Phase 3
N=95
Efficacy and Safety Study of Satralizumab (SA237) as Monotherapy to Treat Participants With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)
Neuromyelitis Optica (NMO) · NMO Spectrum Disorder (NMOSD)
Bottom Line
View on ClinicalTrials.gov: NCT02073279 ↗Enrolled (actual)
95
Serious AEs
15.1%
Results posted
Dec 2020
Primary outcome: Primary: Time to First Protocol-Defined Relapse (TFR) During the Double-Blind (DB) Period — 128.3; NA weeks — p=0.0184
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Satralizumab (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to First Protocol-Defined Relapse (TFR) During the Double-Blind (DB) Period |
128.3; NA | 0.0184 sig |
| SECONDARY Change From Baseline to Week 24 in Visual Analogue Scale (VAS) for Pain During the DB Period |
27.563; 31.661; -5.949; -2.735 | 0.4436 |
| SECONDARY Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale During the DB Period |
29.656; 30.590; 3.602; 5.709 | 0.1824 |
| SECONDARY Relapse-Free Rate During the DB Period |
74.87; 88.89; 71.61; 85.71; 61.85; 79.37 | — |
| SECONDARY Annualized Relapse Rate (ARR) During the DB Period |
0.41; 0.17 | — |
| SECONDARY Change From Baseline in Short Form Generic Health Survey (SF-36) Bodily Pain Domain Scores at 24 Week Intervals During the DB Period |
42.86; 43.20; -0.89; -0.13; 1.75; 1.36 | — |
| SECONDARY Change From Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period |
39.43; 39.72; -0.52; 0.49; 1.85; 1.01 | — |
| SECONDARY Change From Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period |
42.86; 46.78; 0.79; 1.84; -0.58; 2.67 | — |
| SECONDARY Change From Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period |
38.70; 39.48; 2.20; 1.96; 2.34; 3.33 | — |
| SECONDARY Change From Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period |
42.24; 42.07; -1.57; 3.87; 0.78; 2.73 | — |
| SECONDARY Change From Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period |
37.86; 37.43; 3.14; 3.52; 4.12; 5.01 | — |
| SECONDARY Change From Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period |
42.93; 41.01; 1.76; 2.42; 0.56; 2.62 | — |
| SECONDARY Change From Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period |
40.72; 46.02; 1.49; 2.33; 4.79; 4.15 | — |
| SECONDARY Change From Baseline in SF-36 Mental Component Summary Scores at 24 Week Intervals During the DB Period |
44.03; 46.43; -0.28; 2.89; 0.09; 2.63 | — |
| SECONDARY Change From Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period |
38.89; 38.59; 1.78; 1.05; 3.57; 2.85 | — |
| SECONDARY Change From Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period |
0.7153; 0.6881; 0.0031; 0.0188; 0.0016; 0.0244 | — |
| SECONDARY Change From Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period |
0.1442; 0.1355; 0.0030; 0.0040; 0.0142; 0.0115 | — |
| SECONDARY Change From Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period |
1.66; 1.97; -0.05; -0.04; 0.00; -0.13 | — |
| SECONDARY Change From Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period |
19.43; 11.32; 0.00; 1.50; -2.83; -3.00 | — |
| SECONDARY Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period |
3.66; 3.92; -0.03; -0.24; -0.06; -0.32 | — |
| SECONDARY Change From Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period |
0.560; 0.449; 0.456; 0.545; -0.058; 0.039 | — |
| SECONDARY Change From Baseline in Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period |
44.3; 44.4; 24.6; 22.6; 17.5; 14.9 | — |
| SECONDARY Number of Participants With at Least One Adverse Event in the DB Period |
24; 58 | — |
| SECONDARY Number of Participants With at Least One Serious Adverse Event in the DB Period |
5; 12 | — |
| SECONDARY Number of Participants With Non-Serious Adverse Events of Special Interest in the DB Period |
0; 0 | — |
| SECONDARY Number of Participants With Selected Adverse Events in the DB Period |
14; 34; 3; 6; 5; 3 | — |
| SECONDARY Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period |
0; 9; 1; 3 | — |
| SECONDARY Serum Satralizumab Concentration During the DB Period |
145.13; 8099.70; 14602.50; 22564.32; 20991.43; 14864.35 | — |
| SECONDARY Serum Interleukin-6 (IL-6) Concentration During the DB Period |
3.66; 3.49; 5.90; 30.14; 5.41; 51.53 | — |
| SECONDARY Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period |
31.88; 33.18; 32.72; 396.49; 44.79; 509.21 | — |
| SECONDARY Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period |
3.08; 4.95; 3.51; 0.93; 3.45; 0.82 | — |
| SECONDARY Percentage of Participants With Anti-Drug Antibodies to Satralizumab in the DB Period |
71.4 | — |
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.
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
- Evidence of other demyelinating disease or progressive multifocal leukoencephalopathy (PML)
- Evidence of serious uncontrolled concomitant diseases that may preclude participant 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
- Known active infection (excluding fungal infections of nail beds or caries dentium) within 4 weeks prior to baseline
- Evidence of chronic active hepatitis B or C
- History of drug or alcohol abuse within 1 year prior to baseline
- History of diverticulitis that, in the Investigator's opinion, may lead to increased risk of complications such as lower gastrointestinal perforation
- Evidence of active tuberculosis (excluding participants receiving chemoprophylaxis for latent tuberculosis infection)
- Evidence of active interstitial lung disease
- Receipt of any live or live attenuated vaccine within 6 weeks prior to baseline
- 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 th
Data sourced from ClinicalTrials.gov (NCT02073279). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.