Neuromyelitis optica (NMO) and NMO spectrum disorder (MNOSD) MedDRA version: 20.0 Level: LLT Classification code 10029322 Term: Neuromyelitis optica System Organ Class: 100000004852
Conditions
Interventions
Product Name: Satralizumab (120 mg/vial)
Product Code: Satralizumab (RO5333787/Enspryng/SA237)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Satralizumab (r-INN)
CAS Number: 1535963
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be diagnosed as having either: a. NMO as defined by 2006 criteria*, or b. NMOSD as defined by either of the following Wingerchuk 2007 criteria with anti-AQP4Ab 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‡. ‡ Screening result is based on either the blood sample data collected at screening visit, or the blood sample data collected before the screening visit and measured by Sponsor’s designee for analysis. 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**. a. Azathioprine. b. Mycophenolate mofetil. c. Oral corticosteroids. ** For patients aged 12 to 17 years, either of the following baseline treatments for relapse prevention can be allowed: d. Azathioprine + oral corticosteroids. e. Mycophenolate mofetil + oral corticosteroids. 6. Ability and willingness to provide written informed consent and to comply with the requirements of the protocol. *According to Wingerchuk et al. 2006, a diagnosis of NMO requires all of the following three 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 MS • NMO-IgG seropositive status 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). Inclusion Criterion 2 Clinical evidence of at least 2 documented relapses (including first attack) prior to screening. Are the trial subjects under 18? yes Number of subjects for this age range: 8 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
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. Laboratory exclusion criteria (at screening): 20. Following laboratory abnormalities at screening*. a. White blood cells (WBC) 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). The annotation “*” in the exclusion criterion 20 * If retest is conducted, the last value of retest before baseline mus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary endpoint: Time to first protocol-defined relapse (TFR) in the double-blind period. Specific Primary Outcome Measures (Endpoints) for the Group of Adolescents •Safety assessments - Incidence and severity of AEs, AESIs, SAE and selected AEs - Vital signs (temperature, systolic and diastolic blood pressure and pulse rate), physical examinations, clinical laboratory tests (hematology, chemistry and urinalysis), 12 lead ECGs, suicidality (C-SSRS) •PK, PD and immunogenicity ;Timepoint(s) of evaluation of this end point: Time to first protocol-defined relapse (TFR) in the double-blind period.;Main Objective: To evaluate the efficacy and safety of SA237 compared with placebo in patients with NMO and NMOSD;Secondary Objective: Not applicable | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: i. Change in visual analogue scale (VAS) for pain ii. Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue iii. Change in Short Form generic health survey score (SF-36) iv. Change in EQ-5D v. The proportion of relapse-free patients vi. Annualized relapse rate (ARR) vii. Change in modified Rankin Scale (mRS) viii. Change in Zarit Burden Interview (ZBI) ix. Change in Expanded Disability Status Scale (EDSS) x. Change in visual acuity (Snellen chart) Pharmacodynamic endpoints: IL-6, soluble IL-6 receptor, high sensitivity C-reactive protein, anti-AQP4 antibodies and plasmablasts. PK endpoints: serum SA237 concentrations Immunogenicity endpoints: Incidence of anti-SA237 antibodies Exploratory Endpoint: Additional pain assessment Specific Secondary Outcome Measures (Endpoints) for the Group of Adolescents •TFR •ARR •Change in EDSS score •Change in visual acuity (Snellen chart) •Change in SF-36 score •Change in VAS score for pain •Change in FACIT Fatigue score •Change in EQ-5D score •Change in mRS score •Change in ZBI score ;Timepoint(s) of evaluation of this end point: Selected time points | — |
Countries
France, Germany, Hungary, Italy, Japan, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed