Phase 4 Trial Will Test if Ocrevus Can Prevent MS Onset in RIS Patients
Yale University is launching CELLO, a multicenter study to investigate the efficacy of Ocrevus (ocrelizumab) in treating people with lesions suggestive of multiple sclerosis (MS), a condition known as radiologically isolated syndrome.
The Phase 4 study (NCT04877457) aims to evaluate whether short-term treatment with Ocrevus can delay or prevent the onset of MS in radiologically isolated syndrome (RIS) patients. These patients have no evident neurological MS symptoms, but MRI scans show disease-related brain and/or spinal cord lesions.
In a global study, over 50% of people diagnosed with RIS, which has no approved treatments, were found to develop MS within 10 years.
“CELLO will be one of the first studies to systematically examine whether short-term immunologic intervention is a viable option,” Erin Longbrake, MD, PhD, said in a university press release. Longbrake is an assistant professor of neurology at Yale School of Medicine and this trial’s global principal investigator.
Genentech, a member of the Roche Group that developed and markets Ocrevus, an approved disease-modifying MS therapy, is a study collaborator.
CELLO is expected to open in July, and will be a randomized and placebo-controlled trial, with patients assigned either to Ocrevus or to a matched placebo as a control group. Up to 100 adults, ages 18 to 40, with an established RIS diagnosis within the previous five years (or lesion accumulation within five years) are to be enrolled at 20 worldwide sites. General contact information is available here.
Treatment efficacy, a main trial goal, will be measured by the time from study start (baseline) — out to four years — that patients in the Ocrevus group, relative to controls, progress to new radiological or clinical evidence of MS. Radiological evidence will come through scans showing new brain/spinal cord lesions, and clinical events are defined as neurological symptoms linked to demyelination — the loss the protective myelin coating of nerve fibers that marks this disease.
Patients will be followed for up to seven years, the release states.
Ocrevus is an anti-CD20 monoclonal antibody that targets mature B-cells in the immune system. The majority of mature B-cells express the CD20 protein on their surface, and studies suggest that CD20-positive B-cells attack myelin, leading to immune reactions that can cause MS symptoms and disability. Ocrevus works to deplete these B-cells.
It is approved in both the U.S. and the EU to treat relapsing forms of MS and primary progressive MS (PPMS). Multiple clinical trials continue to evaluate various aspects of the therapy’s efficacy and safety.
CELLO researchers will also conduct in-depth immunological analyses of the blood and cerebrospinal fluid — the fluid that surrounds the brain and spinal cord — collected from Ocrevus-treated patients. A trial goal is to develop potential biomarkers that can predict response to therapy and might prevent MS recurrence.
“CELLO moves us in an important direction with the early treatment of patients with MS to prevent disease onset,” said David Hafler, MD, a professor of neurology and immunobiology at Yale.