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

Primary Purpose

Friedreich Ataxia

Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Artesunate Oral Product
Sponsored by
Institut National de la Santé Et de la Recherche Médicale, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Friedreich Ataxia

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Centre d'Investigation Clinique, hôpital Necker Enfants MaladesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Artesunate

Arm Description

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Incidence of Adverse Events with Artesunate in FA patients
Rate of side effects according artesunate doses
Type of Adverse Events with Artesunate in FA patients
Desciption of side effects according artesunate doses
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

Full Information

First Posted
May 31, 2021
Last Updated
July 11, 2023
Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborators
Imagine Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04921930
Brief Title
Evaluation of the Effect of Artesunate in Friedreich Ataxia (FA)
Acronym
ARTEMIS
Official Title
Evaluation of the Effect of Artesunate in Friedreich Ataxia (FA) Phase I-II Efficacy-Toxicity of Artesunate in Friedreich Ataxia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 6, 2022 (Actual)
Primary Completion Date
December 5, 2023 (Anticipated)
Study Completion Date
December 5, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborators
Imagine Institute

4. Oversight

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
Data Monitoring Committee
Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich Ataxia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Artesunate
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Artesunate Oral Product
Intervention Description
Dose escalation intake of artesunate
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
at Day 7 (last day of drug intake)
Secondary Outcome Measure Information:
Title
Incidence of Adverse Events with Artesunate in FA patients
Description
Rate of side effects according artesunate doses
Time Frame
From first intake to 30 days after last intake of study drug
Title
Type of Adverse Events with Artesunate in FA patients
Description
Desciption of side effects according artesunate doses
Time Frame
From first intake to 30 days after last intake of study drug
Title
Impact of stopping an effective dose of artesunate on the regulation of iron homeostasis and TfR1 immunofluorescence
Description
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
Time Frame
At Day 14 (7 days after the last drug intake)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Arnold Munich
Phone
+33142754200
Email
arnold.munnich@inserm.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arnold Munnich, MD
Organizational Affiliation
Institut National de la Santé Et de la Recherche Médicale, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre d'Investigation Clinique, hôpital Necker Enfants Malades
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arnold Munnich

12. IPD Sharing Statement

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

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