ISIS-443139-CS2 - Open label extension study
Research type
Research Study
Full title
An open-label extension study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7234292 (ISIS 443139) in Huntington’s disease patients who participated in prior investigational studies of RO7234292 (ISIS 443139)
IRAS ID
232726
Contact name
Sarah Tabrizi
Contact email
Sponsor organisation
F.Hoffman La-Roche Ltd.
Eudract number
2017-002471-25
Duration of Study in the UK
2 years, 0 months, 0 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, produces a mutant form of huntingtin, causing brain cells to work incorrectly and eventually die.
Currently there's no cure for Huntington's disease. Progress cannot be reversed or slowed down, although some symptoms can be managed with medications. Death occurs about 15 years after diagnosis.
IONIS 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.
This is an open-label extension (OLE) of Study ISIS 443139-CS1. Study ISIS 443139-CS1 was a multiple-ascending dose (MAD) study in 46 patients with early manifest HD aged 25-65 years. In the MAD study, patients received 4 doses of ISIS 443139 or placebo. Eligibility for Study ISIS 443139-CS2 is based on completion of the 4-dose Treatment Period of the prior MAD study. An OLE for the CS1 study was viewed favourably by ethics committees, was part of the informed consent form for the CS1 study and was discussed with all patients at the time of enrolment in the previous study.
Patients will be randomised (Like the flip of a coin) to one of two groups to investigate the safety and tolerability of monthly or quarterly intrathecal (IT) bolus injections of ISIS 443139.REC name
London - West London & GTAC Research Ethics Committee
REC reference
17/LO/1502
Date of REC Opinion
3 Oct 2017
REC opinion
Favourable Opinion