Trial Will Test Mavenclad for Advanced Progressive MS
After some delays due to the COVID-19 pandemic, the Phase 2/3 clinical trial evaluating whether Mavenclad (cladribine) can slow hand and arm function worsening in adults with progressive multiple sclerosis (MS) and very limited walking abilities, has recruited its first patient.
The study, ChariotMS (NCT04695080), aims to enroll up to 200 patients with advanced progressive MS — a population typically excluded from clinical trials — at 20 sites across the U.K. More information about contacts and locations is available here.
“The recruitment of our first participant is a huge milestone, and I can hardly describe how excited I am that ChariotMS is finally getting underway in earnest,” Klaus Schmierer, PhD, the trial’s principal investigator of the Queen Mary University of London and Barts Health NHS Trust, said in a press release of MS Society UK, which is partly funding the study.
While maintaining MS patients’ upper limb function “is essential to their quality of life,” until now “walking ability has been the only official measurement of whether or not an MS treatment is effective” in clinical trials, Schmierer added.
“This has excluded people who depend on a wheelchair from taking part in trials and, as a result, from accessing effective treatment that will help maintain their hand and arm function,” Schmierer explained.
He believes that, if successful, ChariotMS “would be a major step towards a first DMT [disease-modifying therapy] to protect upper limb function for people with MS who aren’t able to use their lower limbs at all, or can only walk short distances with help from aids like crutches.”
Developed by EMD Serono (Merck KGaA outside North America), Mavenclad is an oral treatment that works by killing the immune cells that drive the abnormal immune attacks and inflammation in MS patients’ nervous system.
While inflammation was historically thought to play less of a role in advanced MS than in earlier stages of disease, increasing evidence is challenging this idea, supporting interest in using DMTs like Mavenclad in people with advanced disease.
The EMD Serono-funded ChariotMS study will investigate whether Mavenclad is superior to placebo at slowing hand and arm function decline in adults at advanced stages of either primary or secondary progressive MS.
Besides EMD Serono and MS Society U.K., the trial also is being supported by government agencies, and other charities, including the Barts Charity, also in the U.K., and the National MS Society, in the U.S.
Eligible patients must have Expanded Disability Status Scale (EDSS) scores between 6.5 and 8.5 — meaning they are unable to walk more than 20 meters (about 65 feet) using two crutches, or can’t walk at all, but still retain some function in their arms and hands.
Participants will be assigned randomly to receive weight-adjusted oral tablets of either Mavenclad or placebo, once a day for two short treatment periods of eight to 10 days, separated by one year.
The study’s main goals are to assess changes in the Nine Hole Peg Test, a measure of finger dexterity, after two years and the proportion of patients not showing upper limb function worsening in the test.
Secondary goals include changes in other validated measures of hand and arm function, as well as in walking ability, vision, cognitive function, fatigue, work productivity and activity, quality of life, brain and spinal cord lesions, and safety measures.
After several failed attempts to enroll MS clinical trials, Carol Allen, a 70-year-old painter from Bromley, was the first patient to officially join the ChariotMS study. She has lived with primary progressive MS for more than 20 years, and uses a wheelchair to get around.
“I’ve got three grown-up children and six grandchildren, so it’s really important that I can continue being able to go out and do things with them,” Allen said, noting that maintaining hand and arm function would make all the difference.
“It would help me with the basic stuff, like transferring to and from my wheelchair, but would also allow me to continue enjoying the nicer things in life,” such as painting, one of her “biggest passions.”
While neither Allen nor the investigators will know whether she was assigned Mavenclad or a placebo until the end of the trial, expected by mid-2024, her participation will help to find out whether Mavenclad has the potential to one day become the first approved DMT for advanced MS.
“If it helps me then great, but if it helps people after me, that’s great too,” Allen said.
Clare Walton, PhD, head of research at MS Society UK, said that “living with MS can be relentless, painful and disabling, and as the condition progresses treatment options become limited, or even non-existent.”
“This can leave people with progressive forms of MS feeling written off and hopeless,” Walton said, adding that “finding a treatment to protect hand and arm function would give hope to many people with MS, helping them to maintain independence and improve their quality of life immensely.”
“We are so proud to be supporting this ground-breaking trial, which will help bring us closer than ever to our goal of finding treatments for everyone with MS,” Walton said.