A Clinical Study to Evaluate the Effect of MIN-102 on the Progression of Friedreich's Ataxia in Male and Female Patients

Randomized, double-blind, placebo-controlled study on the effects of MIN-102 on Biochemical, Imaging, neurophysiological, and clinical markers in patients with Friedreich's Ataxia

This study investigated whether treatment with MIN-102 was able to influence clinical, neurophysiological, and imaging parameters, as well as various peripheral and central nervous system biochemical markers related to mitochondrial dysfunction, in patients with Friedreich's ataxia (FRDA), over a period of 48 weeks in a double-blind, placebo-controlled design.

Patients were screened following written consent (and assent if the patient was a minor) at the Screening visit (V-1). Eligible patients attended a Baseline visit (V0) within a maximum of 28 days after V-1 and were randomized in a 2:1 ratio to receive an individualized starting dose of MIN-102 or placebo, which they took daily for 48 weeks. Patients received individualized starting doses based on gender and age, which were subsequently modified based on pharmacokinetic (PK) parameters obtained from blood samples at V1 to achieve a target MIN-102 exposure of 170 μg.hr/mL.

In addition to the Screening visit (V-1) and Baseline visit (V0), patients were evaluated at 2 interim safety visits (ISV) occurring 2 and 8 weeks after V0 (ISV1 and ISV2; permitted to be home visits performed by a Good Clinical Practice \[GCP\]-certified nurse), and at 4 weeks (V1), 12 weeks (V2), 24 weeks (V3), 36 weeks (V4), and 48 weeks (V5) after V0.

Results of all scheduled assessments were made available to the investigator as soon as possible. Patients received regularly scheduled phone calls at 6, 10, 16, 20, 28, 32, 40, and 44 weeks after V0 to review changes in concomitant medications and adverse events (AEs), particularly for symptoms possibly indicative of cardiac failure. A Final Follow-up Visit (FUV) took place 4 weeks after the last dose of study drug.

Evaluations consisted of imaging evaluations at V0, V3, and V5, evaluations of clinical status using the Scale for the Assessment and Rating of Ataxia (SARA), cerebellar composite functional scale (CCFS), global clinical rating scales, and patient questionnaires at V0, V3, and V5, assessment of biochemical markers in plasma at V0, V2, V3, and V5, and blood sampling for plasma levels of MIN-102 and its main metabolite (M3) at all scheduled on-site visits (except for ISV1 and ISV2). Assessments for safety and tolerability included collection of AEs, as well as electrocardiograms (ECGs), echocardiograms, and laboratory tests. Palatability was assessed at V0, V1, V2, V3, and V4. Measurements of motor evoked potentials (MEPs) and assessment of biochemical markers in cerebrospinal fluid (CSF) were optional evaluations at V0, V3, and V5. All assessments for safety, tolerability, and biochemical markers in plasma were also performed at premature discontinuation.

Eligibility Criteria:
Inclusion Criteria:

* Male and female subjects aged ≥12 and ≤60 years, inclusive, with a genetically confirmed diagnosis of Friedreich's Ataxia.
* Be able to walk \>10 meters with support (two special sticks, stroller, or accompanying person).
* Total score on the Scale for the Assessment and Rating of Ataxia (SARA) of \<25.

Exclusion Criteria:

* Age of onset of disease ≥25 years.
* Higher degree of cardiomyopathy assessed by echocardiogram.
* Diabetes.