NCT02200770

Brief Summary

To compare the efficacy of inebilizumab (MEDI-551) versus placebo in reducing the risk of an neuromyelitis optica/neuromyelitis optica- spectrum disorders (NMO/NMOSD) attack in participants with NMO/NMOSD.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
231

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2015

Longer than P75 for phase_2

Geographic Reach
24 countries

96 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 16, 2014

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 25, 2014

Completed
8 months until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 26, 2018

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

December 26, 2019

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 6, 2020

Completed
Last Updated

December 3, 2021

Status Verified

November 1, 2021

Enrollment Period

3.6 years

First QC Date

July 16, 2014

Results QC Date

October 24, 2019

Last Update Submit

November 3, 2021

Conditions

Keywords

NMO, NMOSD, Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorders, autoimmune, demyelination, MEDI-551, monoclonal antibody, Devic's syndrome, B-cell

Outcome Measures

Primary Outcomes (1)

  • Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP

    The NMOSD attack is defined as the presence of new or worsening symptom(s) related to NMOSD that meet at least one of the 18 protocol-defined attack criteria. These criteria were developed in conjunction with a panel of disease experts and with Food and Drug Administration input, and were intended to be clinically meaningful, objective, quantifiable, and able to be used worldwide. Only attacks positively adjudicated by the AC were used for the primary analysis.

    Day 1 (Baseline) through Day 197

Secondary Outcomes (16)

  • Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP

    Day 1 (Baseline) through Day 197

  • Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP

    Day 1 (Baseline) through Day 197

  • Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP

    From Screening (Day -28) to Day 197

  • Number of NMOSD-related In-patient Hospitalizations During RCP

    Day 1 (Baseline) through Day 197

  • Annualized AC-determined NMOSD Attack Rate During Any Exposure to Inebilizumab

    For participants randomized to inebilizumab: Day 1 of RCP through end of OLP (approximately 3.5 years); and for participants randomized to placebo: Day 1 of OLP through the end of OLP (approximately 3 years)

  • +11 more secondary outcomes

Study Arms (2)

Placebo/Inebilizumab

PLACEBO COMPARATOR

Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants will receive IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who enter OLP will receive IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants will have choice to enter in the SFP at any point during RCP or OLP and will be free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants will continue in the SFP for 12 months from last dose of study drug.

Drug: InebilizumabOther: Placebo

Inebilizumab/Inebilizumab

EXPERIMENTAL

AQP4-IgG sero positive and sero negative participants will IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who enter OLP will receive IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants will have choice to enter in the SFP at any point during RCP or OLP and will be free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants will continue in the SFP for 12 months from last dose of study drug.

Drug: InebilizumabOther: Placebo

Interventions

Participants will receive IV inebilizumab 300 mg.

Also known as: MEDI-551
Inebilizumab/InebilizumabPlacebo/Inebilizumab
PlaceboOTHER

Participants will receive IV placebo matched to inebilizumab.

Inebilizumab/InebilizumabPlacebo/Inebilizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men and women 18 years or older with diagnosis of NMO/NMOSD
  • Confirmation of NMO/NMOSD status:
  • AQP4-IgG sero-positive NMO/NMOSD with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years
  • AQP4-IgG sero-negative NMO with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years
  • Able and willing to give written informed consent and comply with the requirements of the study protocol.
  • EDSS \<= 7.5 (8 in special circumstances)
  • Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product.

You may not qualify if:

  • Lactating and pregnant females
  • Treatment with any investigational agent within 4 weeks of screening
  • Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy.
  • Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization.
  • History of alcohol, drug, or chemical abuse, or a recent history of such abuse \< 1 year prior to randomization
  • Receipt of the following at any time prior to randomization:
  • Alemtuzumab
  • Total lymphoid irradiation
  • Bone marrow transplant
  • T-cell vaccination therapy
  • Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
  • Receipt of intravenous immunoglobulin (IVIG) within 1 month prior to randomization.
  • Receipt of any of the following within 3 months prior to randomization:
  • Natalizumab (Tysabri®).
  • Cyclosporin
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (98)

Research Site

Birmingham, Alabama, 35294, United States

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Sacramento, California, 95817, United States

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San Francisco, California, 94158, United States

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Aurora, Colorado, 80010, United States

