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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Healthcare KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Nov 2024 → ongoing

Decision date (initial)

2025-02-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Merck Healthcare KGaA

External identifiers

EU CT number

2023-507746-83-00

ClinicalTrials.gov

NCT06463587

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the clinical efficacy of cladribine capsules (high and low doses) on gMG relative to placebo.

Secondary objectives 4

1. To evaluate the efficacy of cladribine capsules in the treatment of gMG relative to placebo.
2. To assess the duration of the effect of the initial cladribine full dose.
3. To assess the safety of cladribine capsules on gMG.
4. To characterize the PK of the new oral cladribine formulation in gMG in the rich PK sampling group.

Conditions and MedDRA coding

Generalized Myasthenia Gravis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Pharmaceuticals And Medical Devices Agency, National Medical Products Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000383-PIP04-23

Plan to share IPD

Yes

IPD plan description

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. "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) "
2. Has a Screening and Baseline MG-ADL score more than or equal to (>=) 6 with at least 50 percent (%) of the total score due to non-ocular symptoms. Screening and Baseline MG-ADL scores must be stable. The difference between the screening and Baseline scores should not be more than 2 and there should be no reported MG exacerbation during the screening period.
3. If treated with oral corticosteroids: should be on a stable daily dose for at least 3 months prior to and during screening. 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.
4. If treated with acetylcholinesterase inhibitor should be on a stable daily dose for at least 3 months prior and during screening..
5. Have a body weight >= 40 kilograms.
6. Other protocol defined inclusion criteria could apply.

Exclusion criteria 17

1. 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.
2. History of thymectomy within 6 months prior to Screening.
3. History of myasthenic crisis in the last 12 months prior to and during screening
4. Applicable for France only: Persons under court protection, persons not affiliated to a social security system, protected adults.
5. Negative for Varicella Zoster Virus antibodies at screening.
6. Other protocol defined exclusion criteria could apply.
7. 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.
8. 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 8 weeks prior or during Screening, or completion of oral anti-infectives within 8 weeks prior or during Screening, or a history of recurrent infections. Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary.
9. Has a history of or current diagnosis of active tuberculosis (TB).
10. Active malignancy, or history of cancer.
11. Treatment with nonsteroidal immunosuppressants, used in gMG, such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus within 4 weeks prior to randomization.
12. History of generalized seizures (except for history of febrile seizures during the participant’s childhood)
13. History of recurrent infections (that is 3 or more infections per year) within the last 2 years
14. Discontinuation of treatment with any non-steroidal immunosuppressants used in gMG, such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus within the last 6 months prior to Screening
15. If treated with non-steroidal immunosuppressants for gMG, the dose at Screening should not exceed 50 mg/day for azathioprine, 500 mg/day for mycophenolate mofetil, 1 mg/day for tacrolimus, 50 mg/day for cyclosporine, or 7.5 mg/week for methotrexate
16. Participation in clinical study of any investigational drug within 6 months, or 5 half-lives of the investigational drug used in the previous clinical study prior to randomization, whichever is longer. However, participants with any prior exposure to cladribine may not enter the study regardless of timing of exposure
17. Treatment with eculizumab, rozanolixizumab efgartigimod, ravulizumab, or zilucoplan within 8 weeks prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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.

Secondary endpoints 10

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Healthcare KGaA

Sponsor organisation

Merck Healthcare KGaA

Address

Frankfurter Strasse 250

City

Darmstadt

Postcode

64293

Country

Germany

Scientific contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Third parties 21

Locations

12 EU/EEA countries · 59 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 477 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications