Clinical trial NCT02200770: N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders
Official title: A Double-masked, Placebo-controlled Study With Open-label Period to Evaluate the Efficacy and Safety of MEDI-551 in Adult Subjects With Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders
Keywords: NMO, NMOSD, Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorders, autoimmune, demyelination, MEDI-551, monoclonal antibody, Devic's syndrome, B-cell
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-07-25
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Inebilizumab is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen cluster of differentiation (CD19) resulting in the depletion of B cells. Inebilizumab depletes antibody-secreting plasmablasts and some plasma cells, which are generally CD19 positive and CD20 negative.

The main objective of this study is to determine whether inebilizumab compare to placebo decreases the risk of an attack in participants with NMO/NMOSD.

This is a multicenter, multinational, randomized, double-masked, placebo controlled study with an open-label extension period to evaluate the efficacy and safety of intravenous (IV) inebilizumab in adult participants with NMO/NMOSD. After a screening period, eligible participants will enter a randomized-controlled period (RCP) of maximum 197 days where they will be randomized in a 3:1 ratio to receive either IV inebilizumab or placebo. NMO/NMOSD attacks will be evaluated by the investigator and confirmed against the attack criteria by an independent Adjudication Committee (AC). Participants for whom the attack was confirmed by the AC will be given the option to enroll into an open label period (OLP) with inebilizumab treatment. Participants who complete the RCP without experiencing an attack will be given the option to enroll into an OLP with inebilizumab treatment. The OLP will continue for a minimum of 1 year and a maximum of 3 years after the last participant enter the OLP. All participants who discontinue from the RCP or the OLP will continue in a Safety Follow-up for a total of 12 months from last dose to evaluate the long-term safety of the investigational product.

Eligibility criteria: Inclusion Criteria:

1. Men and women 18 years or older with diagnosis of NMO/NMOSD
2. Confirmation of NMO/NMOSD status:

   1. 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
   2. 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
3. Able and willing to give written informed consent and comply with the requirements of the study protocol.
4. EDSS \<= 7.5 (8 in special circumstances)
5. 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.

Exclusion Criteria:

1. Lactating and pregnant females
2. Treatment with any investigational agent within 4 weeks of screening
3. Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy.
4. Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization.
5. History of alcohol, drug, or chemical abuse, or a recent history of such abuse \< 1 year prior to randomization
6. Receipt of the following at any time prior to randomization:

   1. Alemtuzumab
   2. Total lymphoid irradiation
   3. Bone marrow transplant
   4. T-cell vaccination therapy
7. Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
8. Receipt of intravenous immunoglobulin (IVIG) within 1 month prior to randomization.
9. Receipt of any of the following within 3 months prior to randomization:

   1. Natalizumab (Tysabri®).
   2. Cyclosporin
   3. Methotrexate
   4. Mitoxantrone
   5. Cyclophosphamide
   6. Tocilizumab
   7. Eculizumab
10. History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)
11. Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection
12. History of malignancies, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy \> 3 months prior to randomization
13. Any concomitant disease other than NMO/NMOSD that required treatment with oral or intravenous steroids at doses over 20 mg a day for over 21 days

Primary outcomes:
measure: Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP
timeFrame: Day 1 (Baseline) through Day 197
Secondary outcomes:
measure: Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP
timeFrame: Day 1 (Baseline) through Day 197
measure: Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP
timeFrame: Day 1 (Baseline) through Day 197
measure: Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP
timeFrame: From Screening (Day -28) to Day 197
measure: Number of NMOSD-related In-patient Hospitalizations During RCP
timeFrame: Day 1 (Baseline) through Day 197
measure: Annualized AC-determined NMOSD Attack Rate During Any Exposure to Inebilizumab
timeFrame: 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)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP
timeFrame: Day 1 (Baseline) through Day 197
measure: Number of Participants With TEAEs and TESAEs During OLP
timeFrame: Day 198 through end of OLP period (maximum of 3 years after the last participant entered, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
measure: Number of Participants With TEAEs and TESAEs During SFP (Open-label Population)
timeFrame: Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)
measure: Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population)
timeFrame: Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)
measure: Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP
timeFrame: Day 1 (Baseline) through Day 197
measure: Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP
timeFrame: Day 198 through end of OLP (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
measure: Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP)
timeFrame: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
measure: Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP)
timeFrame: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
measure: Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP)
timeFrame: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP)
timeFrame: Pre and post dose on Day 1; and on Days 29, 85, and 197
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP)
timeFrame: Pre and post dose on Day 1; and on Days 92, 183, 274, and then every 6 months (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Sacramento
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Maitland
country: United States
facility: Research Site
state: Florida
city: Chicago
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facility: Research Site
state: Illinois
city: Kansas City
country: United States
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state: Kansas
city: Baltimore
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state: Maryland
city: Detroit
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state: Michigan
city: Rochester
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state: Minnesota
city: Saint Louis
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state: Missouri
city: Raleigh
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state: North Carolina
city: Cincinnati
country: United States
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state: Ohio
city: Cleveland
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state: Ohio
city: Mansfield
country: United States
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state: Ohio
city: Dallas
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Richmond
country: United States
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state: Virginia
city: Melbourne
country: Australia
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Barranquilla
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Cali
country: Colombia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Teplice
country: Czechia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Düsseldorf
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Muenster
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: HongKong
country: Hong Kong
facility: Research Site
city: Esztergom
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Aomori-shi
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Ota-ku
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Tsukuba
country: Japan
facility: Research Site
city: Goyang
country: Korea, Republic of
facility: Research Site
city: Jongno-gu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Ciudad De Mexico
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: San Luis Potosi
country: Mexico
facility: Research Site
city: Chisinau
country: Moldova, Republic of
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Bellavista
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Lódz
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Belgorod
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Khabarovsk
country: Russian Federation
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Changhua City
country: Taiwan
facility: Research Site
city: Hualien City
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune, LLC MedImmune, LLC
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.