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Global Agreement on Standards for Clinical Trials Involving Children and Adolescents with MS

May 21, 2019

  • The International Pediatric MS Study Group -- a group of care providers and researchers looking to optimize worldwide care, education and research in pediatric MS -- was convened in January 2018 with sponsorship by the National MS Society (USA) and the MS Society of Canada.
  • Stemming from this meeting and subsequent review by members, the group has updated its recommendations on conducting clinical trials in children and adolescents with MS.
  • The team (Emmanuelle Waubant, MD, PhD, University of California, San Francisco, and colleagues) report these updated recommendations in Neurology (published online May 1, 2019).  
DETAILS
Background: Although MS occurs most commonly in adults, it is also less frequently diagnosed in children and adolescents. Most clinical trials of new therapies for MS are tested only in adults. However, in 2018 the U.S. Food and Drug Administration approved the expansion of the use of the oral MS therapy Gilenya® (fingolimod, Novartis AG) to include the treatment of children and adolescents 10 years of age or older with relapsing MS, based on a controlled clinical trial in pediatric MS. Other oral therapies for MS, including dimethyl fumarate (Tecfidera®, Biogen) and teriflunomide (Aubagio®, Genzyme, a Sanofi company), are currently under study in clinical trials for the treatment of pediatric MS. 
 
Conducting clinical trials in children can be complicated; some issues include the low numbers of children with MS at any one study site, the necessity to obtain parental approval in addition to the child agreeing to participate, and the fact that treatments can have unanticipated side effects in immature individuals. The International Pediatric Multiple Sclerosis Study Group (IPMSSG) is a group of 165 care providers representing 44 countries, dedicated to optimizing worldwide care, education and research in pediatric MS. In 2012, they held an international meeting to develop consensus on how to conduct clinical trials in children with MS. (Neurology. 2013 Mar 19;80(12):1161-8) In 2018, they recognized the need to update this consensus, and convened a meeting in New York City in January, which was sponsored by the National MS Society (USA) and the MS Society of Canada.
                                                                                                                                                                                
The Meeting:
At the meeting, the group reviewed progress and identified issues and recommendations to implement in future trials of experimental treatments for children/adolescents with MS, and also areas that require more discussion. After the meeting, other members were consulted to develop a consensus on recommendations, including the following:
  • Pharmacokinetic/pharmacodynamic studies (how a therapy is absorbed and how it affects the patient) should be completed for all new agents to identify the appropriate dose in children.
  • If an immune-modulating agent has been proven to be effective in adult MS, it is inappropriate to test that agent in pediatric MS using a placebo (inactive) control.
  • In some cases, when therapies have been well studied in adults, an open-label study (including pharmacokinetic/pharmacodynamic and safety endpoints) should be considered as sufficient for approval in pediatric MS.
  • No more than one phase 3 clinical trial should be performed for an experimental treatment in children/adolescents with MS.
  • Phase 3 trials in adults should consider enrolling teenagers.
  • Controlled trials of immune-modulating agents can use fingolimod as a control, or other treatments commonly used in pediatric MS.
  • It’s preferable to use a primary endpoint that involves disease activity on MRI scans. If a regulatory agency mandates a clinical endpoint, it’s better to use “time to relapse” rather than relapse rate, because this endpoint would allow for a quicker switch to more effective therapies if necessary.
  • Open-label studies (that do not require a comparison) or registries should be designed to monitor treatment safety in children 12 or under.
  • Open-label extension studies should be mandated for trials in pediatric MS.  
The team (Emmanuelle Waubant, MD, PhD, University of California, San Francisco, and colleagues) report these  updated recommendations in Neurology (published online May 1, 2019).
 
Next Steps: The group pointed to critical areas that should be addressed by future research, including exploring the effectiveness of doing office visits via teleconference; refining the criteria that children need to meet to be included in a clinical trial; and determining the role of novel ways to measure treatment effectiveness, such as optical coherence tomography, which can measure nerve damage less invasively in the eye.
 
Read More
Learn more about Pediatric MS
 
Gilenya is a registered trademark of Novartis AG
Tecfidera is a registered trademark of Biogen
Aubagio is a registered trademark of Sanofi Genzyme
 

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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