Single Ascending Doses of ALN-TTR02 in Healthy Volunteers

• Research type

  Research Study

• Full title

  A Phase 1, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of ALN-TTR02 in Healthy Volunteers

• IRAS ID

  98963

• Contact name

  Joseph Chiesa

• Sponsor organisation

  Alnylam Pharmaceuticals, Inc

• Eudract number

  2011-005291-42

• ISRCTN Number

  N/a

• Clinicaltrials.gov Identifier

  N/a

• Research summary

  ALN-TTR02-001 is being developed to lower both normal and abnormal transthyretin (TTR) protein levels and reduce the amount of amyloid formed in the body. Large deposits of amyloid causes damage to organs such as the heart and nerves, leading to a fatal disease called transthyretin -mediated amyloidosis (ATTR). ATTR is associated with clinical conditions such as the familial amyloidotic polyneuropathy and familial amyloidotic cardiomyopathy. It is estimated that 45 000 to 50 000 people individuals suffer from these conditions which causes severe morbidity and mortality, with a life expectancy of 5 to 15 years from symptom onset. In the large majority of patients who do not qualify for liver transplantation or treatment with tafamidis (drug recently approved in Europe), the disease is primarily managed with palliative care. ALN-TTR02-001 is being formulated as a solution for injection which contains a small interfering ribonucleic acid (siRNA) molecule packaged inside a tiny, fat-containing particle (lipid nanoparticle). The small size and low surface charge on these nanoparticles allows it to pass through the blood vessel walls of the liver. This enables targeted breakdown of mRNA (the chemical the cells use to produce proteins from genes) and a consequent reduction in the target protein levels. The ability to selectively and potently breakdown the mRNA encoding the TTR protein, using the small interfering ribonucleic acid (siRNA), offers an effective and precise approach for the treatment of ATTR. ALN-TTR02-001 is intended for administration as an IV infusion over 1 hour. This is a single ascending dose study in up to 8 sequential cohorts of healthy volunteers. Only the subjects will be blinded to treatment. Each cohort will comprise of 4 subjects randomly assigned to receive the study drug or the placebo. The subjects have a one in four chance of receiving a placebo. All subjects can only take part in one treatment group. All subjects will receive pre-medication prior to intravenous dosing on Day 0. Subjects will be discharged from the unit 4 days after the dose administration and will return to the unit for outpatient visits.

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  12/SC/0082

• Date of REC Opinion

  6 Mar 2012

• REC opinion

  Further Information Favourable Opinion