Friedreich Ataxia MedDRA version: 20.0 Level: PT Classification code 10017374 Term: Friedreich's ataxia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: artesunate
Pharmaceutical Form: Tablet
Sponsors
INSERM
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Patients with FA confirmed by genetic analysis Male patients aged minimum 16 and maximum 65 Weight = 50 kg Compliant patients agreeing to come to all protocol visits Signature of consent form by patient or by parents of minor patient Patients who have taken no treatment within 30 days prior to first artesunate intake, apart from cardiac treatments (antithrombotics, anticoagulants, antihypertensive drugs, ß-blockers) Affiliation to a social security scheme Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Individuals placed under judicial protection Female patients Abnormal values ??of renal function (creatinine, creatinine clearance, etc.), hepatic function (transaminases, bilirubin, etc.), CBC (red blood cells, leucocytes, platelets, etc.) Associated progressive disease (cancer, hepatitis, etc.) Treatment interfering with iron transport within 30 days before the first dose of artesunate Participation in another therapeutic trial Hypersensitivity to artesunate or to any component of the drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Search for the maximum tolerated and effective dose of oral artesunate (tablet of 25 mg) to regulate iron homeostasis and TfR1 immunofluorescence in PBMC;Secondary Objective: Safety of artesunate in FA patients Impact of stopping the intake of an effective dose of artesunate on the regulation of iron homeostasis and TfR1 immunofluorescence;Primary end point(s): The primary endpoint evaluates the biological efficacy on an ex vivo marker in the absence of observed side effects. This is a binary endpoint established by comparison between compared measurements on blood samples taken before / after exposure of the subject to a 7-day intake of a given dose of the study product (artesunate). The effective dose of oral artesunate will be searched by detecting the biomarker (total cellular iron content) tested ex vivo in PBMC obtained by a simple blood test on EDTA. Each subject entering the study has a blood sample at time 0, a sample at the end of week 1 under treatment (level 1), then at the end of week 2 without treatment. Each cycle is repeated at increasing dose levels in the absence of side effect (steps 2, 3 and 4), and this as long as no reaction is observed on the in vitro test. A comparative evaluation of the slope of the regression of the intracellular iron concentration as a function of time will be calculated for each reached level: at D0 and D7 for level 1, at D14 and D21 for level 2, at D28 and D35 for level 3 and at D42 and D49 for level 4. A slope below 0.075 (or a division by 3 of the slope) will be considered as demonstrating a positive effect of the study product. If an effect is observed from the first dose used, the dose escalation will be stopped as an "ex vivo" efficacy on the primary endpoint selected will be observed. Otherwise, the test will be repeated for each dose. If an adverse effect, serious or not serious, for a voluntary patient is observed for a given dose, the maximum tolerated dose for this patient will be considered to | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Rate and description of adverse event dependng on administered doses of artesunate. Evolution of the response to treatment after one week without treatment in patients who presented a positive response: Comparison of the results of intracellular iron concentration in in vitro PBMC obtained with the sample at the end of the week without treatment with those obtained at the end of the week under treatment (D14 versus D7, D28 versus D21, D42 versus D35 and D56 versus D49).;Timepoint(s) of evaluation of this end point: Rate and description of adverse event fo: Throughout the study Evolution of the response to treatment after one week without treatment in patients who presented a positive response: at D14 for level 1, D28 for level 2, D42 for level 3 and D56 for level 4 | — |
Countries
France
Contacts
Public ContactHélène Espérou
INSERM
Outcome results
None listed