Friedreich Ataxia
Conditions
Brief summary
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
Interventions
DRUGArtesunate Oral Product
Dose escalation intake of artesunate
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Imagine Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
16 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | at Day 7 (last day of drug intake) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events with Artesunate in FA patients | From first intake to 30 days after last intake of study drug | Rate of side effects according artesunate doses |
| Type of Adverse Events with Artesunate in FA patients | From first intake to 30 days after last intake of study drug | Desciption of side effects according artesunate doses |
| Impact of stopping an effective dose of artesunate on the regulation of iron homeostasis and TfR1 immunofluorescence | At Day 14 (7 days after the last drug intake) | 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 |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORArnold Munnich, MD
Institut National de la Santé Et de la Recherche Médicale, France
Outcome results
None listed