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Efficacy and Safety Study of Satralizumab (SA237) as Monotherapy to Treat Participants With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)

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ClinicalTrials.gov Identifier: NCT02073279
Recruitment Status : Active, not recruiting
First Posted : February 27, 2014
Last Update Posted : June 7, 2019
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
The objectives of this study are to evaluate the efficacy, safety, pharmacodynamic, pharmacokinetic and immunogenic profiles of satralizumab in participants with NMO and NMOSD.

Condition or disease Intervention/treatment Phase
Neuromyelitis Optica (NMO) NMO Spectrum Disorder (NMOSD) Drug: Satralizumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) as Monotherapy in Patients With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)
Actual Study Start Date : August 5, 2014
Actual Primary Completion Date : October 12, 2018
Estimated Study Completion Date : March 31, 2021


Arm Intervention/treatment
Experimental: Satralizumab
Participants randomized to this arm for the double-blind period will receive satralizumab monotherapy. The double-blind period for the participant ends either when the participant experiences a Clinical Endpoint Committee (CEC) confirmed protocol-defined relapse, the total number of CEC confirmed protocol-defined relapses reaches 44, or 1.5 years after the last patient was randomized. In the open-label extension period, the participant will receive satralizumab SC injection at Weeks 0, 2, and 4, and Q4W thereafter, until commercial availability of satralizumab, the availability of satralizumab as post-trial access in accordance with local regulation, or Sponsor's decision of discontinuation of the development program.
Drug: Satralizumab
Satralizumab will be administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).
Other Names:
  • SA237
  • RG6168

Placebo Comparator: Placebo
Participants randomized to this arm for the double-blind period will receive placebo monotherapy. The double-blind period for the participant ends either when the participant experiences a Clinical Endpoint Committee (CEC) confirmed protocol-defined relapse, the total number of CEC confirmed protocol-defined relapses reaches 44, or 1.5 years after the last patient was randomized.. In the open-label extension period, the participant will receive satralizumab SC injection at Weeks 0, 2, and 4, and Q4W thereafter, until commercial availability of satralizumab, the availability of satralizumab as post-trial access in accordance with local regulation, or Sponsor's decision of discontinuation of the development program.
Drug: Satralizumab
Satralizumab will be administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).
Other Names:
  • SA237
  • RG6168

Drug: Placebo
Placebo will be administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).




Primary Outcome Measures :
  1. Time to First Protocol-Defined Relapse in the Double-Blind Period [ Time Frame: From the date of randomization until the first occurrence of relapse throughout the double-blind period (up to approximately 38 months) ]

Secondary Outcome Measures :
  1. Change from Baseline to Week 24 in the Visual Analogue Scale (VAS) Score for Pain [ Time Frame: Baseline, Week 24 ]
    The VAS for pain is a subjective measure and it consists of a 100 millimeter (mm) line with two end points representing 'no pain' to 'pain as bad as it could be'. Participants are asked to rate their pain by placing a mark on the line corresponding to their current level of pain. The distance along the line from the 'no pain' marker is then measured with a ruler giving a pain score out of 10.

  2. Change from Baseline to Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score [ Time Frame: Baseline, Week 24 ]
    FACIT fatigue scale includes 13 statements, which measures fatigue/asthenia for participants with chronic, life-threatening illnesses. For each question, a participant rates his/her condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). A score is calculated by averaging the individual question scores, with lower scores indicative of less fatigue.

  3. Change from Baseline Over Time in the Short Form Generic Health Survey (SF-36) Bodily Pain Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  4. Change from Baseline Over Time in the SF-36 General Health Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  5. Change from Baseline Over Time in the SF-36 Mental Health Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  6. Change from Baseline Over Time in the SF-36 Physical Functioning Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  7. Change from Baseline Over Time in the SF-36 Role-Emotional Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  8. Change from Baseline Over Time in the SF-36 Role-Physical Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  9. Change from Baseline Over Time in the SF-36 Social Role Functioning Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  10. Change from Baseline Over Time in the SF-36 Vitality Domain Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  11. Change from Baseline Over Time in the SF-36 Mental Component Summary Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  12. Change from Baseline Over Time in the SF-36 Physical Component Summary Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.

