Clinical trial NCT02028884: Efficacy and Safety Study of Satralizumab (SA237) as Add-on Therapy to Treat Participants With Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)
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)
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: 2014-01-07
Enrollment: 85
Sex: ALL
Minimum age (years): 12
Maximum age (years): 74
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Patients 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 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
2. 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
3. EDSS score from 0 to 6.5 inclusive at screening
4. Age 12 to 74 years, inclusive at the time of informed consent
5. 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
6. 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.

Exclusion Criteria:

Exclusion criteria related to previous or concomitant therapy:

1. Any previous treatment with IL-6 inhibitory therapy (e.g. tocilizumab), alemtuzumab, total body irradiation or bone marrow transplantation at any time
2. Any previous treatment with anti-CD20, eculizumab, belimumab, interferon, natalizumab, glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate within 6 months prior to baseline
3. Any previous treatment with anti-CD4, cladribine or mitoxantrone within 2 years prior to baseline
4. Treatment with any investigational agent within 3 months prior to baseline

   Exclusions for general safety:
5. Pregnancy or lactation
6. 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
7. Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline
8. Evidence of other demyelinating disease or progressive multifocal leukoencephalopathy (PML)
9. 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
10. Known active infection (excluding fungal infections of nail beds or caries dentium) within 4 weeks prior to baseline
11. Evidence of chronic active hepatitis B or C
12. History of drug or alcohol abuse within 1 year prior to baseline
13. History of diverticulitis that, in the Investigator's opinion, may lead to increased risk of complications such as lower gastrointestinal perforation
14. Evidence of active tuberculosis (TB; excluding patients receiving chemoprophylaxis for latent TB infection)
15. Evidence of active interstitial lung disease
16. Receipt of any live or live attenuated vaccine within 6 weeks prior to baseline
17. 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)
18. History of severe allergic reaction to a biologic agent (e.g. shock, anaphylactic reactions)
19. Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening
20. Following laboratory abnormalities at screening\*.

    1. White blood cells (WBC) \<3.0 x10\^3/microliter (μL)
    2. Absolute neutrophil count (ANC) \<2.0 x10\^3/μL
    3. Absolute lymphocyte count \<0.5 x10\^3/μL
    4. Platelet count \<10 x 10\^4/μL
    5. 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

Primary outcomes:
measure: Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period
timeFrame: Up to Week 224
Secondary outcomes:
measure: Change From Baseline at Week 24 in the Visual Analogue Scale (VAS) Score for Pain During the DB Period
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score 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 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 168
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 Short Form Generic Health Survey (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 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 EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period
timeFrame: 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 224
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 224
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 224
measure: Serum Interleukin-6 (IL-6) Concentration During the DB Period
timeFrame: Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224
measure: Number of Participants With at Least One Adverse Event in the DB Period
timeFrame: Up to Week 224
measure: Number of Participants With at Least One Serious Adverse Event in the DB Period
timeFrame: Up to Week 224
measure: Number of Participants With Non-Serious Adverse Events of Special Interest in the DB Period
timeFrame: Up to Week 224
measure: Number of Participants With Selected Adverse Events in the DB Period
timeFrame: Up to Week 224
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 224)
measure: Percentage of Participants With Anti-Drug Antibodies to Satralizumab in the DB Period
timeFrame: Up to approximately Week 224
measure: Percentage of Participants With Anti-Drug Antibodies to Satralizumab Overall S237 Period
timeFrame: Up to approximately Week 368
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Strasbourg
country: France
facility: Hopital de Hautepierre CHRU de Strasbourg
city: Berlin
country: Germany
facility: NeuroCure Clinical Research Center (NCRC)
city: Bochum
country: Germany
facility: St. Josef-Hospital, Klinik für Neurologie
city: Düsseldorf
country: Germany
facility: Heinrich-Heine Universitätsklinik Düsseldorf
city: Budapest
country: Hungary
facility: Jahn Ferenc Dél-Pesti Kórház
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea-Universitr di Roma La Sapien
state: Lazio
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
city: Catania
country: Italy
facility: PO G.Rodolico, AOU Policlinico-Vittorio Emanuele Catania
state: Sicilia
city: Cefalu
country: Italy
facility: Fond. Ist. S. Raffaele - giglio
state: Sicilia
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital; Neurology
city: Fukuoka
country: Japan
facility: Kyushu University Hospital; Neurology
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital; Neurology
city: Kagoshima
country: Japan
facility: Kagoshima University Medical And Dental Hospital; Neurology and Geriatorics
city: Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital; Neurology
city: Osaka
country: Japan
facility: Kindai University Hospital; Neurology
city: Sendai
country: Japan
facility: Tohoku University Hospital; Neurology
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital; Neurology
city: Suita
country: Japan
facility: Osaka University Hospital; Neurology
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
city: Katowice
country: Poland
facility: NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
city: Katowice
country: Poland
facility: M.A. - LEK A. M. Maciejowscy SC. Centrum Terapii SM
city: Katowice
country: Poland
facility: Centrum Medyczne Dendryt
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
city: Pozna?
country: Poland
facility: Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu
city: Warsaw
country: Poland
facility: Instytut Psychiatrii i Neurologii
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Klinicznyi
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos; Servicio de Nefrologia
city: Kwei Shen
country: Taiwan
facility: Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Neurology
city: Taichung
country: Taiwan
facility: China Medical University Hospital; Neurology - Taichung
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital; Neurology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital; Neurology
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital-Neurology
city: Kharkiv
country: Ukraine
facility: Kharkivska miska dytiacha likarnia # 5
state: Kharkiv Governorate
city: Dnipropetrovsk
country: Ukraine
facility: KZ "Dnipropetrovska oblasna dytiacha klinichna likarnia" DOR
state: Tavria Okruha
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales; Dept of Neurology
city: Chinnor
country: United Kingdom
facility: John Radcliffe Hospital; Neurosciences
city: London
country: United Kingdom
facility: The National Hospital for Neurology & Neurosurgery
city: London
country: United Kingdom
facility: Great Ormond Street Hospital For Children; Neurology
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: 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.