Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Pilot Phase 2 Randomized Trial to Evaluate the Safety and Potential Efficacy of Etravirine in Friedreich Ataxia Patients

Gabriella Paparella
ORCID logo ,
Cristina Stragà
,
Nicola Pesenti
,
Valentina Dal Molin
,
Gian Antonio Martorel
,
Vasco Merotto
,
Cristina Genova
,
Arianna Piazza
,
Giuseppe Piccoli
,
Elena Panzeri
ORCID logo ,
Alessandra Rufini
ORCID logo ,
Roberto Testi
,
Andrea Martinuzzi
* ORCID logo
Version 1 : Received: 21 February 2024 / Approved: 22 February 2024 / Online: 23 February 2024 (08:29:52 CET)

How to cite: Paparella, G.; Stragà, C.; Pesenti, N.; Dal Molin, V.; Martorel, G.A.; 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. Preprints 2024, 2024021303. https://doi.org/10.20944/preprints202402.1303.v1 Paparella, G.; Stragà, C.; Pesenti, N.; Dal Molin, V.; Martorel, G.A.; 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. Preprints 2024, 2024021303. https://doi.org/10.20944/preprints202402.1303.v1

Abstract

A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a treatment for Friedreich Ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted this pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Thirty-five patients were stratified into 3 severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T-4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T+4). Etravirine was well tolerated. Etravirine completely stopped the progression of the SARA score during the 4-months treatment period, compared to the 4 months pre and post treatment. It increased peak workload, while the improvement of peak oxygen uptake was not statistically significant. No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. In this open trial etravirine significantly improved neurological function and was generally safe and reasonably tolerated. This suggests that etravirine represents a potential therapeutic agent in FRDA deserving testing in a randomized placebo controlled clinical trial.

Keywords

Friedreich ataxia; etravirine; treatment; safety; efficacy

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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