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

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

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

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: Artesunate Oral Product

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Centre d'Investigation Clinique, hôpital Necker Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Artesunate; 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; Dose escalation intake of artesunate

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: Imagine Institute
• Investigators: Principal Investigator: Arnold Munnich, MD, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Actual): April 17, 2024
• Study Completion (Actual): April 17, 2024

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Friedreich Ataxia; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate
• Other Study ID Numbers: C20-54; 2021-000171-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No