JOURNAL ONKOLOGIE – STUDIE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Noch nicht rekrutierend

NCT-Nummer:
NCT06463587

Studienbeginn:
Juni 2024

Letztes Update:
21.06.2024

Wirkstoff:
Cladribine Low Dose, Cladribine High Dose

Indikation (Clinical Trials):
Myasthenia Gravis, Muscle Weakness

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Collaborator:
EMD Serono Research & Development Institute, Inc.

Studienleiter

Medical Responsible
Study Director
EMD Serono Research & Development Institute, Inc.

Kontakt

US Medical Information
Kontakt:
Phone: 888-275-7376
E-Mail: eMediUSA@emdserono.com» Kontaktdaten anzeigen

Communication Center
Kontakt:
Phone: +49 6151 72 5200
E-Mail: service@emdgroup.com» Kontaktdaten anzeigen

Studienlocations
(2 von 2)

Please Contact the Communication Center
64293 Darmstadt
(Hessen)
Germany» Google-Maps
Ansprechpartner:
Please Contact the Communication Center
Phone: +49 6151 72 5200
E-Mail: service@emdgroup.com» Ansprechpartner anzeigen

Please Contact U.S. Medical Information
02370 Rockland
United States» Google-Maps
Ansprechpartner:
Please Contact U.S. Medical Information
Phone: 888-275-7376
E-Mail: eMediUSA@emdserono.com» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

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 outcome:

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 (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 (Time Frame - At Week 24)

5. Time From Initial Cladribine Full Dose Treatment to First Retreatment of Rescue Treatment up to end of Study (Time Frame - Up to End of Study (Week 144))

6. Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) (Time Frame - Up to End of Study (Week 144))

7. Number of participants with Adverse Events (AEs) by Severity as per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (Time Frame - Up to End of Study (Week 144))

8. Number of Participants with Abnormal Laboratory Variables including Absolute Lymphocyte Count and Vital Signs (Time Frame - Up to End of Study (Week 144))

9. Pharmacokinetic (PK) Plasma Concentration of Cladribine (Time Frame - Pre-dose, 0.25, 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

10. 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 (Time Frame - Baseline, Week 24)

Studien-Arme

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.

Geprüfte Regime

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

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

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

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!