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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

Tracking Information
First Submitted Date  ICMJE July 16, 2014
First Posted Date  ICMJE July 25, 2014
Last Update Posted Date June 12, 2019
Actual Study Start Date  ICMJE January 6, 2015
Actual Primary Completion Date October 26, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02200770 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2017)
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
  • 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
  • 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.
  • 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.
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Double-masked, Placebo-controlled Study With Open Label Period to Evaluate MEDI-551 in Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders
Intervention  ICMJE
  • Biological: MEDI-551
  • Other: Placebo
    Matching placebo
Study Arms  ICMJE
  • Experimental: MEDI551
    Intervention: Biological: MEDI-551
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 12, 2018)
231
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2014)
320
Estimated Study Completion Date  ICMJE October 21, 2022
Actual Primary Completion Date October 26, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   Colombia,   Czechia,   Estonia,   Germany,   Greece,   Hong Kong,   Hungary,   Israel,   Japan,   Korea, Republic of,   Mexico,   Moldova, Republic of,   New Zealand,   Peru,   Poland,   Russian Federation,   Serbia,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   United States
Removed Location Countries China,   Czech Republic,   India,   Netherlands,   Portugal,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT02200770
Other Study ID Numbers  ICMJE CD-IA-MEDI-551-1155
2014-000253-36 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MedImmune LLC
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP