Placebo-controlled study in neuromyelitis optica—Ethical and design considerations. (June 2016)

• Record Type: Journal Article
• Authors: Cree, Bruce AC; Bennett, Jeffrey L; Sheehan, Mark; Cohen, Jeffrey; Hartung, Hans-Peter; Aktas, Orhan; Kim, Ho Jin; Paul, Friedemann; Pittock, Sean; Weinshenker, Brian; Wingerchuk, Dean; Fujihara, Kazuo; Cutter, Gary; Patra, Kaushik; Flor, Armando; Barron, Gerard; Madani, Soraya; Ratchford, John N; Katz, Eliezer
• Is Part Of: Multiple sclerosis. Volume 22:Number 7(2016)
• Page Start: 862
• Page End: 872
• Publication Date: 2016-06
• Subjects: Neuromyelitis optica -- trial design -- ethics -- MEDI-551 -- anti-CD19 monoclonal antibody; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458515620934
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported. Objective: To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical–scientific integrity. Methods: We assessed the "standard of care" for NMO to establish the ethical framework for a placebo-controlled trial. We implemented measures that balance the need for scientific robustness while mitigating the risks associated with a placebo-controlled study. The medical or scientific community, patient organizations, and regulatory authorities were engaged early in discussions on this placebo-controlled study, and their input contributed to the final study design. Results: The N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo. The study design has received regulatory, ethical, clinical, and patient approval in over 100 clinical sites in more than 20 countries worldwide. Conclusion: The approach we took in the design of the N-MOmentum trial might serve as a roadmap for other rare severe diseases when there is no proven therapy and no established clinical development path.