Neuromyelitis Optica (NMO)Phase 3NCT02028884
Efficacy and Safety Study of Satralizumab (SA237) as Add-on Therapy to Treat Participants With Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)
A Phase 3 study testing Satralizumab and Baseline Treatment in people with Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD), run by Hoffmann-La Roche at 40 sites in 11 countries.
Trial summary
The objective of this study is to evaluate the efficacy, safety, pharmacodynamic, pharmacokinetic, and immunogenic profiles of satralizumab, compared with placebo, in addition to baseline immunosuppressive treatment in participants with NMO and NMOSD. Read more about this study
- Who is it for?
- Ages 12 to 74 years
- Conditions the study is for
- Neuromyelitis Optica (NMO), NMO Spectrum Disorder (NMOSD)
- What is being tested?
- Satralizumab and Baseline Treatment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 40 sitesin 11 countries
- Study dates
- 20 Feb 2014to 23 Dec 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 74 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients 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 the following Wingerchuk 2007 criteria with anti-AQP4 antibody (Ab) seropositive status at screening (i. Idiopathic single or recurrent events of longitudinally extensive myelitis [≥3 vertebral segment spinal cord MRI lesion]; ii. Optic neuritis: recurrent or simultaneous bilateral); For patients aged 12 to 17 years, a minimum of 4 patients should be positive for anti-AQP4Ab status at screening
- Clinical evidence of at least 2 documented relapses (including first attack) in the last 2 years prior to screening, at least one of which has occurred in the 12 months prior to screening
- EDSS score from 0 to 6.5 inclusive at screening
- Age 12 to 74 years, inclusive at the time of informed consent
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- One of the following baseline treatments must be at stable dose as a monotherapy for 8 weeks prior to baseline: Azathioprine; Mycophenolate mofetil; Oral corticosteroids. For participants aged 12 to 17 years, either of the following baseline treatments for relapse prevention can be allowed: Azathioprine + oral corticosteroids; Mycophenolate mofetil + oral corticosteroids
- Ability and willingness to provide written informed consent and to comply with the requirements of the protocol
- For adolescents who may be enrolled after the end of the double-blind period, the inclusion criterion 2 is as follows (other criteria are same): Clinical evidence of at least 2 documented relapses (including first attack) prior to screening.
Who cannot join
- Exclusion criteria related to previous or concomitant therapy:
- Any previous treatment with 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, belimumab, interferon, natalizumab, glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate within 6 months prior to baseline
- Any previous treatment with anti-CD4, cladribine or mitoxantrone within 2 years prior to baseline
- Treatment with any investigational agent within 3 months prior to baseline
- Exclusions for general safety:
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- Pregnancy or lactation
- 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
- 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 patient participation, such as: 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 (TB; excluding patients receiving chemoprophylaxis for latent TB 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 that have been completely excised and cured)
- History of severe allergic reaction to a biologic agent (e.g. shock, anaphylactic reactions)
- Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening
- Following laboratory abnormalities at screening*.
- White blood cells (WBC) <3.0 x10^3/microliter (μL)
- Absolute neutrophil count (ANC) <2.0 x10^3/μL
- Absolute lymphocyte count <0.5 x10^3/μL
- Platelet count <10 x 10^4/μL
- Aspartate aminotransferase (AST) or alanine aminotranferase (ALT) >1.5 times the upper limit of normal (ULN) * If retest is conducted, the last value of retest before randomization must meet study criteria.
- For adolescents who may be enrolled after the end of the double-blind period, the annotation in the exclusion criterion 20 is as follows (other criteria are same): If retest is conducted, the last value of retest before baseline must meet study criteria
Trial locations and contacts
40 sites in 11 countries.
