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

Phase 3

Recruiting

• Conditions: Generalized Myasthenia Gravis
• Interventions: Drug: Cladribine Low Dose; Other: Placebo; Drug: Cladribine High Dose

• Registration Number: NCT06463587
• Lead Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Brief Summary

The purpose of this clinical study is to determine the efficacy and safety of a new oral cladribine formulation in participants with Generalized Myasthenia Gravis (gMG) in comparison to placebo. It will also investigate the sustained efficacy, the need for retreatment, and the long-term safety of oral cladribine in gMG. An additional component is included to characterize the Pharmacokinetics (PK) of the new cladribine formulation in gMG participants. 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-06-11
• Study First Submitted QC: 2024-06-14
• Study First Posted: 2024-06-18
• Study Start: 2024-06-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-07
• Primary Completion: 2028-05-19
• Study Completion: 2030-07-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• 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 IVa 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Cladribine High Dose	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	Cladribine Low Dose	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.
Placebo	Placebo	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.
Placebo	Cladribine Low Dose	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 High Dose	Cladribine High Dose	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.

Primary Outcome Measures

Name	Time	Method
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	Baseline, Week 24

Secondary Outcome Measures

Name	Time	Method
Percentage of MG-ADL Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period	At Week 24
Change from Baseline in Myasthenia Gravis Composite (MGC) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period	Baseline, Week 24
Change from Baseline in the Revised Myasthenia Gravis Quality of Life - 15 Scale (MG-Qol15r) Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period	Baseline, Week 24
Change from Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period	Baseline, Week 24
Pharmacokinetic (PK) Plasma Concentration of Cladribine	Pre-dose, 0.25, 1, 2, 3, 4, 6, 8 and 24 hours post-dose
Time From Initial Cladribine Full Dose Treatment to First Retreatment of Rescue Treatment up to end of Study	Up to End of Study (Week 144)
Percentage of Quantitative Myasthenia Gravis (QMG) Scale Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period	At Week 24
Number of participants with Adverse Events (AEs) by Severity as per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0	Up to End of Study (Week 144)
Number of Participants with Abnormal Laboratory Variables including Absolute Lymphocyte Count and Vital Signs	Up to End of Study (Week 144)
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)	Up to End of Study (Week 144)

Trial Locations

Locations (35)

The University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

Osaka University Hospital - Dept of Neurology/Stroke Care Unit; 🇯🇵 Suita-shi, Japan

Wielospecjalistyczne Centrum Medyczne Ibismed - Dept of Neurology; 🇵🇱 Zabrze, Poland

Neurology of Central Florida Research Center, LLC; 🇺🇸 Altamonte Springs, Florida, United States

SFM Clinical Research, LLC; 🇺🇸 Boca Raton, Florida, United States

Atrium Health Wake Forest Baptist; 🇺🇸 Winston-Salem, North Carolina, United States

Clinical Trials of South Carolina - Charleston; 🇺🇸 Charleston, South Carolina, United States

Expertia S.A- Mautalen Salud e Investigación; 🇦🇷 Ciudad Autonoma Buenos Aires, Argentina

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI - de Investigaciones Clinicas del área de Cardiología y enfermedades metabólicas asociadas; 🇦🇷 Ciudad Autonoma Buenos Aires, Argentina

Instituto de Investigaciones Metabolicas (IDIM); 🇦🇷 Ciudad Autonoma Buenos Aires, Argentina

Hospital Cordoba; 🇦🇷 Cordoba, Argentina

Fundacion Rosarina de Neurorehabilitacion; 🇦🇷 Rosario, Argentina

INECO Neurociencias Oroño; 🇦🇷 Rosario, Argentina

CER San Juan Centro Polivalente de Asistencia e Inv. Clinica; 🇦🇷 San Juan, Argentina

Centro de Investigaciones Medicas Tucuman; 🇦🇷 San Miguel de Tucuman, Argentina

Gold Coast University Hospital - PARENT; 🇦🇺 Southport, Australia

Ltd. Pineo Medical Ecosystem; 🇬🇪 Tbilisi, Georgia

New Hospitals LLC; 🇬🇪 Tbilisi, Georgia

Aversi Clinic Ltd; 🇬🇪 Tbilisi, Georgia

IUHW Narita Hospital - Dept of Neurology; 🇯🇵 Narita-shi, Chiba-Ken, Japan

Hakodate Municipal Hospital - Dept of Neurology; 🇯🇵 Hakodate-shi, Hokkaido, Japan

General Hanamaki Hospital - Dept of Neurology; 🇯🇵 Hanamaki-shi, Iwate-Ken, Japan

Kagawa University Hospital - Dept of Neurology; 🇯🇵 Kita-gun, Kagawa-Ken, Japan

Tokyo Medical University Hospital - Dept of Neurology; 🇯🇵 Shinjuku-ku, Tokyo-To, Japan

Kyungpook National University Chilgok Hospital; 🇰🇷 Daegu, Korea, Republic of

Keimyung University Dongsan Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul Metropolitan Government Seoul National University Boramae Medical Center; 🇰🇷 Seoul, Korea, Republic of

Kaohsiung Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

Shin Kong Wu Ho-Su Memorial Hospital; 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Royal Hallamshire Hospital - Dept of Neurology; 🇬🇧 Sheffield, South Yorkshire, United Kingdom