Neuromyelitis Optica Spectrum Disorder (NMOSD) MedDRA version: 21.1 Level: PT Classification code 10077875 Term: Neuromyelitis optica spectrum disorder System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10029322 Term: Neuromyelitis optica System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Enspryng
Pharmaceutical Form: Solution for infusion in pre-filled syringe
INN or Proposed INN: Satralizumab
Current Sponsor code: RO5333787
Concentration unit: mg/ml milligram(s)/millilitr
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age 18 to 74 years, inclusive, at the time of informed consent • Have a diagnosis of AQP4 antibody seropositive NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria • For women of childbearing potential: agreement to either remain abstinent (refrain from heterosexual intercourse) or 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 Cohort 1 (treatment-naïve NMOSD patients) • Confirmation of NMOSD diagnosis with AQP4+ antibodies • Have clinical evidence of at least 1 documented attack or relapse (including first attack) in the last year prior to screening • Naïve to maintenance therapy (disease-modifying therapy [DMT] or immunosuppressive therapy [IST]) Cohort 2 (NMOSD patients with inadequate response to RTX [or its biosimilar]) • Confirmation of NMOSD diagnosis and AQP4+ antibodies in the disease history of the patient • Have a length of disease duration from first symptom of =5 years • History of ongoing treatment with RTX (or its biosimilar) (at least 2 infusions) for NMOSD with a maximum duration of 6 months since last administration prior to enrolment in the study • Ongoing disease activity after last RTX (or its biosimilar) infusion i.e., relapse and/or any new inflammatory event, confirmed by magnetic resonance imaging (MRI) or ophthalmological assessment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 95 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Exclusion criteria for both the cohorts • Inability to complete an MRI • Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of satralizumab • Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline • Evidence of other demyelinating disease, including MS or progressive multifocal leukoencephalopathy (PML) • Evidence of serious uncontrolled concomitant diseases that may preclude patient participation • Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection or other infection (excluding fungal infections of nail beds or caries dentium) at baseline • Infection requiring hospitalization or treatment with intravenous (IV) anti-infective agents within 4 weeks prior to baseline visit • Evidence of chronic active hepatitis B • Evidence of active tuberculosis (TB) • History or laboratory evidence of coagulation disorders • Receipt of a live or live-attenuated vaccine within 6 weeks prior to baseline • Presence or history of malignancy • 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 • History of severe allergic reaction to a biologic agent • Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening • Treatment with any investigational agent within 6 months prior to baseline or 5 drug elimination half-lives of the investigational agent (whichever is longer) Cohort 1 (treatment-naïve NMOSD patients) • Any previous treatment with IL-6 inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation, stem-cell therapy, or bone marrow transplantation • Any previous treatment with eculizumab, belimumab, natalizumab, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, siponimod, or ozanimod • Any previous treatment with anti-CD4, cladribine or mitoxantrone • Any previous treatment with B-cell depleting agents • Any previous treatment with immunosuppressants Cohort 2 (NMOSD patients with inadequate response to RTX) • Discontinued RTX (or biosimilar) treatment due to any other reason than inadequate response to treatment • The following laboratory abnormalities at screening: - White blood cells (WBC) 1.5 times the upper limit of normal (ULN) - Positive serum beta human chorionic gonadotropin (hCG) measured at screening or positive urine dipstick pregnancy test prior to initiation of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To describe the efficacy of satralizumab in patients with aquaporin-4 (AQP4) antibody seropositive NMOSD, either treatment naïve or inadequate responders to previous treatment with rituximab (RTX) (or its biosimilar). ;Secondary Objective: • To describe the evolution of advanced imaging outcomes over time in AQP4 antibody seropositive NMOSD patients treated with satralizumab, either treatment-naïve or inadequate responders to previous treatment with RTX (or its biosimilar) • To describe the safety of satralizumab in patients with aquaporin-4 (AQP4) antibody seropositive NMOSD, either treatment naïve or inadequate responders to previous treatment with rituximab (RTX) (or its biosimilars) ;Primary end point(s): 1. Clinical measures related to disease activity and progression over 96 weeks 2. Proportion of relapse-free patients 3. Annualized relapse rate (ARR) 4. Time to first relapse (TFR) 5. Severity of relapses (hospitalization; use of corticosteroids; rescue therapy; need for plasma exchange; residual disability) 6. Mean change from baseline in expanded disability status scale (EDSS) score over the course of the study 7. Time to onset of confirmed disability progression (CDP) sustained for at least 12 weeks and 24 weeks 8. Change from baseline in the Symbol Digital Modalities Test (SDMT) over the course of the study 9. Change in high-contrast (100%) and low contrast (2.5%) visual acuity using appropriate high-and low-contrast letter acuity (LCLA) charts over the course of the study 10. Change in Visual Functioning Questionnaire-25 (VFQ-25) over the course of the study ;Timepoint(s) of evaluation of this end point: 1-5. Up to Week 96 6-7. Baseline (Day -28 to Day -1) to Week 96 8-10. Baseline (Day -28 to Day -1) to Week 96 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Count, volume and regional distribution of T2-weighted fluid-attenuated inversion recovery (FLAIR) hyperintense lesions, including new and enlarging lesions of the cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum; Fazekas scoring 2. Contrast-enhancing T1-weighted lesions (CEL) of the cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum; optionally meningeal enhancement 3. Diffusion abnormalities of brain and optic nerves 4. Microbleeds of brain and optic nerves 5. Cerebral perfusion alterations 6. Global and regional brain volume loss including basal ganglia, cerebellum and upper cervical spinal cord. Regional brain volume will be assessed only at screening, Week 48 and Week 96 7. New and persisting short T1 inversion recovery (STIR)/proton density (PD) hyperintense lesions and T1-weighted contrast enhancement: Qualitative neuroradiological assessment 8. Quantitative T1 mapping (magnetization-prepared rapid gradient echo sequence [MP2RAGE]) 9. T2*/R* for iron concentration estimation 10. Quantitative diffusion/diffusion tensor imaging (DTI) 11. Change in the retinal nerve fiber layer (RNFL) thickness 12. Change in the ganglion cell plus inner plexiform (GCIP) layer thickness 13. Incidence and severity of adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESIs) 14. Change from Baseline in vital signs, physical examinations, and clinical laboratory tests;Timepoint(s) of evaluation of this end point: 1-5. Up to Week 96 6. At Screening, Weeks 48 and 96 7-10. Up to Week 96 11-12. Baseline (Day -28 to Day -1) to Week 96 13. Up to Week 96 14. Baseline (Day -28 to Day -1) to Week 96 | — |
Countries
Canada, France, Germany, India, Italy, Korea, Republic of, Turkey, United States
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
Outcome results
None listed