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

Friedreich Ataxia Clinical Trial

— ARTEMIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04921930
• Other study ID #: C20-54
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 6, 2022
• Est. completion date: December 5, 2023

Study information

• Verified date: June 2023
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Arnold Munich
• Phone: +33142754200
• Email: arnold.munnich[@]inserm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 5, 2023
• Est. primary completion date: December 5, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Friedreich Ataxia

Intervention

Drug:
• Artesunate Oral Product
Dose escalation intake of artesunate

Locations

Country	Name	City	State
France	Centre d'Investigation Clinique, hôpital Necker Enfants Malades	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France	Imagine Institute

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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)