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

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04921930
• Collaborator: Imagine Institute (Other)
• Enrollment: 20
• Arm: 1
• Anticipated Duration (Months): 12

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Friedreich Ataxia	Drug: Artesunate Oral Product	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Effect of Artesunate in Friedreich Ataxia (FA) Phase I-II Efficacy-Toxicity of Artesunate in Friedreich Ataxia
• Anticipated Study Start Date: Jul 1, 2021
• Anticipated Primary Completion Date: Jun 30, 2022
• Anticipated Study Completion Date: Jun 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France
• Imagine Institute

Investigators

• Principal Investigator: Arnold Munnich, MD, Institut National de la Santé Et de la Recherche Médicale, France

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
• ClinicalTrials.gov Identifier: NCT04921930
• Other Study ID Numbers: C20-54
• First Posted: Jun 10, 2021
• Last Update Posted: Jun 14, 2021
• Last Verified: Jun 1, 2021

• 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
• Additional relevant MeSH terms: Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Artesunate

Study Results

No Results Posted as of Jun 14, 2021