Safety and Efficacy of Etravirine in Friedreich Ataxia Patients

NCT04273165 | Completed Phase 2 DMC

• 1 other identifier: 2019-002618-38
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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).

Conditions

Friedreich Ataxia

Outcome Measures

Primary Outcomes (1)

• Adverse event number and severity

  description and count of AE and SAE to document the safety of etravirine treatment at 200 mg/die and 400mg/die in FA patients

  4 months

Secondary Outcomes (1)

• VO2 max increase

  12 months

Other Outcomes (4)

• Scale for the Assessment and Rating of Ataxia

  12 months

• Cardiac wall thickness (in mm)

  12 months

• Frataxin measurement

  12 months

Study Arms (2)

Etravirine Dose 1

ACTIVE COMPARATOR

Etravirine dose 200 mg per diem(100+100)

Drug: Etravirine Tablets

Etravirine Dose 2

ACTIVE COMPARATOR

Etravirine dose 400 mg per diem (200+200)

Drug: Etravirine Tablets

Interventions

Etravirine Tablets DRUG

Daily etravirine BID with 100 or 200 tablets for 4 months

Etravirine Dose 1; Etravirine Dose 2

Eligibility Criteria

• Age: 10 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• IRCCS Eugenio Medea: lead
• University of Rome Tor Vergata: collaborator

Study Sites (1)

IRCCS Medea Scientific Institute, Pieve di Soligo Research Centre

Pieve di Soligo, TV, 31953, Italy

Location

Related Publications (2)

• Paparella G, Straga C, Pesenti N, Dal Molin V, Martorel GA, Merotto V, Genova C, Piazza A, Piccoli G, Panzeri E, Rufini A, Testi R, Martinuzzi A. A Pilot Phase 2 Randomized Trial to Evaluate the Safety and Potential Efficacy of Etravirine in Friedreich Ataxia Patients. Children (Basel). 2024 Aug 9;11(8):958. doi: 10.3390/children11080958.

  PMID: 39201893 BACKGROUND

• Alfedi G, Luffarelli R, Condo I, Pedini G, Mannucci L, Massaro DS, Benini M, Toschi N, Alaimo G, Panarello L, Pacini L, Fortuni S, Serio D, Malisan F, Testi R, Rufini A. Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia. Mov Disord. 2019 Mar;34(3):323-334. doi: 10.1002/mds.27604. Epub 2019 Jan 9.

  PMID: 30624801 BACKGROUND

MeSH Terms

Conditions

Friedreich Ataxia

Interventions

etravirine

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: dose comparison in open label pilot study

Study Record Dates

• First Submitted: February 14, 2020
• First Posted: February 17, 2020
• Study Start: September 17, 2020
• Primary Completion: January 17, 2023
• Study Completion: January 17, 2023
• Last Updated: December 4, 2024

Record last verified: 2024-11

Locations

IT (1)