40 sites in 11 countries
Japan10 sites
Juntendo University Hospital; Neurology
Bunkyō City, 113-8431
Kyushu University Hospital; Neurology
Fukuoka, 812-8582
Fukushima Medical University Hospital; Neurology
Fukushima, 960-1295
Kagoshima University Medical And Dental Hospital; Neurology and Geriatorics
Kagoshima, 890-8520
Niigata University Medical and Dental Hospital; Neurology
Niigata, 951-8520
Kindai University Hospital; Neurology
Osaka, 589-8511
Tohoku University Hospital; Neurology
Sendai, 980-8574
Tokyo Women's Medical University Hospital; Neurology
Shinjuku-ku, 162-8666
Osaka University Hospital; Neurology
Suita, 565-0871
National Center of Neurology and Psychiatry
Tokyo, 187-8551
Poland7 sites
NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
Katowice, 40-123
M.A. - LEK A. M. Maciejowscy SC. Centrum Terapii SM
Katowice, 40-571
Centrum Medyczne Dendryt
Katowice, 40-684
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
Lublin, 20-954
Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu
Późna, 60-355
Samodzielny Publiczny Centralny Szpital Klinicznyi
Warsaw, 02-097
Instytut Psychiatrii i Neurologii
Warsaw
Taiwan5 sites
Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Neurology
Kwei Shen, 33305
China Medical University Hospital; Neurology - Taichung
Taichung, 40447
National Cheng Kung University Hospital; Neurology
Tainan, 704
National Taiwan University Hospital; Neurology
Taipei, 100
Taipei Veterans General Hospital-Neurology
Taipei, 11217
Italy4 sites
PO G.Rodolico, AOU Policlinico-Vittorio Emanuele Catania
Catania, Sicily, 95123
Fond. Ist. S. Raffaele - giglio
Cefalù, Sicily, 90015
Ospedale San Raffaele
Milan, Lombardy, 20132
Azienda Ospedaliera Sant'Andrea-Universitr di Roma La Sapien
Rome, Lazio, 189
United Kingdom4 sites
University Hospital of Wales; Dept of Neurology
Cardiff, CF14 4XW
John Radcliffe Hospital; Neurosciences
Chinnor, OX3 9DU
The National Hospital for Neurology & Neurosurgery
London, WC1N 3BG
Great Ormond Street Hospital For Children; Neurology
London, WC1N 3JH
Germany3 sites
NeuroCure Clinical Research Center (NCRC)
Berlin, 10117
St. Josef-Hospital, Klinik für Neurologie
Bochum, 44791
Heinrich-Heine Universitätsklinik Düsseldorf
Düsseldorf, 40225
Spain2 sites
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Clinico San Carlos; Servicio de Nefrologia
Madrid, 28040
Ukraine2 sites
KZ "Dnipropetrovska oblasna dytiacha klinichna likarnia" DOR
Dnipropetrovsk, Tavria Okruha, 49100
Kharkivska miska dytiacha likarnia # 5
Kharkiv, Kharkiv Governorate, 61000
United States1 site
Children's Hospital of Alabama
Birmingham, Alabama, 35233
About this study
Official title: A Multicenter, Randomized, Addition to Baseline Treatment, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) in Patients With Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)
The objective of this study is to evaluate the efficacy, safety, pharmacodynamic, pharmacokinetic, and immunogenic profiles of satralizumab, compared with placebo, in addition to baseline immunosuppressive treatment in participants with NMO and NMOSD.
- Being tested
- Satralizumab, Placebo, Baseline Treatment
- Medical subject headings
- Neuromyelitis Optica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SatralizumabDrug
Also called SA237, RG6168, RO5333787
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).
