title: Placebo-controlled study in neuromyelitis optica-Ethical and design considerations.
abstract: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported.
  
  
  
  To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA bruce.cree@ucsf.edu.
authors.forename: Bruce Ac
authors.initials: BA
authors.lastname: Cree
authors.affiliation: Program in Neuroscience, Departments of Neurology and Ophthalmology, University of Colorado, Denver, CO, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bennett
authors.affiliation: The Ethox Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Sheehan
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Berlin, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Berlin, Germany.
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.affiliation: Research Institute and Hospital of National Cancer Center, Goyang, South Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Charite-University Medicine Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Pittock
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Weinshenker
authors.affiliation: Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Wingerchuk
authors.affiliation: Tohoku University, Sendai, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.affiliation: The University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Cutter
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Patra
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Flor
authors.affiliation: MedImmune, Cambridge, UK.
authors.forename: Gerard
authors.initials: G
authors.lastname: Barron
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Soraya
authors.initials: S
authors.lastname: Madani
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Ratchford
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Katz
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D032984:Ethics, Research; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; C000609745:inebilizumab
keywords: MEDI-551; Neuromyelitis optica; anti-CD19 monoclonal antibody; ethics; trial design