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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06463587




Registration number
NCT06463587
Ethics application status
Date submitted
11/06/2024
Date registered
18/06/2024

Titles & IDs
Public title
Efficacy and Safety of a New Formulation of Oral Cladribine Compared With Placebo in Participants With Generalized Myasthenia Gravis (MyClad)
Scientific 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)
Secondary ID [1] 0 0
2023-507746-83-00
Secondary ID [2] 0 0
MS700568_0183
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Generalized Myasthenia Gravis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Neurological 0 0 0 0
Other neurological disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Placebo
Treatment: Drugs - Cladribine Low Dose
Treatment: Drugs - Cladribine High Dose

Placebo comparator: 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.

Experimental: 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.

Experimental: 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.


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

Treatment: Drugs: Cladribine Low Dose
Participants will receive cladribine low dose in two courses separated by 4 weeks.

Treatment: Drugs: Cladribine High Dose
Participants will receive a total of cladribine high dose in two courses separated by 4 weeks.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Change from Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Percentage of MG-ADL Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
Timepoint [2] 0 0
At Week 24
Secondary outcome [3] 0 0
Change from Baseline in Myasthenia Gravis Composite (MGC) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Percentage of Quantitative Myasthenia Gravis (QMG) Scale Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period
Timepoint [4] 0 0
At Week 24
Secondary outcome [5] 0 0
Time From Initial Cladribine Full Dose Treatment to First Retreatment of Rescue Treatment up to end of Study
Timepoint [5] 0 0
Up to End of Study (Week 144)
Secondary outcome [6] 0 0
Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
Timepoint [6] 0 0
Up to End of Study (Week 144)
Secondary outcome [7] 0 0
Number of participants with Adverse Events (AEs) by Severity as per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0
Timepoint [7] 0 0
Up to End of Study (Week 144)
Secondary outcome [8] 0 0
Number of Participants with Abnormal Laboratory Variables including Absolute Lymphocyte Count and Vital Signs
Timepoint [8] 0 0
Up to End of Study (Week 144)
Secondary outcome [9] 0 0
Pharmacokinetic (PK) Plasma Concentration of Cladribine
Timepoint [9] 0 0
Pre-dose, 0.25, 1, 2, 3, 4, 6, 8 and 24 hours post-dose
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Baseline, Week 24

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/07/2030
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Gold Coast University Hospital - PARENT - Southport
Recruitment postcode(s) [1] 0 0
- Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
South Carolina
Country [4] 0 0
Argentina
State/province [4] 0 0
Santa Fe
Country [5] 0 0
Argentina
State/province [5] 0 0
Tucuman
Country [6] 0 0
Argentina
State/province [6] 0 0
Ciudad Autonoma Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Cordoba
Country [8] 0 0
Argentina
State/province [8] 0 0
San Juan
Country [9] 0 0
Georgia
State/province [9] 0 0
Tbilisi
Country [10] 0 0
Japan
State/province [10] 0 0
Chiba-Ken
Country [11] 0 0
Japan
State/province [11] 0 0
Hokkaido
Country [12] 0 0
Japan
State/province [12] 0 0
Iwate-Ken
Country [13] 0 0
Japan
State/province [13] 0 0
Kagawa-Ken
Country [14] 0 0
Japan
State/province [14] 0 0
Tokyo-To
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Daegu
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seoul
Country [17] 0 0
Taiwan
State/province [17] 0 0
Kaohsiung
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taichung
Country [19] 0 0
Taiwan
State/province [19] 0 0
Taipei
Country [20] 0 0
United Kingdom
State/province [20] 0 0
South Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
EMD Serono Research & Development Institute, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
EMD Serono Research & Development Institute, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Medical Information
Address 0 0
Country 0 0
Phone 0 0
888-275-7376
Fax 0 0
Email 0 0
eMediUSA@emdserono.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
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
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://bit.ly/IPD21


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06463587