Clinical trial NCT06463587: Efficacy and Safety of a New Formulation of Oral Cladribine Compared With Placebo in Participants With Generalized Myasthenia Gravis (MyClad)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Generalized Myasthenia Gravis
Keywords: Anti-AChR antibody positive
anti-MuSK antibody positive
anti-LRP4 antibody positive
seronegative gMG
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: EMD Serono Research & Development Institute, Inc.
First posted: 2024-06-18
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change from Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
timeFrame: Baseline, Week 24
measure: Percentage of MG-ADL Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
timeFrame: At Week 24
measure: Change from Baseline in Myasthenia Gravis Composite (MGC) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
timeFrame: Baseline, Week 24
measure: Percentage of Quantitative Myasthenia Gravis (QMG) Scale Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
timeFrame: At Week 24
measure: Time From Initial Cladribine Full Dose Treatment to First Retreatment of Rescue Treatment up to end of Study
timeFrame: Up to End of Study (Week 144)
measure: Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Up to End of Study (Week 144)
measure: Number of participants with Adverse Events (AEs) by Severity as per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0
timeFrame: Up to End of Study (Week 144)
measure: Number of Participants with Abnormal Laboratory Variables including Absolute Lymphocyte Count and Vital Signs
timeFrame: Up to End of Study (Week 144)
measure: Pharmacokinetic (PK) Plasma Concentration of Cladribine
timeFrame: Pre-dose, 0.25, 1, 2, 3, 4, 6, 8 and 24 hours post-dose
measure: 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
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Altamonte Springs
country: United States
facility: Neurology of Central Florida Research Center, LLC
state: Florida
city: Boca Raton
country: United States
facility: SFM Clinical Research, LLC
state: Florida
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Charleston
country: United States
facility: Clinical Trials of South Carolina - Charleston
state: South Carolina
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Expertia S.A- Mautalen Salud e Investigación
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Neurologicas Raul Carrea, FLENI - de Investigaciones Clinicas del área de Cardiología y enfermedades metabólicas asociadas
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas (IDIM)
city: Cordoba
country: Argentina
facility: Hospital Cordoba
city: Rosario
country: Argentina
facility: Fundacion Rosarina de Neurorehabilitacion
city: Rosario
country: Argentina
facility: INECO Neurociencias Oroño
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Medicas Tucuman
city: Southport
country: Australia
facility: Gold Coast University Hospital - PARENT
city: Tbilisi
country: Georgia
facility: Ltd. Pineo Medical Ecosystem
city: Tbilisi
country: Georgia
facility: New Hospitals LLC
city: Tbilisi
country: Georgia
facility: Aversi Clinic Ltd
city: Narita-shi
country: Japan
facility: IUHW Narita Hospital - Dept of Neurology
state: Chiba-Ken
city: Hakodate-shi
country: Japan
facility: Hakodate Municipal Hospital - Dept of Neurology
state: Hokkaido
city: Hanamaki-shi
country: Japan
facility: General Hanamaki Hospital - Dept of Neurology
state: Iwate-Ken
city: Kita-gun
country: Japan
facility: Kagawa University Hospital - Dept of Neurology
state: Kagawa-Ken
city: Shinjuku-ku
country: Japan
facility: Tokyo Medical University Hospital - Dept of Neurology
state: Tokyo-To
city: Suita-shi
country: Japan
facility: Osaka University Hospital - Dept of Neurology/Stroke Care Unit
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Seoul
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government Seoul National University Boramae Medical Center
city: Zabrze
country: Poland
facility: Wielospecjalistyczne Centrum Medyczne Ibismed - Dept of Neurology
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Shin Kong Wu Ho-Su Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital - Dept of Neurology
state: South Yorkshire
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc.
name: Medical Responsible
role: STUDY_DIRECTOR
References: