CLADRIBINE for Myasthenia gravis|Seropositive myasthenia gravis

Inclusion criteria

• {"criterion_text":"- Age > 18 years (no border).\n- 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.\n- DETAILED CRITERIA - complementary cohort: no immunoactive treatment (acceptable symptomatic treatment with acetylcholinesterase inhibitors) and nonacceptance of the patient's side for the sick steroid therapy dictated by the disease before side effects.\n- Obtaining informed consent for the patient's participation in the entry.\n- The characteristic clinical picture of myasthenia gravis with nonpainful movement of typical striated muscle groups with the intensity of professional development changing throughout the day.\n- 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).\n- 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.\n- 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).\n- AChEI dose stabilised ≥ 4 weeks prior to randomisation (W1D1).\n- 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).\n- MRI result of head with contrast (archived up to 5 years prior to qualifying visit or performed at qualifying visit)."}

Exclusion criteria

• {"criterion_text":"- Unusual distribution of muscle weakness or lack of apocamnosis effect with other diagnosis (such as LEMS, OPMD).\n- 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.\n- Other contraindications which, in the opinion of the Investigator, exclude the patient from participating in the study.\n- 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).\n- Electrophysiological exponents of presynaptic disorders of neuromuscular conduction (facilitation phenomenon in electromyographic myasthenia gravis test).\n- 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).\n- 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.\n- Tumour disease active at the time of the qualifying visit (W0) for the study, or completed non-deferred temporal (< 6 months) oncological treatment.\n- 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).\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Changes in the evaluation of the effects of intensified myasthenia symptoms on the daily living activities according to the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale during visits assessing efficacy: W2 – W8 during the basic examination time and W10 – W15 during additional testing time, comparing to the baseline result (W1 in the basic study period and W9 in the additional study time).","definition_or_measurement_approach":"Measured as change in MG-ADL (Myasthenia Gravis Activities of Daily Living) score versus baseline (W1 for basic period; W9 for additional period). Assessed at visits W2–W8 (basic) and W10–W15 (additional) compared to baseline."}

Secondary endpoints

• {"endpoint_text":"- Reduction in the requirement for simultaneous oral corticosteroids used in immunotherapy (steroid-sparing effect). The endpoint will only be assessed in the core cohort. Assessment for W4-W8 during the basic duration of the study and W12-W15 during the additional duration of the study.","definition_or_measurement_approach":"Assessed as reduction in oral corticosteroid requirement in core cohort at visits W4–W8 (basic) and W12–W15 (additional)."}
• {"endpoint_text":"- Incidence of the need for rescue therapy due to exacerbation of myasthenia gravis with respiratory failure at any time during the study period, separately in the primary and secondary study periods.","definition_or_measurement_approach":"Measured as occurrence (incidence) of rescue therapy for respiratory failure at any time during primary and secondary study periods."}
• {"endpoint_text":"- Change in antibodies against acetylcholine receptors (anti-AChR-ab) and specific muscle tyrosine kinase (anti-MUSK-ab) in blood serum compared to the baseline result (on W1 during the basic study period and on W9 during the additional study period). Score for W3 and W6 during the basic study period and W11 and W15 during the additional study period.","definition_or_measurement_approach":"Measured change in serum anti-AChR and anti-MUSK antibody levels versus baseline; assessed at W3 and W6 (basic) and W11 and W15 (additional)."}
• {"endpoint_text":"- Change in the concentration of complement system components (C3, C4) compared to the baseline result (on W1 during the basic test period and on W9 during the additional test period). Score for W3 and W6 during the basic study period and W11 and W15 during the additional study period.","definition_or_measurement_approach":"Measured change in serum C3 and C4 concentrations versus baseline; assessed at W3 and W6 (basic) and W11 and W15 (additional)."}
• {"endpoint_text":"- Change in cytokine concentration relative to the baseline result (on W1 during the basic study period and on W9 during the additional study period). Score for W3 and W6 during the basic study period and W11 and W15 during the additional study period.","definition_or_measurement_approach":"Measured change in cytokine concentrations in serum versus baseline; assessed at W3 and W6 (basic) and W11 and W15 (additional)."}
• {"endpoint_text":"- Change in the percentage of individual lymphocyte populations in lymphocyte immunophenotyping compared to the baseline result (on W1 during the basic study period and on W9 during the additional study period). Score for W3 and W6 during the basic study period and W11 and W15 during the additional study period.","definition_or_measurement_approach":"Measured change in percentages of lymphocyte subpopulations by immunophenotyping versus baseline; assessed at W3 and W6 (basic) and W11 and W15 (additional)."}
• {"endpoint_text":"- Frequency of adverse events.","definition_or_measurement_approach":"Measured as incidence/frequency counts of adverse events reported during the study."}
• {"endpoint_text":"- Change in safety parameters (blood count, creatinine, urea, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGTP), C-reactive protein (CRP), procalcitonin PCT, urinalysis) compared to the baseline result (on W1 during the basic test period and on W9 during the additional test period). Assessment for W3-W8 during the basic study period and W11-W15 during the additional study period.","definition_or_measurement_approach":"Measured changes in listed lab safety parameters versus baseline; assessed at W3–W8 (basic) and W11–W15 (additional)."}
• {"endpoint_text":"- Assessment of cladribine pharmacokinetics in plasma at visits W1 (on days D1, D3 and D4) and W2.","definition_or_measurement_approach":"Plasma pharmacokinetic assessment of cladribine measured on W1 (days D1, D3, D4) and W2."}

Methods

• Recruitment arrangements and materials documented (K1_Recruitment arrangements) — specific channels not detailed in JSON.
• Study information poster (K2_Recruitment material_Study Information Poster).
• Study information film (K2_Recruitment material_Study Information Film Script).
• Study information brochure (K2_Recruitment material_Study Information Brochure).

Poland

Earliest CTIS Part Ii Submission Date

09-08-2024

Latest Decision Or Authorization Date

30-11-2025

Processing Time Days

478

Number Of Sites

6

Number Of Participants

200

Primary sponsor

Full Name

Uniwersytet Medyczny W Lublinie

Organisation Type

Educational Institution

Country Of Registered Address

Poland

Contract research organisations

Name

Scientia Research Institute Sp. z o.o.

Responsibilities

Operational/study support roles referenced by sponsorDuties codes 1,10,12,14,5,6,7,8,9 (specific mappings not provided in JSON)

Third parties

• {"country":"Poland","full_name":"Uniwersytet Medyczny W Lublinie","duties_or_roles":"Phenotyping of cells of the immune system","organisation_type":"Educational Institution"}
• {"country":"Poland","full_name":"Instytut Psychiatrii I Neurologii","duties_or_roles":"Testing immunological tests - determinations anti-AchR and anti-Musk antibodies","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Cefea Sp. z o.o. S.K.","duties_or_roles":"Code 14 (role not further specified in JSON)","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Siec Badawcza Lukasiewicz Instytut Chemii Przemyslowej Imienia Profesora Ignacego Moscickiego","duties_or_roles":"Analysis of plasma cladribine concentrations in the assessment of pharmacokinetics; other duties codes: 14,4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Mossakowski Medical Research Centre Polish Academy Of Sciences","duties_or_roles":"Conducting biochemical tests - determination of cytokine/chemokine profile in blood serum; other duties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Scientia Research Institute Sp. z o.o.","duties_or_roles":"Multiple operational roles referenced by codes: 1,10,12,14,5,6,7,8,9 (detailed responsibilities not expanded in JSON)","organisation_type":"Pharmaceutical company"}