E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) |
|
E.1.1.1 | Medical condition in easily understood language |
MOGAD is a recently coined neuro-inflammatory condition that preferentially causes demyelinating inflammation in the optic nerve but can also cause inflammation in the spinal cord and brain. |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10075688 |
E.1.2 | Term | Autoimmune demyelinating disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of satralizumab compared with placebo based on time from randomization to the first occurrence of an adjudicated MOGAD relapse in the double-blind (DB) treatment period |
|
E.2.2 | Secondary objectives of the trial |
●To evaluate the efficacy of satralizumab compared with placebo based on rate of adjudicated MOGAD relapses, presence of active lesions on magnetic resonance imaging (MRI) of the neuroaxis, rescue therapy use, inpatient hospitalizations, and proportion of relapse-free participants at 6-month intervals ●To evaluate the safety of satralizumab compared with placebo
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Participants who are aged >=12 years at the time of signing Informed Consent Form ● Confirmed diagnosis of MOGAD with a history of >=1 MOGAD relapse in the 12 months prior to screening or >=2 attacks in the 24 months prior to screening ● Expanded Disability Status Scale (EDSS) score of 0-6.5 at screening ● Best corrected visual acuity (BCVA) better than 20/800 in both eyes at screening ● Participants receiving either no ongoing chronic immunosuppressant treatment (IST) for MOGAD at the time of screening or receiving ongoing treatment with azathioprine (AZA), mycophenolate mofetil (MMF), oral corticosteroids (OCS) prior to and at the time of screening ● No contraindications to rescue treatments ● No contraindications to MRI ● For women of childbearing potential: participants who agree to remain abstinent or use adequate contraception during the treatment period and for at least 3 months after the final dose of satralizumab
|
|
E.4 | Principal exclusion criteria |
● Presence of aquaporin-4-antibodies (AQP4-IgG) in the serum ● History of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis ● Any concomitant disease other than MOGAD that may require treatment with ISTs or OCS or intravenous (IV) corticosteroids at doses >20 mg prednisone equivalent per day for >21 days during the study Exclusion Criteria Related to Previous or Concomitant Therapy ● Intravenous immunoglobulins (IVIg) within 4 weeks prior to screening ● Plasma exchange (PLEX) within 4 weeks prior to screening ● OCS, AZA or MMF within 4 weeks prior to screening (if not continued as concomitant IST in the study) ● Tacrolimus or cyclosporine within 6 weeks prior to screening ● B-cell depleting agents, including rituximab (RTX) and ocrelizumab, within 6 months prior to baseline ● Methotrexate within 3 months prior to screening ● Neonatal Fc receptor antagonists within 6 months prior to screening ● IV cyclophosphamide within 6 months prior to screening ● Complement inhibitors within 6 months prior to screening ● Glatiramer acetate and IFN-β within 1 month prior to screening ● Fumarates within 2 months prior to screening ● Teriflunomide within 2 years prior to screening ● Other MS disease-modifying treatments within 6 months prior to screening ● IL-6 inhibitory therapy at any time ● Total body irradiation, bone marrow transplantation, and autologous hematopoietic stem cell transplantation at any time ● T-cell depleting agents, including but not limited to alemtuzumab, at any time ● Anti-B-lymphocyte stimulator monoclonal antibody at any time ● Cladribine, mitoxantrone, or oral cyclophosphamide at any time ● Treatment with any investigational agent within 24 weeks or 5 drug-elimination half-lives of the investigational drug prior to screening General Safety Exclusion Criteria ● Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of satralizumab ● Participants with active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection at baseline ● Participants with evidence of latent or active tuberculosis (excluding patients receiving chemoprophylaxis for latent tuberculosis infection) ● Participants with positive screening tests for hepatitis B and C ● Receipt of live or live attenuated vaccine within 6 weeks prior to baseline ● History of severe allergic reaction to a biologic agent
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Time from randomization to the first occurrence of a MOGAD relapse in the DB treatment period, as determined by an adjudication committee (CEC) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 44 months |
|
E.5.2 | Secondary end point(s) |
1. Rate of adjudicated MOGAD relapses 2. Active lesions on MRI of the neuroaxis (Gd-enhancing or new/enlarging T2 hyperintense lesions measured across the optic nerve, the spinal cord and the brain, including brainstem and cerebellum) 3. Proportion of participants receiving rescue therapy 4. Rate of inpatient hospitalizations (defined as more than an overnight stay, excluding those for elective procedures) 5. Proportion of relapse-free participants at 6-month intervals 6. Incidence, seriousness and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) 7. Change from baseline in targeted vital signs 8. Change from baseline in targeted electrocardiogram (ECG) parameters 9. Change from baseline in targeted clinical laboratory test results 10. Change from baseline in suicidality, as determined by Columbia-Suicide Severity Rating Scale 11. Change from baseline in weight
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Up to approximately 44 months 6-11. Baseline to up to approximately 44 months
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
China |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The DB treatment period of the study will end when the total number of participants with adjudicated relapses reaches 28, with the CCOD defined as the date 12 weeks after the RA visit for the 28th adjudicated relapse or the RFA visit of the participant with the 28th adjudicated relapse, whichever occurs later. The end of the OLE treatment period is expected to be approximately 2 years after the end of the DB treatment period. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |