INEBILIZUMAB for Myasthenia gravis

Inclusion criteria

• {"criterion_text":"- 1. Diagnosis of MG with anti-AChR or anti-MuSK antibody\n- 2. MGFA Clinical Classification Class II, III, or IV.\n- 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.\n- 4. QMG score ≥ 11 or greater at the time of screening and at randomizatio\n- 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 ≥ 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 ≥ 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.\n- 9. Females of childbearing potential who are sexually active with a nonsterilized 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, or the withdrawal method is not an acceptable methods of contraception"}

Exclusion criteria

• {"criterion_text":"- 8. Thymectomy within the 12 months prior to baseline (Day 1) visit or planned thymectomy during the duration of the RCP.\n- 25. History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV) unless the subject is considered to be cured following antiviral therapy and has an HCV viral load below the limit of detection ≥ 24 weeks after completion of treatment at site or central lab.\n- 30. Hospitalization for any reason < 30 days prior to randomization.\n- 31. Current or recent MG deterioration that has not returned to baseline/resolved within ≥ 30 days prior to randomization.\n- 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 of the following within the 3 months prior to Day 1: a. Tocilizumab, b. Belimumab, c. Eculizumab, d. Cyclophosphamide, e. Ravulizumab, f. Neonatal Fc receptor blockers (efgartigimod alfa) g. Abatacept, h. Etanercept, i. Mitoxantrone, j. Sirolimus\n- 10. Receipt of the following 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) or SC Ig e. PLEX treatment f. Thalidomide g. Tofacitinib\n- 11. 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.\n- 12. 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.\n- 13. Receipt of a live attenuated vaccine within 4 weeks prior to randomization. Administration of inactivated (killed) vaccines is acceptable.\n- 14. 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 ≥ 24 weeks after completion of treatment at site or central lab\n- 15. Hospitalization for any reason < 30 days prior to randomization\n- 16. Current or recent myasthenia gravis exacerbationdeterioration that has not returned to baseline/resolved within at least 30 days prior to randomization."}

Primary endpoints

• {"endpoint_text":"- Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score at Week 26 in the overall study population (ie, the AChR-Ab+ and MuSK-Ab+ populations).","definition_or_measurement_approach":"Change from baseline in MG-ADL score measured at Week 26 in the overall study population (includes AChR-Ab+ and MuSK-Ab+ populations)."}