  13. Change from Baseline Over Time in the EuroQoL-5 Dimensions (EQ-5D) Index Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The EQ-5D is a participant-answered questionnaire measuring 5 dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with 3 possible response categories: 1) no problems; 2) some problems; 3) severe problems. The EQ-5D index score is scored on a scale of -0.2 to 1. A higher score reflects a better health state.

  14. Change from Baseline Over Time in the Timed 25-Foot Walk (T25W) [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The T25W is the measurement to assess walking ability. The time (in seconds) that it takes the participant to walk 25 feet is measured.

  15. Percentage of Participants Who Are Relapse-Free Over Time [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  16. Annualized Relapse Rate [ Time Frame: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  17. Change from Baseline Over Time in Modified Rankin Scale (mRS) Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The mRS is a 7-point disability scale that assesses the degree of disability in patients with neurological impairment. Possible scores range from 0 (no symptoms at all) up to 6 (death). Higher scores reflect increased disability.

  18. Change from Baseline Over Time in Zarit Burden Interview (ZBI) Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The ZBI is the measurement to assess caregiver burden. The 22 items ask for the strain caregivers perceive. Responses range from 0 (never) to 4 (nearly always). The overall ZBI score ranges from 0 to 88. The higher the total score, the heavier the perceived burden.

  19. Change from Baseline Over Time in Expanded Disability Status Scale (EDSS) Score [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
    The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.

  20. Change from Baseline Over Time in Visual Acuity (Snellen Chart) [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  21. Change from Baseline Over Time in Low-Contrast Visual Acuity, as Assessed Using the Low-Contrast Sloan Letter Chart (LCSLC) [ Time Frame: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  22. Number of Participants with at Least One Adverse Event by Severity [ Time Frame: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  23. Number of Participants with at Least One Serious Adverse Event by Severity [ Time Frame: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  24. Number of Participants with Non-Serious Adverse Events of Special Interest by Severity [ Time Frame: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  25. Number of Participants with Selected Adverse Events by Severity [ Time Frame: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 6.75 years) ]
  26. Number of Participants by Columbia-Suicide Severity Rating Scale (C-SSRS) Scores [ Time Frame: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks and every 12 weeks thereafter of open-label extension period (up to approximately 6.75 years) ]
  27. Serum Satralizumab Concentration Over Time [ Time Frame: Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks and every 24 weeks thereafter of open-label extension period (up to approximately 6.75 years) ]
  28. Serum Interleukin-6 (IL-6) Concentration Over Time [ Time Frame: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks of open-label extension period (up to approximately 6.75 years) ]
  29. Serum Soluble IL-6 Receptor (sIL-6R) Concentration Over Time [ Time Frame: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks of open-label extension period (up to approximately 6.75 years) ]
  30. Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration Over Time [ Time Frame: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks of open-label extension period (up to approximately 6.75 years) ]
  31. Blood Anti-Aquaporin-4 (AQP4) Antibody Concentration Over Time [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 24, 48, and every 24 weeks thereafter of double-blind period; every 24 weeks for first 48 weeks of open-label extension period (up to approximately 6.75 years) ]
  32. Blood Plasmablast Concentration Over Time [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 24, 48, and every 24 weeks thereafter of double-blind period (up to approximately 38 months) ]
  33. Number of Participants with Anti-Drug Antibodies to Satralizumab [ Time Frame: Baseline and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks and every 24 weeks thereafter of open-label extension period (up to approximately 6.75 years) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be diagnosed as having either neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD), defined as the following:

