International Pediatric MS Study Group Clinical Trials Summit Meeting report

Department of Neurology (M.P.A.), University of Florence, Florence, Italy
Neurology (Impact Factor: 8.29). 03/2013; 80(12):1161-1168. DOI: 10.1212/WNL.0b013e318288694e
Source: PubMed


Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research.

The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion. A total of 69 meeting attendees were assembled, including 35 academic experts. Regulatory and pharmaceutical representatives also attended, and provided input, which informed academic expert consensus decisions.

The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic, safety and efficacy data, and regulatory approval allowing for greater medication access. The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials. An international standardized cognitive battery was identified. The pros and cons of various trial designs were discussed. Guidelines surrounding MRI studies, pharmacokinetics, pharmacodynamics, and registries were developed. The academic experts agreed that given the limited subject pool, a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion. Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge.

Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts, informed by regulatory and industry stakeholders.

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Available from: Tanuja Chitnis, Sep 11, 2015
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    • "Lesion load measured early in the disease course is associated with future relapses [23, 33], disability accumulation [34, 35], and cognitive deficits [36]. Based on a meta-analysis of 23 clinical trials in relapsing-remitting MS, the association between the treatment effect on relapse rate is strongly correlated (R2 = 0.81) with the treatment effect on MRI lesions (i.e., new or active T2 lesions or gadolinium enhancing lesions if monthly scans were acquired) [37]. "
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    ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease that manifests as acute relapses and progressive disability. As a primary endpoint for clinical trials in MS, disability is difficult to both characterize and measure. Furthermore, the recovery from relapses and the rate of disability vary considerably among patients. Given these challenges, investigators have developed and studied the performance of various outcome measures and surrogate endpoints in MS clinical trials. This review defines the outcome measures and surrogate endpoints used to date in MS clinical trials and presents challenges in the design of both adult and pediatric trials.
    05/2014; 2014:262350. DOI:10.1155/2014/262350
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    • "A meeting report on Clinical Trial Summit from the Steering Committee of the International Pediatric MS Study Group (IPMSSG) has been recently published [91]. The academic leaders established guidelines for outcome measures, including clinical, cognitive, and MRI, to be considered in the pediatric MS clinical drug trials. "
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    ABSTRACT: Multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central nervous system (CNS) commonly diagnosed in adults, is being recognized increasingly in children. An estimated 1.7%-5.6% of all patients with MS have clinical symptoms before reaching the age of 18 years. In comparison with adults, the diagnosis of MS in children can be more difficult, being dismissed or misdiagnosed as other clinical disorders. Although adults and children share basic aspects of the disorder, children have distinctive clinical features, neuroimaging, laboratory, and courses of the disease. The 2010 McDonald criteria have simplified the requirements for establishing the diagnosis of MS and have been proposed to be applicable for the diagnosis of pediatric MS, mainly in children 12 years and older. This paper describes the distinctive features of common pediatric demyelinating disorders, including MS, and summarizes the most recent advances based on the available literature.
    11/2013; 2013(3):673947. DOI:10.1155/2013/673947
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    ABSTRACT: Objective To compare relapse rates in pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (AOMS) over the first 6-years of disease. Methods Patients with relapsing-remitting disease onset were identified from the Partners Pediatric MS Center, Massachusetts General Hospital and Partners MS Center, Brigham and Women's Hospital. 84 POMS and 258 AOMS patients were included. Annualized relapse rates (ARR) for each individual year from year 1 to year 6, after first attack were compared using Poisson regression, as was expanded disability status scale (EDSS) score at the visit closest to each year interval. Results ARR was significantly higher in POMS compared to AOMS at individual years (except year 4), and was not significantly affected by adjustment for gender, race and proportion of time on treatment. Despite a 2.30 times higher relapse rate over 6-years, EDSS between groups did not differ. ARR in years 1–5 did not impact year 5 disability measured by EDSS in POMS. Conclusions Our findings demonstrate that higher ARR in POMS relative to AOMS is sustained over 6-years, suggesting a more inflammatory nature and potential disconnect between relapses and disability measured by EDSS early in POMS. This data may be useful when designing clinical trials for POMS.
    Multiple Sclerosis and Related Disorders 01/2013; 3(2). DOI:10.1016/j.msard.2013.06.004 · 0.88 Impact Factor
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