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A Double-masked, Placebo-controlled Study With Open Label Period to Evaluate MEDI-551 in Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders

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ClinicalTrials.gov Identifier: NCT02200770
Recruitment Status : Active, not recruiting
First Posted : July 25, 2014
Last Update Posted : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
To compare the efficacy of MEDI-551 versus placebo in reducing the risk of an NMO/NMOSD attack in subjects with NMO/NMOSD.

Condition or disease Intervention/treatment Phase
Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders Biological: MEDI-551 Other: Placebo Phase 2 Phase 3

Detailed Description:

MEDI-551 is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen CD19 resulting in the depletion of B cells. CD19 positive (CD19+) B-lineage plasmablasts are responsible for the production of autoantibodies against the AQP4 channel protein.

The main objective of this study is to determine whether MEDI-551 compare to placebo decreases the risk of an attack in subjects 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) MEDI-551 in adult subjects with NMO/NMOSD.

After a screening period, eligible subjects 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 MEDI-551 or placebo. NMO/NMOSD attacks will be evaluated by the investigator and confirmed against the attack criteria by an independent Adjudication Committee (AC). Subjects for whom the attack was confirmed by the AC will be given the option to enroll into an open label period (OLP) with MEDI-551 treatment. Subjects who complete the RCP without experiencing an attack will be given the option to enroll into an OLP with MEDI-551 treatment. The OLP will continue for a minimum of 1 year and a maximum of 3 years after the last subject enter the OLP.

All subjects 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 231 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 6, 2015
Actual Primary Completion Date : October 26, 2018
Estimated Study Completion Date : October 21, 2022


Arm Intervention/treatment
Experimental: MEDI551 Biological: MEDI-551
Placebo Comparator: Placebo Other: Placebo
Matching placebo




Primary Outcome Measures :
  1. Time to onset of an adjudicated NMO/NMOSD attack [ Time Frame: From Day 1 of the study until on or before Day 197 of the randomized-controlled period. ]
    time (days) to onset of an Adjudication Committee (AC) - determined NMO/NMOSD attack


Secondary Outcome Measures :
  1. Attack Rate [ Time Frame: Annualized attack rate normalized by person/years during the open-label period, for a minimum of 1 year after the last subject enters and a maximum of 3 years after the last subject enters ]
    Annualized attack rate (total number of adjudicated NMO/NMOSD attacks normalized by person-years) during the duration of the Open-label Period

  2. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From the start of treatment with investigational product until the end of the Safety Follow-up Period, for a total of 12 months following the last dose of investigational product ]
    Treatment-emergent adverse events, treatment-emergent serious adverse events (TESAEs), including laboratory measurements as well as their changes or shift from baseline over time

  3. TMAX and CMAX [ Time Frame: From Day 1 of the study until on or before Day 197 of the randomized-controlled period. ]
    mean MEDI-551 concentration versus time data will be plotted by AQP4-IgG seropositive and seronegative subjects

  4. Incidence of Anti-Drug Antibodies (ADAs) Directed Against MEDI-551 [ Time Frame: From the start of treatment with investigational product until the end of the Safety Follow-up Period, for a total of 12 months following the last dose of investigational product ]
    Incidence of anti-drug antibodies (ADAs) directed against MEDI-551 (both predose and postdose for each subject)

  5. Worsening in EDSS [ Time Frame: From the start of treatment with invesigational product up to Day 197 of Randomised Control Period ]
    Worsening from baseline in EDSS at last visit during the RCP

  6. Change in Low-Contrast Visual Acuity Binocular Score [ Time Frame: From the start of treatment with invesigational product up to Day 197 of Randomised Control Period ]
    Change from baseline in low-contrast visual acuity binocular score measured by low-contrast Landolt C Broken Rings Chart

  7. Cumulative Total Active MRI Lesions [ Time Frame: From the start of treatment with invesigational product up to Day 197 of Randomised Control Period ]
    Cumulative total active MRI lesions (new Gd-enhancing or new/enlarging T2)

  8. Number of NMO/NMOSD-Related In-Patient Hospitalizations [ Time Frame: From the start of treatment with invesigational product up to Day 197 of Randomised Control Period ]
    Number of NMO/NMOSD-related in-patient hospitalizations



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 IVIG within 1 month prior to randomization.
  9. Receipt of any of the following within 3 months prior to randomization:

    1. Natalizumab (Tysabri®)b.
    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02200770


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Locations
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United States, Alabama
Research Site
Birmingham, Alabama, United States, 35294
United States, California
Research Site
Sacramento, California, United States, 95817
Research Site
San Francisco, California, United States, 94158
United States, Colorado
Research Site
Aurora, Colorado, United States, 80010
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06511
United States, Florida
Research Site
Maitland, Florida, United States, 32751
Research Site
Tampa, Florida, United States, 33612
United States, Illinois
Research Site
Chicago, Illinois, United States, 60637
United States, Kansas
Research Site
Kansas City, Kansas, United States, 66160
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21287
United States, Michigan
Research Site
Detroit, Michigan, United States, 48201
United States, Minnesota
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Rochester, Minnesota, United States, 55905
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63131-2374
United States, New York
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Buffalo, New York, United States, 14203
United States, North Carolina
Research Site
Raleigh, North Carolina, United States, 27607
United States, Ohio
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Cincinnati, Ohio, United States, 45219
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Cleveland, Ohio, United States, 44195
Research Site
Mansfield, Ohio, United States, 44906
United States, Pennsylvania
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Philadelphia, Pennsylvania, United States, 19106
United States, Texas
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Dallas, Texas, United States, 75390
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Houston, Texas, United States, 77030
United States, Virginia
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Richmond, Virginia, United States, 23298
Australia
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Melbourne, Australia, 3065
Bulgaria
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Sofia, Bulgaria, 1113
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Sofia, Bulgaria, 1309
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Sofia, Bulgaria, 1431
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Varna, Bulgaria, 9010
Canada, British Columbia
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Vancouver, British Columbia, Canada, V6T 2B5
Colombia
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Barranquilla, Colombia, 080020
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Bogota, Colombia, 110131
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Bogota, Colombia, 110231
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Cali, Colombia, 760032
Czechia
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Olomouc, Czechia, 775 20
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Praha 2, Czechia, 121 11
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Teplice, Czechia, 415 29
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Tallinn, Estonia, 10617
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Tartu, Estonia, 51014
Germany
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Berlin, Germany, 10117
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Dresden, Germany, 01307
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Düsseldorf, Germany, 40225
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Leipzig, Germany, 04103
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Marburg, Germany, 35043
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Munster, Germany, 48149
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Rostock, Germany, 18147
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Tuebingen, Germany, 72076
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Athens, Greece, 11525
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Athens, Greece, 11528
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Hong Kong, Hong Kong
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HongKong, Hong Kong
Hungary
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Budapest, Hungary, 1033
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Esztergom, Hungary, 2500
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Nyiregyhaza, Hungary, 4400
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Szeged, Hungary, 6725
Israel
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Jerusalem, Israel, 91120
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Ramat Gan, Israel, 52621
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Tel Aviv, Israel, 6423906
Japan
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Aomori-shi, Japan, 030-8553
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Bunkyo-ku, Japan, 113-8431
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Kyoto-shi, Japan, 604-8453
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Ota-ku, Japan, 145-0065
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Sendai-shi, Japan, 980-8574
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Tsukuba, Japan, 305-8577
Korea, Republic of
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Goyang, Korea, Republic of, 410-769
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Jongno-gu, Korea, Republic of, 110-744
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Seoul, Korea, Republic of, 135-710
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Seoul, Korea, Republic of, 143729
Mexico
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Ciudad De Mexico, Mexico, 14269
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Mexico City, Mexico, 03310
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Monterrey, Mexico, 64460
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San Luis Potosi, Mexico, 78090
Moldova, Republic of
Research Site
Chisinau, Moldova, Republic of, 2028
New Zealand
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Auckland, New Zealand, 1023
Peru
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Bellavista, Peru, CALLAO 2
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Lima, Peru, LIMA 01
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Lima, Peru, Lima 11
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Lima, Peru, LIMA 31
Poland
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Katowice, Poland, 40-595
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Krakow, Poland, 31-637
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Lublin, Poland, 20-954
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Lódz, Poland, 90-324
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Olsztyn, Poland, 10-560
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Warszawa, Poland, 02-097
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Warszawa, Poland, 02-957
Russian Federation
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Belgorod, Russian Federation, 308007
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Kazan, Russian Federation, 420021
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Khabarovsk, Russian Federation, 680009
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Kirov, Russian Federation, 610007
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Krasnoyarsk, Russian Federation, 660037
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Moscow, Russian Federation, 115516
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Moscow, Russian Federation, 123367
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Moscow, Russian Federation, 127018
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Nizhniy Novgorod, Russian Federation, 603155
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Novosibirsk, Russian Federation, 63007
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Omsk, Russian Federation, 644033
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Saint-Petersburg, Russian Federation, 197110
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Ufa, Russian Federation, 450005
Serbia
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Belgrade, Serbia, 11129
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Nis, Serbia, 18000
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Uzice, Serbia, 31000
South Africa
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Cape Town, South Africa, 7505
Research Site
Cape Town, South Africa, 7925
Spain
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Madrid, Spain, 28040
Taiwan
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Changhua City, Taiwan, 50006
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Hualien City, Taiwan, 970
Research Site
Tainan, Taiwan, 70403
Thailand
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Bangkok, Thailand, 10700
Research Site
Khlong Luang, Thailand, 12120
Research Site
Muang, Thailand, 40002
Research Site
Muang, Thailand, 50200
Turkey
Research Site
Istanbul, Turkey, 34098
Research Site
Istanbul, Turkey, 34147
Research Site
Istanbul, Turkey, 34890
Research Site
Izmir, Turkey, 35170
Research Site
Samsun, Turkey, 55139
Sponsors and Collaborators
MedImmune LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02200770     History of Changes
Other Study ID Numbers: CD-IA-MEDI-551-1155
2014-000253-36 ( EudraCT Number )
First Posted: July 25, 2014    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MedImmune LLC:
NMO, NMOSD, Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorders, autoimmune, demyelination, MEDI-551, monoclonal antibody, Devic's syndrome, B-cell

Additional relevant MeSH terms:
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Disease
Neuromyelitis Optica
Pathologic Processes
Myelitis, Transverse
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases