Long-Term Open-Label Evaluation of Vatiquinone Safety and Efficacy in Friedreich Ataxia Patients Previously Exposed to Vatiquinone

The primary objective of this study is to assess the long-term **safety** of vatiquinone in patients with **Friedreich ataxia** (FA) who have been previously exposed to the drug. Evaluating the safety profile of vatiquinone over an extended period is clinically significant as it provides essential data on the tolerability and potential adverse effects of the treatment, which is crucial for its continued use in managing FA.

Secondary objectives include:

• Assessing the effects of vatiquinone on the Modified Friedreich Ataxia Rating Scale (mFARS) and its subscales in subjects with FA who were previously exposed to vatiquinone in prior studies (PTC743NEU-003-FA or PTC743-NEU-005-FA). This evaluation is important for understanding the impact of vatiquinone on disease progression and symptom management in FA patients.

The clinical trial involves a total of **100 participants** diagnosed with **Friedreich ataxia**. The study population includes both male and female subjects, with an age range encompassing children, adolescents, and adults. Participants were selected based on their completion and direct rollover from a previous vatiquinone clinical study. The trial does not include a vulnerable population. Participants are required to adhere to specific lifestyle considerations, such as the use of effective contraception methods for those of childbearing potential, and male participants must agree not to donate sperm during the study and for a specified period afterward. The general health status of participants is not specified beyond their diagnosis and previous exposure to vatiquinone.

The clinical trial is designed to evaluate the long-term safety and efficacy of **vatiquinone** in patients with **Friedreich ataxia**. This study is an open-label, Phase III trial, where participants who have previously been exposed to vatiquinone in earlier studies will be enrolled. The trial will involve the administration of vatiquinone as an oral solution, with a maximum daily dose of 200 mg and a total dose not exceeding 1200 mg over a treatment period of up to 36 months. The primary endpoint focuses on monitoring adverse events, serious adverse events, laboratory abnormalities, vital signs, and electrocardiograms. Secondary endpoints include changes from baseline in the modified Friedreich's Ataxia Rating Scale (mFARS) and its subscales.

Participants will be required to attend several study visits throughout the trial. The initial visit will serve as a screening to confirm eligibility, which includes criteria such as completion of a previous vatiquinone study and agreement to use effective contraception. Follow-up visits will be scheduled periodically to assess safety and efficacy parameters, with the final visit marking the end of the study. The estimated duration of participant involvement is approximately five years, from the recruitment start date in December 2022 to the estimated end date in December 2027. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or withdrawal of consent by the participant.

The clinical trial involves the administration of **Vatiquinone**, an experimental medication developed by PTC Therapeutics, Inc. Vatiquinone is presented in the form of an **oral solution** and is identified by the sponsor product code PTC743. The active substance, Vatiquinone, is of chemical origin and is being investigated for its potential therapeutic effects in patients with Friedreich Ataxia, a type of mitochondrial disease. The medication is administered orally, with a maximum daily dose of 200 mg and a total maximum dose of 1200 mg over the course of the treatment. The maximum treatment period is 36 months. The study aims to assess the long-term safety and efficacy of Vatiquinone in patients who have previously been exposed to the drug.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of Vatiquinone. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed to provide comprehensive data on the safety profile of Vatiquinone over an extended period, contributing to the understanding of its potential as a treatment for Friedreich Ataxia.

The efficacy of Vatiquinone in patients with **Friedreich Ataxia** will be assessed through secondary endpoints, which include the change from baseline in the modified Friedreich's Ataxia Rating Scale (mFARS) and its four subscales: Upright Stability, Upper Limb, Lower Limb, and Bulbar. These assessments will provide a comprehensive evaluation of the drug's impact on the various functional domains affected by the disease. The mFARS is a validated scale commonly used in clinical trials for Friedreich Ataxia to quantify disease progression and treatment effects.