Baseline TreatmentDrug
As specified in the protocol, one of the following drugs at a stable dose is required as monotherapy for baseline treatment during the double-blind period: azathioprine (AZA); mycophenolate mofetil (MMF); or oral corticosteroids (CS). For participants aged 12 to 17 years at the time of informed consent, baseline treatment with AZA or MMF in combination with oral CS is also permitted. Change or termination of baseline treatment is only permitted during the open-label extension period.
| Study group | Role | What they receive |
|---|---|---|
| Satralizumab + Baseline Treatment | Experimental | Participants randomized to this arm for the double-blind period will receive satralizumab in addition to baseline treatment. The double-blind period ends when either the participant has a treated relapse or the total number of protocol-defined relapses confirmed by the Clinical Endpoint Committee (CEC) reaches 26. In the open-label extension period, the participant will receive (with or without baseline treatment) an SC injection of satralizumab at Weeks 0, 2, and 4, and Q4W thereafter, with the last study drug administration on or before 31 December 2021. Receives: Drug: Satralizumab; Drug: Baseline Treatment |
| Placebo + Baseline Treatment | Placebo comparator | Participants randomized to this arm for the double-blind period will receive placebo in addition to baseline treatment.The double-blind period ends when either the participant has a treated relapse or the total number of protocol-defined relapses confirmed by the Clinical Endpoint Committee (CEC) reaches 26. In the open-label extension period, the participant will receive (with or without baseline treatment) an SC injection of satralizumab at Weeks 0, 2, and 4, and Q4W thereafter, with the last study drug administration on or before 31 December 2021. Receives: Drug: Placebo; Drug: Baseline Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First Protocol-Defined Relapse (TFR) in the Double-Blind 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) as adjudicated by an independent clinical endpoint committee (CEC). 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.
Measured: Up to Week 224
Secondary outcomes (30)
Change From Baseline at Week 24 in the Visual Analogue Scale (VAS) Score 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).
Measured: Baseline, Week 24
Change From Baseline at Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score 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. ANCOVA was used for analysis to report the adjusted mean and SE.
Measured: 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.
Measured: Up to Week 216
Annualized Relapse Rate (ARR) During the DB Period
The ARR is calculated as the total number of participants with relapses 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.
Measured: Up to Week 216
Change From Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period
The mRS is a 7-point disability scale that assesses the degree of disability in participants with neurological impairment. Possible scores range from 0 (no symptoms at all) up to 6 (death). Higher scores reflect increased disability. A negative change from baseline indicates an improvement.
Measured: Baseline up to Week 216
Change From Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period
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. A negative change from baseline indicates an improvement.
Measured: Baseline up to Week 168
Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period
The EDSS is an ordinal scale with values from 0 points (normal neurological examination) to 10 points (death) increasing in half-point increments once an EDSS of 1.0 has been reached. Higher scores represent increased disability. A negative change from baseline indicates an improvement.
Measured: Baseline up to Week 216
Change From Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period
Visual acuity was measured using Snellen 20-foot wall chart and then converted to logMAR visual acuity scoring. Lower values indicate better visual acuity. Data are reported for right eye (OD) and left eye (OS). A negative change from baseline indicates an improvement.
Measured: Baseline up to Week 216
Change From Baseline in Short Form Generic Health Survey (SF-36) Mental Component Summary 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 summary measures and a preference-based health utility index. The component scores were transformed to a 0-100 scale, where higher score indicates better quality of life. A positive change from baseline indicates an improvement.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 Physical Component Summary 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 summary measures and a preference-based health utility index. The component scores were transformed to a 0-100 scale, where higher score indicates better quality of life. A positive change from baseline indicates an improvement.
Measured: Baseline up to Week 216
Change From Baseline in 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.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 General Health 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.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 Mental Health 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.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 Physical Functioning 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.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 Role-Emotional 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.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 Role-Physical 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.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 Social Role Functioning 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.
Measured: Baseline up to Week 216
Change From Baseline in SF-36 Vitality 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.
Measured: Baseline up to Week 216
Change From Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period
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 scores from 5 dimensions are used as input to generate EQ-5D index score using scoring algorithm. The EQ-5D index score is scored on a scale of -0.2 to 1. A higher score reflects a better health state. A positive change from baseline indicates an improvement.
