Evaluation of the Effect of Artesunate in Friedreich Ataxia (FA)

Study Overview
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Brief Summary
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This dose-escalation study is aimed at investigating a novel application for artesunate in the treatment of Friedreich ataxia. It will evaluate this novel application of oral artesunate using a surrogate biological marker as primary endpoint in a phase I-II open trial

Official Title
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Evaluation of the Effect of Artesunate in Friedreich Ataxia (FA) Phase I-II Efficacy-Toxicity of Artesunate in Friedreich Ataxia

Conditions
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Friedreich Ataxia

Intervention / Treatment
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* Drug: Artesunate Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with FA confirmed by genetic analysis Weight of at least 50 kg Compliant patient agreeing to come to all protocol visits Signature of consent form by patient or parents of minor patient Patients with no treatment during 30 days prior to the first intake of study drug, except cardiac, diabetes and spasticity treatments Patients agreeing to use effective contraception for the duration of the study and up to 91 days after the last dose of the study treatment Affiliation to an Health Insurance Scheme of beneficiary of such a scheme Exclusion Criteria: Patient under justice protection Female patients Abnormal biological values of renal and liver functions and cell blood count (CBC) Progressive associated disease Treatment interfering with iron transport within 30 days before first intake of artesunate Participation to another clinical trial Hypersensitivity to artesunate or to any component of the drug Blood potassium lower than normal value QT / QTc interval > 450 ms on the ECG performed at inclusion Congenital long QT syndrome Family history of sudden cardiac death before the age of 50 Heart disease: ischemia or myocardial infarction, congestive heart failure or conduction disorder in the 6 months preceding inclusion History of arrhythmia Electrolyte imbalances: hypomagnesemia, hypocalcemia Bradycardia (<50 beats per minute) Acute neurological events within 6 months prior to inclusion

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artesunate<br>Dose escalation of oral artesunate: Step 1: 25 mg daily (1 tablet) during one week Step 2: 50 mg daily (2 tablets) during one week (if no effect on biomarker and no adverse reaction at step 1) Step 3: 75 mg daily (3 tablets) during one week (if no effect on biomarker and no adverse reaction at step 2) Step 4: 100 mg daily (4 tablets) duing one week (if no efficacy and no adverse reaction at step 3) | Drug: Artesunate Oral Product<br>* Dose escalation intake of artesunate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Search for the maximal tolerated and effective dose of oral artesunate to regulate iron homeostasis and Transferrin 1 receptor (TfR1) immunofluorescence in Peripheral Blood Mononuclear Cells (PBMCs) | Evaluation of the biological efficacy on an ex vivo marker in the absence of observed side effects. This is a binary criterion established by comparison between compared measurements of the biomarker. If an effect on the biomarker is observed from the initial dose, the dose escalation will stop as the ex-vivo efficacy criterion is met. Otherwise the test will be repeated at an escalating dose. If an adverse effect is observed for a given dose, the maximal tolerated dose will be considered to be the immediately lower dose. | at Day 7 (last day of drug intake) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events with Artesunate in FA patients | Rate of side effects according artesunate doses | From first intake to 30 days after last intake of study drug | 
| Type of Adverse Events with Artesunate in FA patients | Desciption of side effects according artesunate doses | From first intake to 30 days after last intake of study drug | 
| Impact of stopping an effective dose of artesunate on the regulation of iron homeostasis and TfR1 immunofluorescence | 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 PBMCs obtained with the sample at the end of the week without treatment with those obtained at the end of the week under treatment at a given dose | At Day 14 (7 days after the last drug intake) |