Clinical trial NCT02073279: Efficacy and Safety Study of Satralizumab (SA237) as Monotherapy to Treat Participants With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) as Monotherapy in Patients With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neuromyelitis Optica (NMO)
NMO Spectrum Disorder (NMOSD)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical
First posted: 2014-02-27
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

   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.

Primary outcomes:
measure: Time to First Protocol-Defined Relapse (TFR) During the Double-Blind (DB) Period
timeFrame: Up to Week 216
Secondary outcomes:
measure: Change From Baseline to Week 24 in Visual Analogue Scale (VAS) for Pain During the DB Period
timeFrame: Baseline, Week 24
measure: Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale During the DB Period
timeFrame: Baseline, Week 24
measure: Relapse-Free Rate During the DB Period
timeFrame: Up to Week 216
measure: Annualized Relapse Rate (ARR) During the DB Period
timeFrame: Up to Week 216
measure: Change From Baseline in Short Form Generic Health Survey (SF-36) Bodily Pain Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Mental Component Summary Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 120
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Change From Baseline in Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period
timeFrame: Baseline up to Week 216
measure: Number of Participants With at Least One Adverse Event in the DB Period
timeFrame: Up to Week 216
measure: Number of Participants With at Least One Serious Adverse Event in the DB Period
timeFrame: Up to Week 216
measure: Number of Participants With Non-Serious Adverse Events of Special Interest in the DB Period
timeFrame: Up to Week 216
measure: Number of Participants With Selected Adverse Events in the DB Period
timeFrame: Up to Week 216
measure: Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period
timeFrame: Baseline and Post-Baseline (up to Week 216)
measure: Serum Satralizumab Concentration During the DB Period
timeFrame: Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter up to Week 204
measure: Serum Interleukin-6 (IL-6) Concentration During the DB Period
timeFrame: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216
measure: Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period
timeFrame: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216
measure: Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period
timeFrame: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216
measure: Percentage of Participants With Anti-Drug Antibodies to Satralizumab in the DB Period
timeFrame: Up to approximately Week 216
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver -; Neurology
state: Colorado
city: Miami
country: United States
facility: University of Miami UHealth Professional Arts Center
state: Florida
city: Vero Beach
country: United States
facility: The MS Center of Vero Beach
state: Florida
city: Columbus
country: United States
facility: Columbus Research and Wellness
state: Georgia
city: Chicago
country: United States
facility: University of Chicago; Neurology
state: Illinois
city: Northbrook
country: United States
facility: Consultants in Neurology Ltd
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Prairie Village
country: United States
facility: MidAmerica Neuroscience Institute
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Wayne State University - Comp Clinic and MS. Center
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: The Neurological Institute PA
state: North Carolina
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: San Antonio
country: United States
facility: UT Medicine San Antonio
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders
state: Wisconsin
city: Dobrich
country: Bulgaria
facility: Medical Help Center EOOD
city: Pleven
country: Bulgaria
facility: MMA-MHAT Pleven - Clinic for Neurology
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', EAD
city: Sofia
country: Bulgaria
facility: MHATNP Sveti Naum EAD
city: Sofia
country: Bulgaria
facility: UMHAT Alexandrovska, EAD
city: Vancouver
country: Canada
facility: MS Clinical Trials Group
state: British Columbia
city: Greenfield Park
country: Canada
facility: Recherche Sepmus Inc.
state: Quebec
city: Montreal
country: Canada
facility: Centre hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Osijek
country: Croatia
facility: Klinicki bolnicki centar Osijek
city: Tbilisi
country: Georgia
facility: LTD Helsicore
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem LTD
city: Tbilisi
country: Georgia
facility: S.Khechinashvili Tbilisi State Medical University Clinic Ne
city: Catania
country: Italy
facility: PO G.Rodolico, AOU Policlinico-Vittorio Emanuele Catania
state: Sicilia
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital - Neurology
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital - Yonsei University Health System - Neurology
city: Kubang Kerian
country: Malaysia
facility: Hospital Universiti Sains Malaysia [Neurology]
state: Kelantan
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Katowice
country: Poland
facility: NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
city: Warszawa
country: Poland
facility: Miedzyleski Szpital Specjalistyczny w Warszawie
city: Guaynabo
country: Puerto Rico
facility: San Juan MS Center
city: Campulung
country: Romania
facility: SC Clubul Sanatatii SRL
city: Taichung
country: Taiwan
facility: China Medical University Healthcare System
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital; Neurology
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital-Neurology
city: Istanbul
country: Turkey
facility: Bilim University Medical Faculty Florence Nightingale Hospital
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivska oblasna klinichna likarnia
state: KIEV Governorate
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivska miska klinichna likarnia №1
state: KIEV Governorate
city: Kiev
country: Ukraine
facility: Kiev National Medical University
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Municipal Foundation of Kyiv Regional Council " Kyiv Region
state: KIEV Governorate
city: Ternopil
country: Ukraine
facility: Reginal clinical psyconeurological hospital
state: KIEV Governorate
city: Vinnytsya
country: Ukraine
facility: Vinnytskyi natsionalnyi medychnyi universytet imeni M.I. Pyr
state: Poltava Governorate
city: Zaporozhya
country: Ukraine
facility: Municipal Establishment "City Clinical Hospital #2; Neurology
state: Poltava Governorate
city: Dnipropetrovsk
country: Ukraine
facility: Miska Klinichna Likarnia №16
state: Tavria Okruha
city: Odesa
country: Ukraine
facility: KU "Odeskyi oblasnyi medychnyi tsentr psykhichnoho zdorovia"
state: Tavria Okruha
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.