ALN-TTRSC04-001
Research type
Research Study
Full title
A Phase 1, Randomized, Double-Blind, Placebo Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-TTRSC04 in Healthy Subjects
IRAS ID
1006510
Contact name
Joanne Bailey
Contact email
Sponsor organisation
Alnylam Pharmaceuticals Inc
Clinicaltrials.gov Identifier
Research summary
This study will evaluate if ALN-TTRSC04, is safe when administered to healthy volunteers. Transthyretin (ATTR ) amyloidosis is a rare, serious disease caused by changes in protein transthyretin (TTR). These changes can be caused by genetic variants (hereditary (h) ATTR amyloidosis) or aging (wild-type (wt) ATTR amyloidosis). The liver is the main producer of TTR. TTR can misfold to form a different protein shape called fibrils. Fibrils can form amyloid deposits, which affect the function of major organs. Most common effects of ATTR amyloidosis are heart failure (cardiomyopathy) and nerve damage (polyneuropathy).
Reducing the production of both hATTR and wtATTR in the liver reduces the amount of amyloid that is available to deposit in the organs. Patisiran and vutrisiran are currently approved for the treatment of patients with hATTR amyloidosis with polyneuropathy; studies in patients with ATTR amyloidosis with cardiomyopathy are ongoing. Like patisiran and vutrisiran, ALN-TTRSC04is a ribonucleic acid interference (RNAi) molecule, made up of small pieces of genetic material, that act to inhibit TTR production in the liver. Because ALN-TTRSC04 has the potential to sustain TTR reduction, ALN-TTRSC04 may be given less frequently than patisiran and vutrisiran.
The study is being done to understand whether a reduction in TTR occurs with a single dose of ALN-TTRSC04 compared to placebo (inactive substance, like saline). In this double-blind study, neither the study doctor nor participants know which treatment they receive. Participants will have a 3:1 chance to receive ALN-TTRSC04 or placebo via a single dose injection under the skin. Participants will be given different dose levels from 5mg to 1200mg. This study will look at the safety, tolerability, pharmacokinetics (what the body does to the medication) and pharmacodynamics (what the medications does to the body) of the IMP. 132 healthy volunteers are expected to be enrolled. The duration is approx. 20 months
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
22/SC/0353
Date of REC Opinion
13 Dec 2022
REC opinion
Further Information Favourable Opinion