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)
Overview
- Phase
- Phase 3
- Intervention
- Satralizumab
- Conditions
- Neuromyelitis Optica (NMO)
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 95
- Locations
- 58
- Primary Endpoint
- Time to First Protocol-Defined Relapse (TFR) During the Double-Blind (DB) Period
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants must be diagnosed as having either neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD), defined as the following:
- •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)
- •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
- •Clinical evidence of at least 1 documented relapse (including first attack) in last 12 months prior to screening
- •Expanded Disability Status Scale (EDSS) score from 0 to 6.5 inclusive at screening
- •Age 18 to 74 years, inclusive at the time of informed consent
- •Ability and willingness to provide written informed consent and to comply with the requirements of the protocol
Exclusion Criteria
- •Clinical relapse onset (including first attack) within 30 days prior to baseline
- •Exclusion Criteria Related to Previous or Concomitant Therapy:
- •Any previous treatment with interleukin 6 (IL-6) inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation or bone marrow transplantation at any time
- •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
- •Any previous treatment with anti-CD4, cladribine, cyclophosphamide or mitoxantrone within 2 years prior to baseline
- •Treatment with any investigational agent within 3 months prior to baseline
- •Exclusions for General Safety:
- •Pregnancy or lactation.
- •For participants of reproductive potential, a positive result from a serum pregnancy test at screening, or not willing to use reliable means of contraception (physical barrier \[participants or partner\] 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
- •Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline
Arms & Interventions
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, up to the end of the study.
Intervention: Satralizumab
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, up to the end of the study.
Intervention: Satralizumab
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, up to the end of the study.
Intervention: Placebo
Outcomes
Primary Outcomes
Time to First Protocol-Defined Relapse (TFR) During the Double-Blind (DB) Period
Time Frame: Up to Week 216
TFR was defined as time from randomization to first occurrence of relapse in the DB period. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). Symptoms had to persist for \>24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred \< 31 days following onset of a protocol-defined relapse were considered part of same relapse (i.e., if 2 relapses had onset days that were 30 days of one another, they were counted only as 1 relapse), and onset date used in analysis was the date of first relapse.
Secondary Outcomes
- Change From Baseline to Week 24 in Visual Analogue Scale (VAS) for Pain During the DB Period(Baseline, Week 24)
- Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale During the DB Period(Baseline, Week 24)
- Annualized Relapse Rate (ARR) During the DB Period(Up to Week 216)
- Change From Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Number of Participants With Non-Serious Adverse Events of Special Interest in the DB Period(Up to Week 216)
- Change From Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period(Baseline up to Week 120)
- Number of Participants With Selected Adverse Events in the DB Period(Up to Week 216)
- Serum Interleukin-6 (IL-6) Concentration During the DB Period(Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216)
- Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period(Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216)
- Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period(Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216)
- Relapse-Free Rate During the DB Period(Up to Week 216)
- Change From Baseline in SF-36 Mental Component Summary Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Number of Participants With at Least One Adverse Event in the DB Period(Up to Week 216)
- Change From Baseline in Short Form Generic Health Survey (SF-36) Bodily Pain Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Number of Participants With at Least One Serious Adverse Event in the DB Period(Up to Week 216)
- Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period(Baseline and Post-Baseline (up to Week 216))
- Serum Satralizumab Concentration During the DB Period(Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter up to Week 204)
- Percentage of Participants With Anti-Drug Antibodies to Satralizumab in the DB Period(Up to approximately Week 216)
- Change From Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)
- Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period(Baseline up to Week 216)