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

NCT02028884 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: BN408982013-003752-21SA-307JG
• Study Type: interventional
• Target: 85
• Locations: 11 countries
• Sites: 40

Brief 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.

Conditions

Neuromyelitis Optica (NMO); NMO Spectrum Disorder (NMOSD)

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Baseline, Week 24

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

  Baseline, Week 24

• Relapse-Free Rate During the DB Period

  Up to Week 216

• Annualized Relapse Rate (ARR) During the DB Period

  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

Study Arms (2)

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.

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.

Drug: Placebo; Drug: Baseline Treatment

Interventions

Satralizumab DRUG

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

Also known as: SA237, RG6168, RO5333787

Satralizumab + Baseline Treatment

Placebo DRUG

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

Placebo + Baseline Treatment

Baseline Treatment DRUG

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.

Placebo + Baseline Treatment; Satralizumab + Baseline Treatment

Eligibility Criteria

• Age: 12 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical: collaborator

Study Sites (40)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Hopital de Hautepierre CHRU de Strasbourg

Strasbourg, 67091, France

Location

NeuroCure Clinical Research Center (NCRC)

Berlin, 10117, Germany

Location

St. Josef-Hospital, Klinik für Neurologie

Bochum, 44791, Germany

Location

Heinrich-Heine Universitätsklinik Düsseldorf

Düsseldorf, 40225, Germany

Location

Jahn Ferenc Dél-Pesti Kórház

Budapest, 1204, Hungary

Location

Azienda Ospedaliera Sant'Andrea-Universitr di Roma La Sapien

Rome, Lazio, 189, Italy

Location

Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

PO G.Rodolico, AOU Policlinico-Vittorio Emanuele Catania

Catania, Sicily, 95123, Italy

Location

Fond. Ist. S. Raffaele - giglio

Cefalù, Sicily, 90015, Italy

Location

Juntendo University Hospital; Neurology

Bunkyō City, 113-8431, Japan

Location

Kyushu University Hospital; Neurology

Fukuoka, 812-8582, Japan

Location

Fukushima Medical University Hospital; Neurology

Fukushima, 960-1295, Japan

Location

Kagoshima University Medical And Dental Hospital; Neurology and Geriatorics

Kagoshima, 890-8520, Japan

Location

Niigata University Medical and Dental Hospital; Neurology

Niigata, 951-8520, Japan

Location

Kindai University Hospital; Neurology

Osaka, 589-8511, Japan

Location

Tohoku University Hospital; Neurology

Sendai, 980-8574, Japan

Location

Tokyo Women's Medical University Hospital; Neurology

Shinjuku-ku, 162-8666, Japan

Location

Osaka University Hospital; Neurology

Suita, 565-0871, Japan

Location

National Center of Neurology and Psychiatry

Tokyo, 187-8551, Japan

Location

NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS

Katowice, 40-123, Poland

Location

M.A. - LEK A. M. Maciejowscy SC. Centrum Terapii SM

Katowice, 40-571, Poland

Location

Centrum Medyczne Dendryt

Katowice, 40-684, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie

Lublin, 20-954, Poland

Location

Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu

Późna, 60-355, Poland

Location

Samodzielny Publiczny Centralny Szpital Klinicznyi

Warsaw, 02-097, Poland

Location

Instytut Psychiatrii i Neurologii

Warsaw, Poland

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Clinico San Carlos; Servicio de Nefrologia

Madrid, 28040, Spain

Location

Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Neurology

Kwei Shen, 33305, Taiwan

Location

China Medical University Hospital; Neurology - Taichung

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital; Neurology

Tainan, 704, Taiwan

Location

National Taiwan University Hospital; Neurology

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital-Neurology

Taipei, 11217, Taiwan

Location

Kharkivska miska dytiacha likarnia # 5

Kharkiv, Kharkiv Governorate, 61000, Ukraine

Location

KZ "Dnipropetrovska oblasna dytiacha klinichna likarnia" DOR

Dnipropetrovsk, Tavria Okruha, 49100, Ukraine

Location

University Hospital of Wales; Dept of Neurology

Cardiff, CF14 4XW, United Kingdom

Location

John Radcliffe Hospital; Neurosciences

Chinnor, OX3 9DU, United Kingdom

Location

The National Hospital for Neurology & Neurosurgery

London, WC1N 3BG, United Kingdom

Location

Great Ormond Street Hospital For Children; Neurology

London, WC1N 3JH, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 40743487 DERIVED

• Greenberg 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.

  PMID: 40288333 DERIVED

• Kleiter 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.

  PMID: 36724181 DERIVED

• Yamamura 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.

  PMID: 36007339 DERIVED

• Yamamura 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.

  PMID: 31774956 DERIVED

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

satralizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2014
• First Posted: January 7, 2014
• Study Start: February 20, 2014
• Primary Completion: June 6, 2018
• Study Completion: December 23, 2021
• Last Updated: April 18, 2023
• Results First Posted: December 31, 2020

Record last verified: 2023-03

Locations

PL (7); DE (3); HU (1); GB (4); IT (4); ES (2); TW (5); US (1); FR (1); UA (2); JP (10)