this approach comes from evidence that lowering of the amyloidogenic protein by >/= 50% improves clinical outcomes in other amyloidotic disorders including AL and AA amyloidosis. Preliminary clinical data shows that doses of ALN-TTRSC up to 10mg/kg have been safe and well-tolerated in healthy volunteers.\n\nAll participants will receive 10 subcutaneous doses of 7.5mg/kg of ALN-TTRSC on an outpatient basis. 5 daily doses will be given during week 1, followed by 5 weekly doses. The study duration would be approximately 16 weeks (over approximately 16 visits) for each participant. Other than 3 MRI scans, all visits/procedures will take place at the National Amyoidosis Centre. Participants will be reimbursed for any expenses incurred in relation to their participation in the study.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
13/EE/0348
Date of REC Opinion
15 Nov 2013
REC opinion
Further Information Favourable Opinion