Huntington’s Disease antisense oligonucleotide huntingtin lowering (‘gene silencing’) trial: IONIS-HTT-Rx


At a glance

Medicine Drug trial
Blood tests and intrathecal injection (injection into the spinal fluid)
HD assessments; including Motor, Cognitive and Behavioural
Scan Magnetic Resonance Imaging

As of 21 December 2015, Isis Pharmaceuticals changed their name to Ionis Pharmaceuticals. This article has been updated reflect this name change [March 2016].

Please note we are not currently recruiting for this trial at NHNN London. Please contact the HD research team on 0203 108 7483 for more information.


For news updates on the HD gene silencing trial visit HD Buzz.


About the study

This is a research study of an investigational drug – a drug that is still being researched and is not yet approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The purpose of this study is to investigate the safety, tolerability and activity of the investigational drug IONIS-HTTRx in patients with early stage Huntington’s Disease.

Huntington’s Disease (HD) is caused by a mutation in the huntingtin gene. A portion of the code within the gene becomes expanded and subsequently instructs the cells to produce an enlarged version of the huntingtin protein. Mutant huntingtin interferes with cell processes and disrupts the overall function of the cell to cause the symptoms of the disease.

IONIS-HTTRx binds to huntingtin specific genetic material to block the production of the huntingtin protein. Known as an antisense drug (ASO), IONIS-HTTRx binds to huntingtin RNA, telling the cell to destroy it. It is hoped that reducing the levels of the mutant protein in this way will slow or halt disease progression. Research studies with IONIS-HTTRx in animal models of HD have been promising and the next stage is to test the safety of the drug in humans.

For an explanation of ASO drugs and their potential use in the treatment of HD click here.


What is involved?
The drug will be given by injection into the lower back, known as an intrathecal injection (a form of ‘lumbar puncture’) to deliver the drug into the cerebrospinal fluid. Cerebrospinal fluid is a clear liquid that surrounds the brain and spinal cord. Treatment by this method will mean that the antisense drug is most likely to reach the cells of the brain that are affected by the expression of the huntingtin protein.

The trial is “blinded” which means the patient and the trial doctor will not know whether the patient is given IONIS-HTTRx or placebo. The placebo is an injection that does not contain any active drug. Each patient will receive four doses of IONIS-HTTRx or placebo by an intrathecal injection, with doses four weeks apart. After the last dose, patients will be followed for several weeks to monitor the safety and activity of IONIS-HTTRx.
The study period includes a 13-week period during which you receive the study drug, followed by a 15-week observational period. Participants may be required to stay overnight in the medical facility during this time.

Assessments include physiological and neurological examinations and vital sign measurements. Blood and cerebrospinal fluid samples will be collected. MRI scans will also be performed and you will complete several questionnaires and computer and paper based tasks.


Who can take part?

Please note we are not currently recruiting for this trial at NHNN London. Please contact the HD research team on 0203 108 7483 for more information.

The main purpose of this study is to examine the safety of IONIS-HTTRx and only 36-48 patients with early stage Huntington’s Disease will be recruited across all the participating sites. Patients will need to live near a study centre and have a trial partner – someone who is a family member or close friend and can accompany them to trial visits and be familiar with their HD care.

Updated August 13, 2015