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

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorMerck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

About this trial

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. Furthermore, in trial interviews will be conducted as a sub-study to MyClad with a sub-set of participants to gain an in depth understanding of the participant cladribine treatment and study experience.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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 i.e. not positive for anti-AChR and anti-MuSK antibodies and participants who are positive for anti-low-density lipoprotein receptor-related protein 4 antibodies (anti-LRP4)

Disqualifiers

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 or chest X-ray findings consistent with signs of infection such as PML or TB, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 8 weeks prior or during Screening, or completion of oral anti-infectives within 8 weeks prior or during Screening. 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) or is currently undergoing treatment for latent TB infection or has an untreated latent TB infection as determined by documented results within 3 months of the Screening Visit of a positive TB skin test .

Trial design

Design model

Sequential

Treatments tested in this trial

  • Placebo

    Other intervention

    Participants will receive placebo matched to cladribine in two courses separated by 4 weeks.

  • Cladribine Low Dose

    Drug

    Participants will receive cladribine low dose in two courses separated by 4 weeks.

  • Cladribine High Dose

    Drug

    Participants will receive cladribine high dose in two courses separated by 4 weeks.

Treatment groups

264 Participants
are divided into 3 treatment groups
Group A: PlaceboPlacebo comparator 3 interventions
Group B: Cladribine Low DoseExperimental treatment 1 intervention
Group C: Cladribine High DoseExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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

Time frame
Baseline, Week 24

Secondary outcomes

1

Change from Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

Time frame
Baseline, Week 24
2

Percentage of MG-ADL Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

MG-ADL responder is defined by achieving \>= 3 points decrease in MG-ADL score.

Time frame
At Week 24
3

Change from Baseline in Myasthenia Gravis Composite (MGC) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

Time frame
Baseline, Week 24
4

Percentage of Quantitative Myasthenia Gravis (QMG) Scale Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

QMG responder is defined by achieving \>= 4 points decrease in QMG score.

Time frame
At Week 24

Other outcomes

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