Clinical Trials: The Key to Progress in Treating Pediatric MS

Doctor and young girlIn May 2018, Gilenya® (fingolimod) became the first drug approved by the United States Food and Drug Administration (FDA) to treat multiple sclerosis (MS) in pediatric patients.1 Thousands of researchers and clinicians worked for many years to reach that milestone, but in the end, it was attained by the courage and commitment of 215 young people and their parents.

Those children and adolescents participated in PARADIGMS, a Phase III study that assessed the safety and effectiveness of Gilenya relative to interferon beta-1a2 (given in a dose of 30 ug weekly). The study found that while both medications reduced the relapse rate from patients’ baseline experience, Gilenya cut relapses to a much greater extent than the other agent.2 Further, the study showed that the side effects seen with Gilenya in pediatric patients were similar to those in adults.1

PARADIGMS was a large trial, involving more than 80 study sites in 25 countries. Despite that worldwide scope, it took researchers three years to enroll 215 patients.3 Another international study with 77 sites in 22 countries took 3.5 years to enroll 166 patients.3

Emmanuelle Waubant, MD, says that while several factors pose obstacles to conducting clinical trials in children and adolescents with MS, those challenges must be overcome if pediatric patients are going to benefit from a range of safe, effective therapies. The small size of the pediatric MS population is one of the most significant impediments to trial recruitment, notes Dr. Waubant, a professor of neurology at the University of California, San Francisco (UCSF) and expert in pediatric MS. She explains that there are fewer than 5,000 pediatric MS patients in the United States, and perhaps only 10,000 or so children and adolescents with MS worldwide. Further, because the median age for onset of symptoms in pediatric MS is 15 years, most patients can only participate in pediatric trials for a few years before they reach adulthood.

To help overcome those and other obstacles, the International Pediatric Multiple Sclerosis Study Group (IPMSSG) convened a meeting of 14 pediatric MS experts in New York City in January 2018. As chair of the IPMSSG’s Clinical Trial Task Force, Dr. Waubant led the proceedings. She explains that the goal was to identify study designs and best practices that would generate high-quality evidence on the safety of MS therapies in children and adolescents, and to help remove regulatory and insurance barriers to obtaining treatment.3

The recommendations, which were published in the online version of Neurology this May, include calls for:

  • conducting pediatric pharmacokinetic and pharmacodynamic studies for all new MS therapies for which such testing is feasible to identify the appropriate dose in children
  • avoiding placebo-controlled trials of immunomodulatory agents already proven to be effective in adults
  • allowing open-label studies that focus on safety and pharmacology to be sufficient to approve the pediatric use of an MS therapy that already has been well-studied and approved in adults and that has been shown through analyses to have a strong likelihood of efficacy in children and adolescents
  • when a Phase III, controlled trial is required, employing MRI findings rather than clinical events as the primary endpoint whenever possible, because a strong correlation between the two has been demonstrated and using MRI findings allows for a shorter trial period
  • considering the addition of teenagers to some Phase III trials of investigational MS therapies being assessed in adultss
  • enrolling pediatric MS patients in registries to monitor the long-term safety of medication
  • choosing approaches for testing that minimize inconvenience to patients and their families3

“The aim is to ensure the safety of medications that may be used to treat MS in children and adolescents, but to do so in a way that leverages thoughtful study designs and the large database we have in adult patients,” Dr. Waubant explains.

No matter how innovative its design, however, a study can only be meaningful if enough patients enroll to make its findings statistically reliable. For that reason, Dr. Waubant urges parents and patients to talk with their MS clinician about clinical trials, and to consider participating.

MSAA can also help parents and patients find MS clinical trials. Working in partnership with Antidote, a digital health company, MSAA offers an easy-to-use clinical trial search function on its website, available at


1 U.S. Food and Drug Administration (FDA). FDA expands approval of Gilenya to treat multiple sclerosis in pediatric patients. May 11, 2018. Available at: Accessed July 28, 2019.
2 Chitnis, T, Arnold DL, Banwell B, et al. Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med. 2018;379(11):1017-27.
3 Waubant E, Banwell B, Wassmer E, et al. Clinical trials of disease-modifying agents in pediatric MS. Neurology. May 2019, 92 (22) e2538-e2549; DOI:10.1212/WNL.0000000000007572.