Inebilizumab efficacy and safety in adults with myasthenia gravis

Phase 1

Conditions: Myasthenia Gravis which is either due to acetylcholine receptor antibodies (AChR) or muscle specific kinase antibodies (MuSK).
MedDRA version: 21.1Level: PTClassification code 10028417Term: Myasthenia gravisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2020-000949-14-DK

Lead Sponsor: Viela Bio, Inc./Horizon Therapeutics Ireland DAC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 270

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
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 230
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess whether inebilizumab can reduce MG-related<br>disability.;Secondary Objective: - To evaluate whether inebilizumab can reduce the frequency of MG exacerbations.<br>- To evaluate whether inebilizumab can improve MG-related quality of life.<br>- To evaluate the safety and tolerability of inebilizumab in MG.<br>- To characterize the pharmacokinetic (PK) profile and immunogenicity of inebilizumab in patients with MG.;Primary end point(s): Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score at end of the RCP;Timepoint(s) of evaluation of this end point: Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population

Secondary Outcome Measures

Name	Time	Method

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