Cladribine therapy in Myasthenia

Phase 1

• Conditions: Myasthenia gravis; MedDRA version: 21.1Level: PTClassification code 10028417Term: Myasthenia gravisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2020-005762-34-PL
• Lead Sponsor: Medical University of Lublin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-03-04
• Last Update Posted: 20 November 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

GENERAL CRITERIA:
1. Age > 18 years (no border).
2. Obtaining informed consent for the patient's participation in the entry.
3. The characteristic clinical picture of myasthenia gravis with non-painful movement of typical striated muscle groups with the intensity of professional development changing throughout the day.
4. Increased cut-off titer of anti-acetylcholine receptor (anti-AchR-ab) or muscle tyrosine kinase (anti-MUSK-ab) involved in the pathogenesis of myasthenia gravis (historical result: untimed).
5. The known status of thymus pathology based on the chest radiological examination (CT) (historical up to 5 years prior to qualifying visit or performed at qualifying visit) and / or the hist-path results of the removed thymus if the patient underwent a thymectomy.
6. Corticosteroid dose stabilised = 4 weeks prior to randomisation and a minimum 4-week withdrawal period from other immunosuppressive agents (cytostatic or biological) in the absence of lymphopenia and drug-induced parenchymal organ damage (liver, kidney).
7.AChEI dose stabilised = 4 weeks prior to randomisation (W1D1).
8. Electrophysiological test result of the myasthenia test (historical up to 5 years before the qualifying visit)or the test can be performed at the qualifying visit (W0).
9. MRI result of head with contrast (archived up to 5 years prior to qualifying visit or performed at qualifying visit).

DETAILED CRITERIA:
- the main cohort: validity of second-line immunoactive treatment indicated by failure to achieve pharmacological remission according to MGFA post-interventional status despite symptomatic acetylcholinesterase inhibitor treatment at optimal doses combined with chronic oral steroid therapy with achievement of stable 4 weeks prior to the randomisation visit (W1D1) prednisone equivalent dose.
- complementary cohort: no immunoactive treatment (acceptable symptomatic treatment with acetylcholinesterase inhibitors) and non-acceptance of the patient's side for the sick steroid therapy dictated by the disease before side effects.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Unusual distribution of muscle weakness or lack of apocamnosis effect with other diagnosis (such as LEMS, OPMD).
2. Negative results (below the cut-off threshold) of determinations of acetylcholine receptor auto-aggressive antibodies (anti-AChR-ab) or muscle tyrosine kinase (anti-MUSK-ab).
3. Electrophysiological exponents of presynaptic disorders of neuromuscular conduction (facilitation phenomenon in electromyographic myasthenia gravis test).
4. Coexistence of diseases that make it impossible to assess the disease state in the context of the severity of myasthenia gravis (e.g. cardiovascular or respiratory diseases clinically manifested by fatigue).
5. Coexistence of diseases that reduce resistance to opportunistic infection, which may be the cause of complications of immunoactive treatment of myasthenia gravis (e.g. HIV, hepatitis B or C, tuberculosis) or recurrent herpes zoster in treatment.
6. Tumour disease active at the time of the qualifying visit (W0) for the study, or completed non-deferred temporal
(< 6 months) oncological treatment.
7. Significant deviation in basic research:
- peripheral blood count: leukopenia < 1.5 x 109/l;
- neck functions: creatinine > 1.4 mg/dl in women and > 1.5 mg/dl in men;
- liver function: AST or ALT > 3x ggn;
- anti-IgA infection in people with IgA deficiency (in case emergency treatment is needed due to intravenous administration of human immunoglobulins *IVIG).
If there is improvement in follow-up, deviations from the above criteria are acceptable based on the patient's clinical presentation ( to be at the decision of the Investigator).
8. Hypersensitivity to cladribine or to any of them has been helpful:
- mechanical obstruction of the urinary tract (with attention to AChEI);
- pregnancy (patients of childbearing age will be required to declare use of an effective method of contraception [Pearl index =2 ] from the qualifying visit (W0) during the trial and 6 months after its completion);
- breastfeeding.
9. No use of an effective method of contraception [Pearl index = 2] by patients of childbearing age at the time of eligibility (visit W0) for the study until 6 months after the last dose of study medicinal product.
10. No use of barrier contraception by patients at the time of study eligibility (W0 visit) until 6 months after the last dose of study medicinal product.
11. Other contraindications which, in the opinion of the Investigator, exclude the patient from participating in the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified