A Phase 3 clinical trial is enrolling adults with Huntington’s disease across the United States and Canada to test the potential of the investigational therapy RG6042.
RG6042, formerly known as IONIS-HTTRx, is an investigative antisense oligonucleotide treatment that was initially developed by Ionis Pharmaceuticals and later on acquired by Roche (also known as Genentech in the U.S.). It is designed to target and destroy all forms of mutant huntingtin protein (mHTT) — the underlying cause of Huntington’s — potentially delaying or stopping disease progression.
“We are pleased that RG6042 has progressed to a Phase 3 study,” Brett P. Monia, PhD, COO of Ionis, said in a press release. “Enrollment of the first patient in this pivotal trial represents substantial hope for people living with Huntington’s disease and their families.”
The trial will take place at 20 sites in the U.S. and six in Canada, and Roche plans for sites to open in other countries, including the U.K. and Germany. Patients will be randomly assigned to receive RG6042 or a placebo, injected directly into the spinal canal (intrathecal administration), once a month or once every two months for about two years.
Researchers will evaluate treatment safety and efficacy, and monitor any changes in the severity of symptoms, disease progression course, motor and cognitive function, and behavioral manifestations.
All participants who complete the GENERATION HD1 study may be able to enroll in an open-label (no placebo group) extension trial and be treated with RG6042. This long-term study is pending approval from authorities and ethics committees, and additional data supporting RG6042’s continued development.
Results from a previous Phase 1/2 trial (NCT02519036) in 46 adults with early-stage Huntington’s showed, for the first time, that RG6042 could effectively reduce the levels of mHTT in the cerebral spinal fluid by up to 60%. This difference corresponds to an estimated 55% to 85% reduction of mHTT in the cortex (the outermost layer), and 20% to 50% in the caudate (a deep region) of the brain.
The results of the GENERATION HD1 trial are expected to support regulatory requests that RG6042 be approved to treat people with Huntington’s.
RG6042 was given a priority medicine (PRIME) designation by the European Medicines Agency in August 2018 as a potential Huntington’s treatment. The designation is expected to support the therapy’s clinical development and to expedite its regulatory review and approval.
Detailed information about the study is available in a webinar by the Huntington’s Disease Society of America.