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

Phase 3CompletedNCT02073279

Hoffmann-La Roche95 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Neuromyelitis Optica (NMO)NMO Spectrum Disorder (NMOSD)

Interventions

SatralizumabDRUG

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

PlaceboDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participants 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 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 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 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 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 participants 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.

Locations (58)

Outcomes

Primary Outcomes

Time to First Protocol-Defined Relapse (TFR) During the Double-Blind (DB) Period

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.

Time frame: Up to Week 216

Secondary Outcomes

Change From Baseline to Week 24 in Visual Analogue Scale (VAS) for Pain During the DB Period

The VAS is a subjective measure of pain consisting of a 100 mm line with two endpoints representing 0 = "no pain" and 100 = "pain as bad as it could be". Participants rated 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 was measured with a ruler giving a pain score out of 100. A higher score indicated more pain and lower scores reflected a better health state. A negative change from baseline indicates an improvement. ANCOVA was used for analysis to report the adjusted mean and standard error (SE).

Time frame: Baseline, Week 24

Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale During the DB Period

The FACIT Fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. As each of the 13 items of the scale ranges from 0-4, the range of possible scores was computed using FACIT scoring algorithm as 0-52, where 0 is the worst possible score and 52 the best which indicated less fatigue. A positive change from baseline indicates an improvement.

Data from ClinicalTrials.gov

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University of Colorado Denver -; Neurology

Aurora, Colorado, United States

University of Miami UHealth Professional Arts Center

Miami, Florida, United States

The MS Center of Vero Beach

Vero Beach, Florida, United States

Columbus Research and Wellness

Columbus, Georgia, United States

University of Chicago; Neurology

Chicago, Illinois, United States

Consultants in Neurology Ltd

Northbrook, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

MidAmerica Neuroscience Institute

Prairie Village, Kansas, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

...and 48 more locations

Time frame: Baseline, Week 24

Relapse-Free Rate During 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 onsets within 30 days of one another, they were counted as 1), and onset date used in analysis was the date of first relapse.

Time frame: Up to Week 216

Annualized Relapse Rate (ARR) During the DB Period

The ARR is calculated as the total number of participants with adjudicated PDRs experienced divided by the patient-years at risk. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological NMO or 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 (2 relapses with onset days in 30 days of one another was counted as 1 relapse), onset date used in analysis was the date of first relapse.

Time frame: 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

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.