Secondary endpoints

• {"endpoint_text":"- 1 (Key). Change from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 26 in the overall study population","definition_or_measurement_approach":"Change from baseline in QMG score at Week 26 in overall population."}
• {"endpoint_text":"- 2 (Key). Change from baseline in MG-ADL score at Week 26 in the AChR-Ab+ population.","definition_or_measurement_approach":"Change from baseline in MG-ADL score at Week 26 in the AChR-Ab+ subpopulation."}
• {"endpoint_text":"- 3 (Key). Change from baseline in QMG score at Week 26 in the AChR-Ab+ population","definition_or_measurement_approach":"Change from baseline in QMG score at Week 26 in the AChR-Ab+ subpopulation."}
• {"endpoint_text":"- 4 (Key). Change from baseline in MG-ADL score at Week 26 in the MuSK-Ab+ population.","definition_or_measurement_approach":"Change from baseline in MG-ADL score at Week 26 in the MuSK-Ab+ subpopulation."}
• {"endpoint_text":"- 5 (Key). Change from baseline in QMG score at Week 26 in the MuSK-Ab+ population","definition_or_measurement_approach":"Change from baseline in QMG score at Week 26 in the MuSK-Ab+ subpopulation."}
• {"endpoint_text":"- 1 (Additional). The proportion of subjects with ≥ 3-point improvement in MG-ADL score at Week 26 and no use of rescue therapy between Day 28 and Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 and no use of rescue therapy between Day 28 and Week 52 in the AChR-Ab+ population.","definition_or_measurement_approach":"Proportion of subjects achieving ≥3-point improvement in MG-ADL at specified timepoints without rescue therapy between specified days/weeks."}
• {"endpoint_text":"- 2 (Additional). Change from baseline in MG-ADL score at Week 52 in the AChR-Ab+ population.","definition_or_measurement_approach":"Change from baseline in MG-ADL score at Week 52 in AChR-Ab+ population."}
• {"endpoint_text":"- 3 (Additional). Change from baseline in QMG score at Week 52 in the AChR-Ab+ population","definition_or_measurement_approach":"Change from baseline in QMG score at Week 52 in AChR-Ab+ population."}
• {"endpoint_text":"- 4 (Additional). Change from baseline in Myasthenia Gravis Composite (MGC) score at Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 in the AChR-Ab+ population.","definition_or_measurement_approach":"Change from baseline in MGC score at Weeks 26 and 52 in specified populations."}
• {"endpoint_text":"- 5 (Additional). Change from baseline in Myasthenia Gravis Quality of Life-15, revised score at Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 in the AChR-Ab+ population","definition_or_measurement_approach":"Change from baseline in MG-QOL-15r at Weeks 26 and 52 in specified populations."}
• {"endpoint_text":"- 6 (Additional). Patient Global Impression of Change score at Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 in the AChR-Ab+ population.","definition_or_measurement_approach":"PGIC score at Week 26 (and Week 52 for AChR-Ab+) in specified populations."}
• {"endpoint_text":"- 7 (Additional). Time to first MG exacerbation by Week 26 in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and by Week 52 in the AChR-Ab+ population.","definition_or_measurement_approach":"Time-to-event: time to first MG exacerbation by specified weeks in specified populations."}
• {"endpoint_text":"- 8 (Additional). The safety and tolerability of inebilizumab as measured by the incidence of treatment-emergent adverse events, adverse events of special interest, and treatment-emergent serious adverse events. Laboratory measurements will also be evaluated as part of safety","definition_or_measurement_approach":"Safety endpoints measured by incidence of TEAEs, AESIs, serious AEs, and laboratory evaluations."}
• {"endpoint_text":"- 9 (Additional). The proportion of subjects with steroid tapered to ≤ 5 mg/day at Week 26 for the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and at Week 52 for the AChR-Ab+ population.","definition_or_measurement_approach":"Proportion of subjects achieving steroid taper to ≤5 mg/day at specified weeks in specified populations."}
• {"endpoint_text":"- 10 (Additional). The proportion of subjects in whom steroid dose was reduced by ≥ 50% by Week 26 for the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population and by Week 52 for the AChR-Ab+ population.","definition_or_measurement_approach":"Proportion with ≥50% steroid dose reduction by specified weeks in specified populations."}
• {"endpoint_text":"- 11 (Additional). The proportion of subjects achieving minimal symptom expression, defined as MG-ADL = 0 or 1, at Week 26.","definition_or_measurement_approach":"Proportion achieving MG-ADL = 0 or 1 at Week 26."}
• {"endpoint_text":"- 12 (Additional). Anti-drug antibody status and titer during the study in the overall study population, the AChR-Ab+ population, and the MuSK-Ab+ population.","definition_or_measurement_approach":"Assessment of anti-drug antibody presence and titer during study in specified populations."}

Germany

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

10-05-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

25

France

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

697

Number Of Sites

2

Number Of Participants

25

Spain

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

700

Number Of Sites

3

Number Of Participants

25

Italy

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

20-03-2026

Processing Time Days

701

Number Of Sites

2

Number Of Participants

25

Poland

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

704

Number Of Sites

5

Number Of Participants

25

Primary sponsor

Full Name

Horizon Therapeutics Ireland Designated Activity Company

Organisation Type

Pharmaceutical company

Country Of Registered Address

Ireland

Contract research organisations

Name

Parexel International Limited

Responsibilities

sponsorDuties codes: 8

Name

Medpace Inc.

Responsibilities

sponsorDuties codes: 1,12,2,3,5,6,7,9

Third parties

• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Parexel International Limited","duties_or_roles":"sponsorDuties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"sponsorDuties codes: 1,12,2,3,5,6,7,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yale University School Of Medicine","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Educational Institution"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Non-Pharmaceutical company"}