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

NCT ID: NCT03917225

Last Updated: 2022-10-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-26
• Study Completion Date: 2020-09-14

Brief Summary

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

Detailed Description

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.

Conditions

Friedreich Ataxia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

MIN-102

MIN-102 (5-\[\[4-\[2-\[5-(1-Hydroxyethyl)-2-pyridinyl\]ethoxy\]phenyl\]methyl\]-2,4-thiazolidinedione hydrochloride (1:1)). Dosing is once daily at approximately the same time each morning throughout the entire treatment phase (48 weeks).

Group Type: EXPERIMENTAL

MIN-102

Intervention Type: DRUG

Once-daily dosing with a volume specified by the pharmacokinetic specialist to achieve the desired plasma exposure. MIN-102 oral suspension, strength 15 mg/ml.

Placebo

Matches MIN-102 visually and by taste. Dosing is once daily at approximately the same time each morning throughout the entire treatment phase (48 weeks).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Once-daily dosing with a volume specified by the pharmacokinetic specialist. Oral suspension.

Interventions

MIN-102

Once-daily dosing with a volume specified by the pharmacokinetic specialist to achieve the desired plasma exposure. MIN-102 oral suspension, strength 15 mg/ml.

Intervention Type: DRUG

Placebo

Once-daily dosing with a volume specified by the pharmacokinetic specialist. Oral suspension.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Minoryx Therapeutics, S.L.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandra Durr

Role: PRINCIPAL_INVESTIGATOR

ICM, Groupe Hospitalier Pitié Salpêtrière, Paris, France, 75646

Locations

Hôpital Erasme-ULB

Brussels, , Belgium

ICM, Groupe Hospitalier Pitié Salpêtrière

Paris, , France

Universitätsklinikum RWTH

Aachen, , Germany

Hospital Sant Joan de Déu

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Countries

Belgium; France; Germany; Spain

References

Pandolfo M, Reetz K, Darling A, Rodriguez de Rivera FJ, Henry PG, Joers J, Lenglet C, Adanyeguh I, Deelchand D, Mochel F, Pousset F, Pascual S, Van den Eede D, Martin-Ugarte I, Vila-Brau A, Mantilla A, Pascual M, Martinell M, Meya U, Durr A. Efficacy and Safety of Leriglitazone in Patients With Friedreich Ataxia: A Phase 2 Double-Blind, Randomized Controlled Trial (FRAMES). Neurol Genet. 2022 Nov 1;8(6):e200034. doi: 10.1212/NXG.0000000000200034. eCollection 2022 Dec.

Reference Type: DERIVED

PMID: 36524101 (View on PubMed)

Other Identifiers

MT-2-03

Identifier Type: -

Identifier Source: org_study_id