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Safety and Efficacy of Etravirine in Friedreich Ataxia Patients (FAEST1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04273165
Recruitment Status : Not yet recruiting
First Posted : February 17, 2020
Last Update Posted : May 7, 2020
Sponsor:
Collaborator:
University of Rome Tor Vergata
Information provided by (Responsible Party):
IRCCS Eugenio Medea

Brief Summary:
A drug repositioning effort provided evidence supporting the possible use of Etravirine, a drug approved for the treatment of HIV infections in patients starting from 2 years of age, as a treatment for FA. We found that Etravirine is able to increase Frataxin protein both in vitro - in cells derived from FA patients - and in vivo - in the heart and skeletal muscle of Frataxin-deficient YG8 mice. Because of these findings, and since Etravirine displays a generally favorable safety profile, we plan to launch an open-label, phase 2 clinical trial aimed at assessing the safety and efficacy of Etravirine in FA patients. We aim at recruiting 30 FA patients. 15 will be treated with Etravirine for 4 months at 200 mcg/day and 15 will be treated with Etravirine for 4 months at 400 mg/day. Efficacy primary endpoint will be represented changes in peak VO2 as measured by incremental cycle ergometer exercise test. Secondary endpoints will include maximal workload, SARA score, cardiac measures, Frataxin protein levels in peripheral blood mononuclear cells and molecular analysis of Frataxin mRNA translation efficiency. Complete sets of data will be collected 4 months before the start of the treatment (T -4), at the start (T0), after 2 months (T2), at the end of the treatment (T4) and 4 months after the termination of the treatment (T8).

Condition or disease Intervention/treatment Phase
Friedreich Ataxia Drug: Etravirine Tablets Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: dose comparison in open label pilot study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Clinical Trial to Test the Safety and Efficacy of Etravirine in Friedreich Ataxia Patients
Estimated Study Start Date : May 20, 2020
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : March 31, 2022


Arm Intervention/treatment
Active Comparator: Etravirine Dose 1
Etravirine dose 200 mg per diem(100+100)
Drug: Etravirine Tablets
Daily etravirine BID with 100 or 200 tablets for 4 months

Active Comparator: Etravirine Dose 2
Etravirine dose 400 mg per diem (200+200)
Drug: Etravirine Tablets
Daily etravirine BID with 100 or 200 tablets for 4 months




Primary Outcome Measures :
  1. Adverse event number and severity [ Time Frame: 4 months ]
    description and count of AE and SAE to document the safety of etravirine treatment at 200 mg/die and 400mg/die in FA patients


Secondary Outcome Measures :
  1. VO2 max increase [ Time Frame: 12 months ]
    efficacy of etravirine treatment in increasing aerobic capacity in FA patients comparing pre and post treatment periods


Other Outcome Measures:
  1. Scale for the Assessment and Rating of Ataxia [ Time Frame: 12 months ]
    Scale for the Assessment and Rating of Ataxia (SARA) score change comparing pre-, during- and post- treatment evaluations. SARA scores ataxia on a 0-40 points scale where 0 means no ataxia and 40 most severe ataxia

  2. Cardiac wall thickness (in mm) [ Time Frame: 12 months ]
    cardiac wall thickness (in mm) as measured by standard Echo cardiography

  3. Frataxin measurement [ Time Frame: 12 months ]
    Frataxin protein content in peripheral blood mononuclear cells

  4. short form 36 scale for quality of life [ Time Frame: 12 months ]
    changes in QoL as measured by the short form 36 (SF36) scale and disability as measured with the World Health Organization Disability Assessment schedule 2.0 (WHO-DAS 2.0) during the study period. Both tools are graded on a 0-100 scale where 100 is best and 0 is worst.



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Ages Eligible for Study:   10 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Molecularly defined FA diagnosis (at least one expanded FXN allele),
  • ability to complete maximal exercise testing (being able to ride a recumbent exercise ergometer at 60 rpm with no added resistance for at least 3 minutes),
  • willingness to participate, as shown by the signed consent form.

Exclusion Criteria:

  • Known intolerance to any of the components of the drug preparation.
  • Ongoing treatment with Etravirine or other experimental therapeutics under study for FA (e.g. IFNy, erythropoietin, nicotinamide, etc.).
  • Previous treatment, if any, should have been stopped at least 4 weeks before study entry.
  • Severe medical condition likely to interfere with drug absorbance and distribution (liver or kidney failure, severe metabolic unbalance), significant cardiac disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04273165


Contacts
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Contact: Andrea Martinuzzi, MD, PhD +3904384141 ext 296 andrea.martinuzzi@lanostrafamiglia.it
Contact: Gabriella Paparella, MD +3904389062 ext 330 ganriella.paparella@lanostrafamiglia.it

Sponsors and Collaborators
IRCCS Eugenio Medea
University of Rome Tor Vergata
Publications:
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Responsible Party: IRCCS Eugenio Medea
ClinicalTrials.gov Identifier: NCT04273165    
Other Study ID Numbers: 2019-002618-38
2019-002618-38 ( EudraCT Number )
First Posted: February 17, 2020    Key Record Dates
Last Update Posted: May 7, 2020
Last Verified: May 2020

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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:
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Ataxia
Cerebellar Ataxia
Friedreich Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinocerebellar Degenerations
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases
Etravirine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents