Results Reported from Innovative “MS-SMART” Clinical Trial in Secondary Progressive MS Presented at ECTRIMS

  • Dr. Jeremy Chataway (University College London) presented first results of the MS-SMART Trial at the ECTRIMS conference in Berlin.
  • MS-SMART is an innovative phase 2 clinical trial that compared three potential therapies against placebo to determine their ability to slow brain atrophy (shrinkage) in people with secondary progressive MS.
  • A total of 445 individuals in the United Kingdom with secondary progressive MS were enrolled in the 96-week trial. Each was randomly assigned to receive amiloride, fluoxetine, riluzole, or placebo. The therapies each target different pathways thought to contribute to progressive tissue damage and worsening (progression) in MS. They are also FDA-approved for treating other conditions.
  • Although none of the therapies slowed brain atrophy, the results confirm the feasibility of this innovative multi-arm trial design, enabling much quicker assessments of potential therapies for progressive MS in the future.
  • The clinical trial was investigator-initiated and funded by University College London and multiple other sponsors and agencies including the UK Multiple Sclerosis Society and the National Multiple Sclerosis Society (USA).

“While these results are disappointing, well-controlled trials such as the MS-SMART trial will help inform new approaches for future studies aimed at treating progressive forms of multiple sclerosis. Lessons from this study and others will inform the Alliance’s research priorities and those of other international research funders such as the UK MS Society and National MS Society.”

Prof. Alan Thompson, Chair of the Alliance’s Scientific Steering Committee and Dean of University College London’s Faculty of Brain Sciences

“While the SMART trial did not yield the results I’d hoped for, I am very grateful as this trial, together with additional progressive MS research will speed us toward shorter, and faster (simultaneous) clinical trials. There is a hidden benefit to this apparent failure – scarce resources can now be focused on therapies that show more promise. All of us living with progressive MS benefit from such trials, from the courage of these researchers and the science behind them."

Alexis Donnelly, a computer scientist from Dublin and member of the Alliance’s Scientific Steering Committee living with progressive MS for more than 25 years

Background

There are few therapies that have shown benefits for people living with secondary progressive multiple sclerosis, a stage of MS that follows an initial relapsing-remitting course in which there is a progressive worsening of neurologic function and accumulation of disability over time. Because progression usually occurs over many years, there is a need for innovative clinical trial designs that can accelerate the testing of more therapies for their potential to protect the nervous system from harm and slow or stop progression.

Dr. Jeremy Chataway (University College London) and colleagues set out to conduct an innovative, multi-arm trial that would permit testing of three oral drugs at the same time, all of which had shown promising neuroprotective properties. Amiloride is a drug used to treat high blood pressure; fluoxetine is a treatment for depression; and riluzole is a treatment for ALS (motor neuron disease). Each of these are approved by the U.S. Food and Drug Administration for other conditions. This was also the first time that a multi-arm trial was attempted in progressive MS.

The Trial

A total of 445 individuals in the United Kingdom with secondary progressive MS were enrolled in the 96-week trial. Each was randomly assigned to receive amiloride, fluoxetine, riluzole, or placebo, and the participants and healthcare professionals were not aware of their assignment. The main outcome measure was percentage brain volume change from the beginning of the study to the end, measured with MRI imaging. Additional outcomes were measured, including numbers of new or enlarging MS brain lesions; cognitive tests; physician and patient perceptions of effectiveness; and confirmation of whether the multi-arm strategy was successful.

Results

At 96 weeks, none of the drugs showed evidence of slowing brain atrophy or other significant benefits. However, the results confirm the feasibility of this innovative multi-arm phase 2 trial design, which in the future will likely enable much quicker assessments of potential therapies for progressive MS. This work also helps rule out these three potential treatments for progressive MS.

Dr. Chataway reported results on October 12, 2018 at the meeting of the European Committee for Treatment and Research into Multiple Sclerosis (ECTRIMS) in Berlin. The clinical trial was investigator-initiated and funded by University College London and multiple other sponsors and agencies including the UK Multiple Sclerosis Society and the National Multiple Sclerosis Society (USA). Other sponsors included the University College London, the Efficacy and Mechanism Evaluation Programme, Medical Research Council, and managed by the National Institute for Health Research.

 

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