    1. NMO as defined by Wingerchuk et al. 2006 criteria (requires all of the following 3 criteria: I. Optic neuritis, II. Acute myelitis, III. At least two of three supportive criteria: Contiguous spinal cord lesion identified on a magnetic resonance imaging [MRI] scan extending over 3 vertebral segments; Brain MRI not meeting diagnostic criteria for multiple sclerosis [MS]; NMO-IgG seropositive status)
    2. NMOSD as defined by either of following criteria with anti-aquaporin-4 (AQP4) antibody seropositive status at screening: i. Idiopathic single or recurrent events of longitudinally extensive myelitis (≥3 vertebral segment spinal cord MRI lesion); ii. Optic neuritis, single, recurrent or simultaneous bilateral
  2. Clinical evidence of at least 1 documented relapse (including first attack) in last 12 months prior to screening
  3. Expanded Disability Status Scale (EDSS) score from 0 to 6.5 inclusive at screening
  4. Age 18 to 74 years, inclusive at the time of informed consent
  5. Ability and willingness to provide written informed consent and to comply with the requirements of the protocol

Exclusion Criteria:

  1. Clinical relapse onset (including first attack) within 30 days prior to baseline

    Exclusion Criteria Related to Previous or Concomitant Therapy:

  2. Any previous treatment with interleukin 6 (IL-6) inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation or bone marrow transplantation at any time
  3. Any previous treatment with anti-CD20, eculizumab, anti-BLyS monoclonal antibody (e.g., belimumab), any other treatment for prevention of multiple sclerosis (MS) relapse (e.g., interferon, natalizumab, glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate) within 6 months prior to baseline
  4. Any previous treatment with anti-CD4, cladribine, cyclophosphamide or mitoxantrone within 2 years prior to baseline
  5. Treatment with any investigational agent within 3 months prior to baseline

    Exclusions for General Safety:

  6. Pregnancy or lactation.
  7. For patients of reproductive potential, a positive result from a serum pregnancy test at screening, or not willing to use reliable means of contraception (physical barrier [patient or partner] in conjunction with a spermicidal product, contraceptive pill, patch, injectables, intrauterine device or intrauterine system) during the treatment period and for at least 3 months after the last dose of study drug
  8. Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline
  9. Evidence of other demyelinating disease or progressive multifocal leukoencephalopathy (PML)
  10. Evidence of serious uncontrolled concomitant diseases that may preclude patient participation, as described; Other nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine disease, renal/urologic disease, digestive system disease, congenital or acquired severe immunodeficiency
  11. Known active infection (excluding fungal infections of nail beds or caries dentium) within 4 weeks prior to baseline
  12. Evidence of chronic active hepatitis B or C
  13. History of drug or alcohol abuse within 1 year prior to baseline
  14. History of diverticulitis that, in the Investigator's opinion, may lead to increased risk of complications such as lower gastrointestinal perforation
  15. Evidence of active tuberculosis (excluding patients receiving chemoprophylaxis for latent tuberculosis infection)
  16. Evidence of active interstitial lung disease
  17. Receipt of any live or live attenuated vaccine within 6 weeks prior to baseline
  18. History of malignancy within the last 5 years, including solid tumors, hematologic malignancies and in situ carcinoma (except basal cell and squamous cell carcinomas of the skin, or in situ carcinoma of the cervix uteri that have been completely excised and cured)
  19. History of severe allergic reaction to a biologic agent (e.g., shock, anaphylactic reactions)
  20. Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening
  21. History of Stevens-Johnson syndrome
  22. Following laboratory abnormalities at screening*.

    1. White blood cells <3.0 x10^3/microliter (μL)
    2. Absolute neutrophil count <2.0 x 10^3 /μL
    3. Absolute lymphocyte count <0.5 x 10^3 /μL
    4. Platelet count <10 x 10^4 /μL
    5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal.

      • If retest is conducted, the last value of retest before randomization must meet study criteria.

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): NCT02073279


  Show 58 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Chugai Pharmaceutical
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02073279     History of Changes
Other Study ID Numbers: BN40900
SA-309JG ( Other Identifier: Chugai Pharmaceutical )
2015-005431-41 ( EudraCT Number )
First Posted: February 27, 2014    Key Record Dates
Last Update Posted: June 7, 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

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