Clinical trial NCT03917225: A Clinical Study to Evaluate the Effect of MIN-102 on the Progression of Friedreich's Ataxia in Male and Female Patients
Official title: A Double-Blind, Placebo-controlled Study on the Effects of MIN-102 on Biochemical, Imaging, Neurophysiological, and Clinical Markers in Patients With Friedreich's Ataxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Friedreich Ataxia
Keywords: Leriglitazone
Friedreich's ataxia
Lead sponsor: Minoryx Therapeutics, S.L.
Sponsor class: INDUSTRY
First posted: 2019-04-17
Enrollment: 39
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change from Baseline in spinal cord area cervical segment C2-C3 [mm²]
timeFrame: Baseline to 48 weeks
Secondary outcomes:
measure: Change from Baseline in SARA total score at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in cervical spinal cord (C2-C7) in fractional anisotropy at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in cervical spinal cord (C2-C7) in mean, axial, and radial diffusivity (10-³ mm²/s) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in spinal cord total N-acetylaspartate concentration/myo-inositol (tNAA/mIns) ratio as assessed by magnetic resonance spectroscopy (MRS) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in quantitative susceptibility mapping (QSM) for iron concentration (ppb) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in dentate nuclei volume at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in fixel-based analysis (FBA) of the brain at Week 48: fiber density (FD)
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in fixel-based analysis (FBA) of the brain at Week 48: fiber cross-section (FC)
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in fixel-based analysis (FBA) of the brain at Week 48: fiber density and cross-section (FDC)
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in Cerebellar Composite Functional Scale (CCFS) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in quality of life as measured by European Quality of Life 5 Dimensions (EQ-5D-5L) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in fatigue severity scale (FSS) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in Activities of Daily Living subscale of Friedreich's Ataxia Rating Scale (FARS) at Week 48
timeFrame: Baseline to 48 weeks
measure: Change from Baseline in Clinician Global Impression of Severity (CGI-S) at Week 48
timeFrame: Baseline to 48 weeks
measure: Assessment from Baseline in Clinician Global Impression of Improvement (CGI-I) at Week 48
timeFrame: 24 weeks and 48 weeks
measure: Assessment from Baseline in Patient Global Impression of Improvement (PGI-I) at Week 48
timeFrame: 24 weeks and 48 weeks
measure: Percentage of patients responding to palatability of study drug questions
timeFrame: Baseline, Week 4, Week 12, Week 24, and Week 36
measure: Frequency and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: Baseline to Final Follow-up Visit (approximately 52 weeks)
measure: Vital signs: percentage change from Baseline in body weight (kg)
timeFrame: Baseline to Final Follow-up Visit (approximately 52 weeks)
measure: Vital signs: change from Baseline in blood pressure (mmHg)
timeFrame: Baseline to Final Follow-up Visit (approximately 52 weeks)
measure: Vital signs: change from Baseline in pulse rate (beats/min)
timeFrame: Baseline to Final Follow-up Visit (approximately 52 weeks)
measure: Vital signs: change from Baseline in body temperature (°C)
timeFrame: Baseline to Final Follow-up Visit (approximately 52 weeks)
measure: Number of patients with abnormal, clinically significant electrocardiogram (ECG) and echocardiogram interpretations
timeFrame: Baseline to Final Follow-up Visit (approximately 52 weeks)
measure: Number of patients with abnormal, clinically significant physical examination findings
timeFrame: Screening to Final Follow-up Visit (approximately 56 weeks)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hôpital Erasme-ULB
city: Paris
country: France
facility: ICM, Groupe Hospitalier Pitié Salpêtrière
city: Aachen
country: Germany
facility: Universitätsklinikum RWTH
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: ICM, Groupe Hospitalier Pitié Salpêtrière, Paris, France, 75646
name: Alexandra Durr
role: PRINCIPAL_INVESTIGATOR
References: