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

NCT ID: NCT02073279

Last Updated: 2023-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-05
• Study Completion Date: 2022-01-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Satralizumab

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Satralizumab

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

Interventions

Satralizumab

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

SA237; RG6168

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chugai Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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

Wayne State University - Comp Clinic and MS. Center

Detroit, Michigan, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

The Neurological Institute PA

Charlotte, North Carolina, United States

OhioHealth Research Institute

Columbus, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Central Texas Neurology Consultants

Round Rock, Texas, United States

UT Medicine San Antonio

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders

Milwaukee, Wisconsin, United States

Medical Help Center EOOD

Dobrich, , Bulgaria

MMA-MHAT Pleven - Clinic for Neurology

Pleven, , Bulgaria

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, , Bulgaria

MHATNP Sveti Naum EAD

Sofia, , Bulgaria

UMHAT Alexandrovska, EAD

Sofia, , Bulgaria

MS Clinical Trials Group

Vancouver, British Columbia, Canada

Recherche Sepmus Inc.

Greenfield Park, Quebec, Canada

Centre hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Klinicki bolnicki centar Osijek

Osijek, , Croatia

LTD Helsicore

Tbilisi, , Georgia

Pineo Medical Ecosystem LTD

Tbilisi, , Georgia

S.Khechinashvili Tbilisi State Medical University Clinic Ne

Tbilisi, , Georgia

PO G.Rodolico, AOU Policlinico-Vittorio Emanuele Catania

Catania, Sicily, Italy

Hospital Universiti Sains Malaysia [Neurology]

Kubang Kerian, Kelantan, Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Philippine General Hospital

Manila, , Philippines

NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS

Katowice, , Poland

Miedzyleski Szpital Specjalistyczny w Warszawie

Warsaw, , Poland

San Juan MS Center

Guaynabo, , Puerto Rico

SC Clubul Sanatatii SRL

Campulung Muscel, , Romania

Korea University Anam Hospital - Neurology

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Severance Hospital - Yonsei University Health System - Neurology

Seoul, , South Korea

China Medical University Healthcare System

Taichung, , Taiwan

National Cheng Kung University Hospital; Neurology

Tainan City, , Taiwan

Taipei Veterans General Hospital-Neurology

Taipei, , Taiwan

Bilim University Medical Faculty Florence Nightingale Hospital

Istanbul, , Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Ivano-Frankivska oblasna klinichna likarnia

Ivano-Frankivsk, KIEV Governorate, Ukraine

Ivano-Frankivska miska klinichna likarnia №1

Ivano-Frankivsk, KIEV Governorate, Ukraine

Kiev National Medical University

Kiev, KIEV Governorate, Ukraine

Municipal Foundation of Kyiv Regional Council " Kyiv Region

Kyiv, KIEV Governorate, Ukraine

Reginal clinical psyconeurological hospital

Ternopil, KIEV Governorate, Ukraine

Vinnytskyi natsionalnyi medychnyi universytet imeni M.I. Pyr

Vinnytsia, Poltava Governorate, Ukraine

Municipal Establishment "City Clinical Hospital #2; Neurology

Zaporozhya, Poltava Governorate, Ukraine

Miska Klinichna Likarnia №16

Dnipropetrovsk, Tavria Okruha, Ukraine

KU "Odeskyi oblasnyi medychnyi tsentr psykhichnoho zdorovia"

Odesa, Tavria Okruha, Ukraine

Countries

United States; Bulgaria; Canada; Croatia; Georgia; Italy; Malaysia; Philippines; Poland; Puerto Rico; Romania; South Korea; Taiwan; Turkey (Türkiye); Ukraine

References

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.

Reference Type: DERIVED

PMID: 40743487 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40288333 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36724181 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36007339 (View on PubMed)

Traboulsee A, Greenberg BM, Bennett JL, Szczechowski L, Fox E, Shkrobot S, Yamamura T, Terada Y, Kawata Y, Wright P, Gianella-Borradori A, Garren H, Weinshenker BG. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020 May;19(5):402-412. doi: 10.1016/S1474-4422(20)30078-8.

Reference Type: DERIVED

PMID: 32333898 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SA-309JG

Identifier Type: OTHER

Identifier Source: secondary_id

2015-005431-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BN40900

Identifier Type: -

Identifier Source: org_study_id