ISIS-443139-CS1
Research type
Research Study
Full title
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 443139 in Patients with Early Manifest Huntington’s Disease
IRAS ID
174407
Contact name
Sarah Tabrizi
Contact email
Sponsor organisation
Isis Pharmaceuticals, Inc.
Eudract number
2015-000381-66
Duration of Study in the UK
2 years, 5 months, 31 days
Research summary
Huntington's disease is an inherited (genetic) condition that causes damage to cells in the brain over time, affecting movement, awareness, thinking or dementia, judgement and behaviour. It affects relatively young people with an average age of onset of 40 years. Huntington's disease is caused by a faulty gene (HTT) responsible for making a protein called huntingtin. The gene in these patients is bigger than normal and produces a mutant form of huntingtin, causing brain cells to work incorrectly and eventually die.
Currently there's no cure for Huntington's disease. Its progress cannot be reversed or slowed down, although some of the symptoms can be managed with other medications. Death occurs about 15 years after diagnosis.
ISIS Pharmaceuticals Inc. have developed ISIS 443139, an antisense oligonucleotide drug that targets the HTT gene. It lowers the production of huntingtin protein by binding with the mRNA, a molecule that carries the cellular instructions for producing the protein. This drug is the first of its kind to target the faulty gene itself and to try to lower the levels of the toxic protein causing the disease.
Approximately 36 patients (up to a maximum of 48 patients) with a confirmed diagnosis of early stage Huntington’s disease will be assigned to the following groups:
Arm A: 10 mg ISIS 443139 or placebo (3 patients receive ISIS 443139: 1 patient receives placebo)
Arm B: 30mg ISIS 443139 or placebo (6:2)
Arm C: 50mg ISIS 443139 or placebo (6:2)
Arm D: 70mg ISIS 443139 or placebo (12:4)
This is a phase 1/2a multicentre, double blind, randomized, placebo controlled dose escalation study conducted in patients with early manifest HD, which means that neither the patient nor the doctor will be aware of which treatment is received. A proportion of participants will receiving placebo (a drug that has no medical effect).REC name
London - West London & GTAC Research Ethics Committee
REC reference
15/LO/0681
Date of REC Opinion
29 Jul 2015
REC opinion
Further Information Favourable Opinion