Measured: Baseline up to Week 216
Serum Satralizumab Concentration During the DB Period
Measured: Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter up to Week 224
Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period
Measured: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224
Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period
Measured: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224
Serum Interleukin-6 (IL-6) Concentration During the DB Period
Measured: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224
Number of Participants With at Least One Adverse Event in the DB Period
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
Measured: Up to Week 224
Number of Participants With at Least One Serious Adverse Event in the DB Period
A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Measured: Up to Week 224
Number of Participants With Non-Serious Adverse Events of Special Interest in the DB Period
Non-serious adverse events of special interest for this study included: 1) cases of an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, 2) suspected transmission of an infectious agent by the study treatment.
Measured: Up to Week 224
Number of Participants With Selected Adverse Events in the DB Period
Selected adverse events for this study included: 1) non-serious infections that required treatments with intravenous (IV) antibiotic, antifungal, antiviral, 2) opportunistic infections that required treatments with oral antibiotics, antifungals, or antivirals, 3) injection-related reactions (IRRs; an AE which occured within 24 hours after study treatment injection except where the event was not considered an allergic reaction), and 4) anaphylaxis (an acute allergic/hypersensitivity reaction).
Measured: Up to Week 224
Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period
The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates suicidal ideation or behavior.
Measured: Baseline and Post-Baseline (up to Week 224)
Percentage of Participants With Anti-Drug Antibodies to Satralizumab in the DB Period
Reported here is the percentage of participants with at least one positive anti-drug antibody measurement during the DB period.
Measured: Up to approximately Week 224
Percentage of Participants With Anti-Drug Antibodies to Satralizumab Overall S237 Period
Reported here is the percentage of participants with at least one positive anti-drug antibody measurement during Overall S237 period.
Measured: Up to approximately Week 368
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2014 (estimated)
- Study start20 Feb 2014
- Primary completion6 Jun 2018
- Study completion23 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Neuromyelitis Optica (NMO)Studies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02028884
- Sponsor's protocol ID
- BN40898
- Other IDs
- 2013-003752-21, SA-307JG
- Status last verified
- Mar 2023
- First submitted
- 6 Jan 2014
- Last updated
- 18 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bennett JL, Fujihara K, Saiz A, Traboulsee AL, Greenberg BM, Weinshenker BG, Patti F, Kleiter I, Palace J, De Seze J, Evans R, Blondeau K, Klingelschmitt G, Vodopivec I, Rahim M, Yamamura T. Long-Term Efficacy and Safety of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder From the SAkuraMoon Open-Label Extension Study. Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200450. doi: 10.1212/NXI.0000000000200450. Epub 2025 Jul 31.
PubMed 40743487Greenberg BM, Fujihara K, Weinshenker B, Patti F, Kleiter I, Bennett JL, Palace J, Blondeau K, Burdeska A, Ngwa I, Klingelschmitt G, Triyatni M, Yamamura T. Analysis of infection rates in neuromyelitis optica spectrum disorder: Comparing satralizumab treatment in SAkuraMoon, post-marketing, and US-based health claims data. Mult Scler Relat Disord. 2025 Jul;99:106444. doi: 10.1016/j.msard.2025.106444. Epub 2025 Apr 19.
PubMed 40288333Kleiter I, Traboulsee A, Palace J, Yamamura T, Fujihara K, Saiz A, Javed A, Mayes D, Budingen HV, Klingelschmitt G, Stokmaier D, Bennett JL. Long-term Efficacy of Satralizumab in AQP4-IgG-Seropositive Neuromyelitis Optica Spectrum Disorder From SAkuraSky and SAkuraStar. Neurol Neuroimmunol Neuroinflamm. 2022 Dec 8;10(1):e200071. doi: 10.1212/NXI.0000000000200071. Print 2023 Jan.
PubMed 36724181Yamamura T, Weinshenker B, Yeaman MR, De Seze J, Patti F, Lobo P, von Budingen HC, Kou X, Weber K, Greenberg B. Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar. Mult Scler Relat Disord. 2022 Oct;66:104025. doi: 10.1016/j.msard.2022.104025. Epub 2022 Jul 5.
PubMed 36007339Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, Patti F, Tsai CP, Saiz A, Yamazaki H, Kawata Y, Wright P, De Seze J. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Nov 28;381(22):2114-2124. doi: 10.1056/NEJMoa1901747.
PubMed 31774956
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Addition to Baseline Treatment, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) in Patients With Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)
- ClinicalTrials.gov ID
- NCT02028884
- Acronym / sponsor ID
- BN40898
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical
- Study start
- 20 Feb 2014 (actual)
- Primary completion
- 6 Jun 2018 (actual)
- Study completion
- 23 Dec 2021 (actual)
- First posted
- 7 Jan 2014 (estimated)
- Results
- Posted 31 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to evaluate the efficacy, safety, pharmacodynamic, pharmacokinetic, and immunogenic profiles of satralizumab, compared with placebo, in addition to baseline immunosuppressive treatment in participants with NMO and NMOSD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Satralizumab + Baseline Treatment | Experimental | Drug: Satralizumab, Drug: Baseline TreatmentParticipants randomized to this arm for the double-blind period will receive satralizumab in addition to baseline treatment. The double-blind period ends when either the participant has a treated relapse or the total number of protocol-defined relapses confirmed by the Clinical Endpoint Committee (CEC) reaches 26. In the open-label extension period, the participant will receive (with or without baseline treatment) an SC injection of satralizumab at Weeks 0, 2, and 4, and Q4W thereafter, with the last study drug administration on or before 31 December 2021. |
| Placebo + Baseline Treatment | Placebo comparator | Drug: Placebo, Drug: Baseline TreatmentParticipants randomized to this arm for the double-blind period will receive placebo in addition to baseline treatment.The double-blind period ends when either the participant has a treated relapse or the total number of protocol-defined relapses confirmed by the Clinical Endpoint Committee (CEC) reaches 26. In the open-label extension period, the participant will receive (with or without baseline treatment) an SC injection of satralizumab at Weeks 0, 2, and 4, and Q4W thereafter, with the last study drug administration on or before 31 December 2021. |
Who may qualify
- Ages
- 12 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must be diagnosed as having either neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD), defined as the following:
- Clinical evidence of at least 2 documented relapses (including first attack) in the last 2 years prior to screening, at least one of which has occurred in the 12 months prior to screening
- EDSS score from 0 to 6.5 inclusive at screening
- Age 12 to 74 years, inclusive at the time of informed consent
- One of the following baseline treatments must be at stable dose as a monotherapy for 8 weeks prior to baseline: Azathioprine; Mycophenolate mofetil; Oral corticosteroids. For participants aged 12 to 17 years, either of the following baseline treatments for relapse prevention can be allowed: Azathioprine + oral corticosteroids; Mycophenolate mofetil + oral corticosteroids
Key exclusion criteria (28 listed)
- Any previous treatment with 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, belimumab, interferon, natalizumab, glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate within 6 months prior to baseline
- Any previous treatment with anti-CD4, cladribine or mitoxantrone within 2 years prior to baseline
- Treatment with any investigational agent within 3 months prior to baseline
- Pregnancy or lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SatralizumabAlso: SA237, RG6168, RO5333787Satralizumab will be administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W). | Drug | Satralizumab + Baseline Treatment |
| PlaceboPlacebo will be administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W). | Drug | Placebo + Baseline Treatment |
| Baseline TreatmentAs specified in the protocol, one of the following drugs at a stable dose is required as monotherapy for baseline treatment during the double-blind period: azathioprine (AZA); mycophenolate mofetil (MMF); or oral corticosteroids (CS). For participants aged 12 to 17 years at the time of informed consent, baseline treatment with AZA or MMF in combination with oral CS is also permitted. Change or termination of baseline treatment is only permitted during the open-label extension period. | Drug | Placebo + Baseline Treatment, Satralizumab + Baseline Treatment |
Primary outcome
Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period
Time frame: Up to Week 224
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) as adjudicated by an independent clinical endpoint committee (CEC). 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.
