E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myasthenia Gravis which is either due to acetylcholine receptor antibodies (AChR) or muscle specific kinase antibodies (MuSK). |
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E.1.1.1 | Medical condition in easily understood language |
Myasthenia gravis (MG) is a rare autoimmune disorder, caused by binding of antibodies to the acetylcholine receptor (AChR) or functionally related molecules on the postsynaptic neuromuscular junction. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028417 |
E.1.2 | Term | Myasthenia gravis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 assess whether inebilizumab can reduce MG-related disability. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate whether inebilizumab can reduce the frequency of MG exacerbations. - To evaluate whether inebilizumab can improve MG-related quality of life. - To evaluate the safety and tolerability of inebilizumab in MG. - To characterize the pharmacokinetic (PK) profile and immunogenicity of inebilizumab in patients with MG. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
B-cell sub-study: To better understand the effect of inebilizumab, B-cell repertoire profiling prior to and following inebilizumab treatment will be performed
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E.3 | Principal inclusion criteria |
1.Diagnosis of MG with anti-AChR or anti-MuSK antibody. 2.MGFA Clinical Classification Class II, III, or IV. 3.MG-ADL score at the time of screening and randomization between 6 and 10 with > 50% of this score attributed to non-ocular items, or an MG-ADL score ≥ 11. 4.QMG score of 11 or greater at the time of screening and at randomization. 5.Subjects must be on:
a. Corticosteroids only, with no dose increase within 4 weeks prior to randomization, or b. One allowed non-steroidal IST, with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization, or c. Combination of (1) corticosteroids with no dose increase within 4 weeks prior to randomization and (2) one allowed non-steroidal IST with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization.
Allowed ISTs, alone or in combination with corticosteroids, are azathioprine, mycophenolate mofetil, and mycophenolic acid.
6. 9. Females of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective contraception method from the time of screening and for 6 months after the final dose of IP. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception |
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E.4 | Principal exclusion criteria |
8. Thymectomy within ≤ 12 months prior to baseline (Day 1) visit or planned thymectomy during the duration of the RCP. 9. Receipt of the following medications or treatments at any time prior to randomization: a. Alemtuzumab b. Total lymphoid irradiation c. Bone marrow transplant d. T-cell vaccination therapy e. Natalizumab 10. Receipt of rituximab, ocrelizumab, ofatumumab, obinutuzumab, inebilizumab, or any experimental B-cell depleting agent within the 6 months prior to Day 1, unless the subject has a CD19+ B-cell count ≥ 40 cells/µL according to the central laboratory at screening. 11. Receipt of Leflunomide within 1 year prior to Day 1. 12. Receipt within the 3 months prior to Day 1: a. Tocilizumab b. Belimumab c. Eculizumab d. Cyclophosphamide e. Ravulizumab f. Neonatal fragment crystallizable (Fc) receptor (FcRn) blockers (efgartigimod alfa) g. Abatacept h. Etanercept i. Mitoxantrone j. Sirolimus 13. Receipt within the 4 weeks prior to Day 1: a. Cyclosporine (except eye drops) b. Tacrolimus (except topical) (tacrolimus < 3 mg/day is allowed in Japan only; see inclusion criterion 7C) c. Methotrexate d. Intravenous immunoglobulin (IVIg) e. Plasma exchange (PLEX) treatment f. Thalidomide g. Tofacitinib 14. Current use of: a. Corticosteroids (prednisone > 40 mg/day or > 80 mg over a 2-day period, or equivalent dose of other corticosteroids) b. Acetylcholinesterase inhibitors (pyridostigmine > 480 mg/day) or unstable dose in the 2 weeks prior to Day 1 c. Azathioprine > 3 mg/kg/day d. Mycophenolate mofetil > 3 g/day or mycophenolic acid > 1440 mg/day e. Any IST, alone or in combination with corticosteroids, except for azathioprine, mycophenolate mofetil, and mycophenolic acid. 15. Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 half-lives of the investigational treatment, whichever is longer, prior to Day 1. 16. Receipt of a live attenuated vaccine within 4 weeks prior to randomization. Administration of inactivated (killed) vaccines is acceptable.
25. History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV) unless patient is considered to be cured following antiviral therapy and has a HCV viral load below the limit of detection at least 24 weeks after completion of treatment at site or central lab
30. Hospitalization for any reason less than 30 days prior to randomization 31. Current or recent myasthenia gravis exacerbationdeterioration that has not returned to baseline/resolved within at least 30 days prior to randomization.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score at end of the RCP |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints: - Change in Quantitative Myasthenia Gravis (QMG) scores at the end of the RCP. - Proportion of subjects with both (1) ≥ 3-point improvement in MG-ADL at end of RCP and (2) For AChR-Ab+ Population: did not initiate rescue therapy between Week 44 and Week 52 during the RCP; For MuSK-Ab+ population: did not initiate rescue therapy between Week 22 and Week 26 during the RCP - Change in MG-ADL at Week 26 in the AChR-Ab+ population.
Additional secondary endpoints: - Time to first exacerbation. - Change in Myasthenia Gravis Composite (MGC) score. - Change in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score . - Change in Patient Global Impression of Change (PGIC) score. - The safety and tolerability of inebilizumab as measured by the incidence of TEAEs, adverse events of special interest (AESIs), and TESAEs. Laboratory measurements will also be evaluated as part of safety. - PK profile of inebilizumab. - ADA status and titer.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population |
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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 | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
The second part of trial is optional and open label |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Argentina |
Ukraine |
Taiwan |
Belarus |
Brazil |
Canada |
China |
Denmark |
France |
Germany |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Poland |
Russian Federation |
Spain |
Turkey |
United Kingdom |
United States |
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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
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The study will be complete when the last active subject completes the Day 1093 visit of the OLP, discontinues the OLP, or (for patients who have opted out of the OLP) completes the RCP. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 |