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New Haven, Connecticut, 06511, United States

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Maitland, Florida, 32751, United States

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Chicago, Illinois, 60637, United States

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Kansas City, Kansas, 66160, United States

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Baltimore, Maryland, 21287, United States

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Detroit, Michigan, 48201, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63131-2374, United States

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Raleigh, North Carolina, 27607, United States

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Cincinnati, Ohio, 45219, United States

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Cleveland, Ohio, 44195, United States

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Mansfield, Ohio, 44906, United States

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Dallas, Texas, 75390, United States

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Houston, Texas, 77030, United States

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Richmond, Virginia, 23298, United States

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Melbourne, 3065, Australia

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Sofia, 1113, Bulgaria

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Sofia, 1309, Bulgaria

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Sofia, 1431, Bulgaria

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Varna, 9010, Bulgaria

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Vancouver, British Columbia, V6T 2B5, Canada

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Barranquilla, 080020, Colombia

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Bogotá, 110131, Colombia

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Bogotá, 110231, Colombia

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Cali, 760032, Colombia

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Olomouc, 775 20, Czechia

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Prague, 121 11, Czechia

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Teplice, 415 29, Czechia

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Tallinn, 10617, Estonia

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Tartu, 51014, Estonia

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Berlin, 10117, Germany

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Dresden, 01307, Germany

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Düsseldorf, 40225, Germany

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Leipzig, 04103, Germany

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Münster, 48149, Germany

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Rostock, 18147, Germany

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Hong Kong, Hong Kong

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Esztergom, 2500, Hungary

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Nyíregyháza, 4400, Hungary

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Szeged, 6725, Hungary

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Jerusalem, 91120, Israel

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Ramat Gan, 52621, Israel

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Tel Aviv, 6423906, Israel

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Aomori, 030-8553, Japan

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Bunkyō City, 113-8431, Japan

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Kyoto, 604-8453, Japan

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Ōta-ku, 145-0065, Japan

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Sendai, 980-8574, Japan

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Tsukuba, 305-8577, Japan

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Mexico City, 03310, Mexico

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Mexico City, 14269, Mexico

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Monterrey, 64460, Mexico

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San Luis Potosí City, 78090, Mexico

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Chisinau, 2028, Moldova

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Auckland, 1023, New Zealand

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Bellavista, CALLAO 2, Peru

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Lima, LIMA 01, Peru

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Katowice, 40-595, Poland

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Krakow, 31-637, Poland

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Lódz, 90-324, Poland

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Lublin, 20-954, Poland

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Olsztyn, 10-560, Poland

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Warsaw, 02-097, Poland

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Warsaw, 02-957, Poland

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Belgorod, 308007, Russia

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Kazan', 420021, Russia

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Khabarovsk, 680009, Russia

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Krasnoyarsk, 660037, Russia

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Moscow, 123367, Russia

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Moscow, 127018, Russia

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Nizhny Novgorod, 603155, Russia

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Novosibirsk, 63007, Russia

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Omsk, 644033, Russia

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Saint Petersburg, 197110, Russia

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Ufa, 450005, Russia

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Belgrade, 11129, Serbia

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Cape Town, 7505, South Africa

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Cape Town, 7925, South Africa

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Goyang, 410-769, South Korea

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Jongno-gu, 110-744, South Korea

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Seoul, 135-710, South Korea

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Seoul, 143729, South Korea

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Madrid, 28040, Spain

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Changhua, 50006, Taiwan

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Hualien City, 97002, Taiwan

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Tainan, 70403, Taiwan

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Bangkok, 10700, Thailand

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Muang, 40002, Thailand

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Muang, 50200, Thailand

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Istanbul, 34098, Turkey (Türkiye)

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Istanbul, 34147, Turkey (Türkiye)

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Istanbul, 34890, Turkey (Türkiye)

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Izmir, 35170, Turkey (Türkiye)

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Samsun, 55139, Turkey (Türkiye)

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Related Publications (9)

  • Cree BAC, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, She D, Rees W, Smith M, Cimbora D, Katz E, Bennett JL; N-MOmentum study investigators. Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial. Lancet Neurol. 2024 Jun;23(6):588-602. doi: 10.1016/S1474-4422(24)00077-2.

  • Aktas O, Hartung HP, Smith MA, Rees WA, Fujihara K, Paul F, Marignier R, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Cutter G, She D, Gunsior M, Cimbora D, Katz E, Cree BA; N-MOmentum study investigators. Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder. J Neurol Neurosurg Psychiatry. 2023 Sep;94(9):757-768. doi: 10.1136/jnnp-2022-330412. Epub 2023 May 23.

  • Bennett JL, Aktas O, Rees WA, Smith MA, Gunsior M, Yan L, She D, Cimbora D, Pittock SJ, Weinshenker BG, Paul F, Marignier R, Wingerchuk D, Cutter G, Green A, Hartung HP, Kim HJ, Fujihara K, Levy M, Katz E, Cree BAC; N-MOmentum study investigators. Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial. EBioMedicine. 2022 Dec;86:104321. doi: 10.1016/j.ebiom.2022.104321. Epub 2022 Nov 10.

  • Flanagan EP, Levy M, Katz E, Cimbora D, Drappa J, Mealy MA, She D, Cree BAC. Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study. Mult Scler Relat Disord. 2022 Jan;57:103352. doi: 10.1016/j.msard.2021.103352. Epub 2021 Oct 26.

  • Marignier R, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk D, Fujihara K, Paul F, Cutter GR, Green AJ, Aktas O, Hartung HP, Lublin FD, Williams IM, Drappa J, She D, Cimbora D, Rees W, Smith M, Ratchford JN, Katz E, Cree BAC; N-MOmentum Study Investigators. Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder. Neurol Neuroimmunol Neuroinflamm. 2021 Mar 26;8(3):e978. doi: 10.1212/NXI.0000000000000978. Print 2021 May.

  • Aktas O, Smith MA, Rees WA, Bennett JL, She D, Katz E, Cree BAC; N-MOmentum scientific group and the N-MOmentum study investigators. Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker. Ann Neurol. 2021 May;89(5):895-910. doi: 10.1002/ana.26067. Epub 2021 Mar 30.

  • Cree BA, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk D, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, Williams IM, Drappa J, She D, Cimbora D, Rees W, Ratchford JN, Katz E. Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD. Mult Scler. 2021 Nov;27(13):2052-2061. doi: 10.1177/1352458521988926. Epub 2021 Feb 4.

  • Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, Lublin FD, Drappa J, Barron G, Madani S, Ratchford JN, She D, Cimbora D, Katz E; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019 Oct 12;394(10206):1352-1363. doi: 10.1016/S0140-6736(19)31817-3. Epub 2019 Sep 5.

  • Cree BA, Bennett JL, Sheehan M, Cohen J, Hartung HP, Aktas O, Kim HJ, Paul F, Pittock S, Weinshenker B, Wingerchuk D, Fujihara K, Cutter G, Patra K, Flor A, Barron G, Madani S, Ratchford JN, Katz E. Placebo-controlled study in neuromyelitis optica-Ethical and design considerations. Mult Scler. 2016 Jun;22(7):862-72. doi: 10.1177/1352458515620934. Epub 2015 Dec 14.

Related Links

MeSH Terms

Conditions

Neuromyelitis OpticaDemyelinating Diseases

Interventions

inebilizumab

Condition Hierarchy (Ancestors)

Myelitis, TransverseDemyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesOptic NeuritisOptic Nerve DiseasesCranial Nerve DiseasesEye DiseasesAutoimmune DiseasesImmune System Diseases

Limitations and Caveats

In the safety follow-up period (SFP), only 1 participant from 'Placebo/Inebilizumab' arm rolled over to SFP and no participant from 'Inebilizumab /Inebilizumab' arm rolled over to SFP. For EudraCT result posting, a study period with any one of the arm with zero participants started is not acceptable (EudraCT limitation). Therefore, not included SFP in 'Participant Flow' section to keep the data consistent across registry portals.

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca Clinical study Information Center

Study Officials

  • MedImmune, LLC MedImmune, LLC

    MedImmune LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 16, 2014

First Posted

July 25, 2014

Study Start

April 1, 2015

Primary Completion

October 26, 2018

Study Completion

November 6, 2020

Last Updated

December 3, 2021

Results First Posted

December 26, 2019

Record last verified: 2021-11

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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