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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm, 3- Period Study to assess the Efficacy and Safety of a New Formulation of Oral Cladribine compared with Placebo in Participants with Generalized Myasthenia Gravis(MyClad)

Efficacy and Safety of a New Formulation of Oral Cladribine Compared with Placebo in Participants with Generalized Myasthenia Gravis (MyClad)

Ishii Kyoko

Merck Biopharma Co., Ltd.

1-3-1 Azabudai, Minato-ku, Tokyo

MBJ_clinicaltrial_information@merckgroup.com

Ishii Kyoko

Merck Biopharma Co., Ltd.

1-3-1 Azabudai, Minato-ku, Tokyo

+81-3-4316-8010

MBJ_clinicaltrial_information@merckgroup.com

Recruiting

June. 17, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Adults of:18 years of age at the time of signing the informed consent.
- Diagnosis of Myasthenia Gravis with generalized muscle weakness, meeting clinical criteria for Myasthenia Gravis Foundation of America Class II to !Va classification.
- In participants positive for Acetylcholine receptor antibody (anti- AChR) or muscle-specific kinase antibody(anti-MuSK)
- In participants that are autoantibody seronegative and participants who are positive for anti-low-density lipoprotein receptor- related protein 4 antibodies (anti-LRP4)
- Has a Screening and Baseline MG-ADL score more than or equal to (>=) 6 with at least 50 percentage(%) of the total score due to non- ocular symptoms
- If treated with oral corticosteroids: should be on a stable daily dose for at least 4 weeks before randomization. In such case, the daily dose of oral steroids should not exceed 20 milligrams(mg)/day for prednisone/ prednisolone or 16 mg/day for methylprednisolone
- If treated with acetylcholinesterase inhibitor should be on a stable daily dose for at least 4 weeks before randomization
- Have a body weight >= 40 kilograms
- Other protocol defined inclusion criteria could apply

- Immunologic disorder other than MG or any other condition requiring chronic oral, intravenous, intramuscular, or intraarticular corticosteroid therapy. Well-controlled thyroid disease, as per the Treating Investigator or the participants regular treating physician recorded in the source documents, is not exclusionary
- Molecularly characterized or suspected congenital myasthenic
syndrome, Lambert-Eaton myasthenic syndrome, inherited myopathy, muscular dystrophy, acquired myopathy or any other neurologic or systematic disease that mimics MG muscular weakness
- Active, clinically significant viral, bacterial, or fungal infection, including brain MRI findings consistent with signs of infection such as PML, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks before or during Screening, or completion of oral antiinfectives within 2 weeks before or during Screening, or a history of recurrent infections (i.e. 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary.
- Has a history of or current diagnosis of active tuberculosis (TB)
- Active malignancy, or history of cancer
- Treatment with nonsteroidal immunosuppressants, used in gMG, such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus within 4 weeks prior to randomization
- Treatment with eculizumab, rozanolixizumab efgartigimod, ravulizumab, or zilucoplan within 8 weeks prior to randomization
- History of thymectomy within 6 months prior to Screening.
- History of generalized seizures (except for history of infantile febrile seizures).
- Negative for Varicella Zoster Virus antibodies at screening.
- Other protocol defined exclusion criteria could apply

Both

Generalized Myasthenia Gravis

This study is divided into 3 periods: the double-blind placebo control (DBPC) pivotal period, and 2 extensions, the blinded extension (BE) and the retreatment (RT) period. Participants will be randomly assigned in a ratio of 1:1:1 to 3 arms.
Placebo Arm:
- DBPC Period: Participants will be administered with Placebo, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5.
- BE Period: Participants initially randomized to placebo matched to cladribine in DBPC period will receive cladribine Low Dose or High Dose, orally as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated if clinically justified with placebo matched to cladribine.
- RT Period: Participants requiring retreatment with cladribine Low Dose or High Dose or retreated with cladribine supplemental dose if clinically justified.
Cladribine Low Dose Arm:
- DBPC Period: Participants will be administered with cladribine Low Dose, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5.
- BE Period: Participants initially randomized to cladribine Low Dose in DBPC period will receive placebo matched to cladribine as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated with cladribine supplemental dose if clinically justified.
- RT Period: Participants requiring retreatment with cladribine Low Dose regimen and/or supplemental dose will receive the selected dose of cladribine if clinically justified.
Cladribine High Dose Arm:
- DBPC Period: Participants will be administered cladribine High Dose, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5.
- BE Period: Participants initially randomized to cladribine High Dose in DBPC period will receive placebo matched to cladribine as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated with cladribine supplemental dose if clinically justified.
- RT Period: Participants requiring retreatment with cladribine High Dose regimen and/or supplemental dose will receive the selected dose of cladribine
if clinically justified.

Change from Baseline in Myasthenia Gravis - Activities of Daily Living (MG- ADL) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

+81-3-6779-8166

Mar. 28, 2024

Yes

Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21 Supporting Information: - Study Protocol - Statistical Analysis Plan (SAP) - Clinical Study Report (CSR) - Analytic Code Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal. URL: http://bit.ly/IPD21

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