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

Generalized Myasthenia Gravis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06463587
• Other study ID #: MS700568_0183
• Secondary ID: 2023-507746-83-0
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 17, 2024
• Est. completion date: July 23, 2030

Study information

• Verified date: June 2024
• Source: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: July 23, 2030
• Est. primary completion date: May 19, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

Other:
• Placebo
Participants will receive placebo matched to cladribine in two courses separated by 4 weeks.

Drug:
• Cladribine Low Dose
Participants will receive cladribine low dose in two courses separated by 4 weeks.
• Cladribine High Dose
Participants will receive a total of cladribine high dose in two courses separated by 4 weeks.

Locations

Country	Name	City	State
Germany	Please Contact the Communication Center	Darmstadt
United States	Please Contact U.S. Medical Information	Rockland	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany	EMD Serono Research & Development Institute, Inc.

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period		Baseline, Week 24
Secondary	Percentage of MG-ADL Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period		At Week 24
Secondary	Change from Baseline in Myasthenia Gravis Composite (MGC) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period		Baseline, Week 24
Secondary	Percentage of Quantitative Myasthenia Gravis (QMG) Scale Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period		At Week 24
Secondary	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)
Secondary	Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)		Up to End of Study (Week 144)
Secondary	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)
Secondary	Number of Participants with Abnormal Laboratory Variables including Absolute Lymphocyte Count and Vital Signs		Up to End of Study (Week 144)
Secondary	Pharmacokinetic (PK) Plasma Concentration of Cladribine		Pre-dose, 0.25, 1, 2, 3, 4, 6, 8 and 24 hours post-dose
Secondary	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

External Links

•   Trial Awareness and Transparency website