30 secondary outcomes
Change From Baseline at Week 24 in the Visual Analogue Scale (VAS) Score for Pain During the DB Period
Time frame: Baseline, Week 24
Change From Baseline at Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score During the DB Period
Time frame: Baseline, Week 24
Relapse-Free Rate During the DB Period
Time frame: Up to Week 216
Annualized Relapse Rate (ARR) During the DB Period
Time frame: Up to Week 216
Change From Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 168
Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in Short Form Generic Health Survey (SF-36) Mental Component Summary Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Bodily Pain Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Change From Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period
Time frame: Baseline up to Week 216
Serum Satralizumab Concentration During the DB Period
Time frame: Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter up to Week 224
Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period
Time frame: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224
Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period
Time frame: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224
Serum Interleukin-6 (IL-6) Concentration During the DB Period
Time frame: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224
Number of Participants With at Least One Adverse Event in the DB Period
Time frame: Up to Week 224
Number of Participants With at Least One Serious Adverse Event in the DB Period
Time frame: Up to Week 224
Number of Participants With Non-Serious Adverse Events of Special Interest in the DB Period
Time frame: Up to Week 224
Number of Participants With Selected Adverse Events in the DB Period
Time frame: Up to Week 224
Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period
Time frame: Baseline and Post-Baseline (up to Week 224)
Percentage of Participants With Anti-Drug Antibodies to Satralizumab in the DB Period
Time frame: Up to approximately Week 224
Percentage of Participants With Anti-Drug Antibodies to Satralizumab Overall S237 Period
Time frame: Up to approximately Week 368
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40743487Bennett JL, Fujihara K, Saiz A, Traboulsee AL, Greenberg BM, Weinshenker BG, Patti F, Kleiter I, Palace J, De Seze J, Evans R, Blondeau K, Klingelschmitt G, Vodopivec I, Rahim M, Yamamura T. Long-Term Efficacy and Safety of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder From the SAkuraMoon Open-Label Extension Study. Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200450. doi: 10.1212/NXI.0000000000200450. Epub 2025 Jul 31.
- Derived from this study: PubMed 40288333Greenberg BM, Fujihara K, Weinshenker B, Patti F, Kleiter I, Bennett JL, Palace J, Blondeau K, Burdeska A, Ngwa I, Klingelschmitt G, Triyatni M, Yamamura T. Analysis of infection rates in neuromyelitis optica spectrum disorder: Comparing satralizumab treatment in SAkuraMoon, post-marketing, and US-based health claims data. Mult Scler Relat Disord. 2025 Jul;99:106444. doi: 10.1016/j.msard.2025.106444. Epub 2025 Apr 19.
- Derived from this study: PubMed 36724181Kleiter I, Traboulsee A, Palace J, Yamamura T, Fujihara K, Saiz A, Javed A, Mayes D, Budingen HV, Klingelschmitt G, Stokmaier D, Bennett JL. Long-term Efficacy of Satralizumab in AQP4-IgG-Seropositive Neuromyelitis Optica Spectrum Disorder From SAkuraSky and SAkuraStar. Neurol Neuroimmunol Neuroinflamm. 2022 Dec 8;10(1):e200071. doi: 10.1212/NXI.0000000000200071. Print 2023 Jan.
- Derived from this study: PubMed 36007339Yamamura T, Weinshenker B, Yeaman MR, De Seze J, Patti F, Lobo P, von Budingen HC, Kou X, Weber K, Greenberg B. Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar. Mult Scler Relat Disord. 2022 Oct;66:104025. doi: 10.1016/j.msard.2022.104025. Epub 2022 Jul 5.
- Derived from this study: PubMed 31774956Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, Patti F, Tsai CP, Saiz A, Yamazaki H, Kawata Y, Wright P, De Seze J. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Nov 28;381(22):2114-2124. doi: 10.1056/NEJMoa1901747.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
40 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Satralizumab and Baseline Treatment in people with Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD), run by Hoffmann-La Roche at 40 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Japan, Poland, Taiwan, Italy, United Kingdom and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period (time frame: Up to Week 224). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02028884, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.