Friedreich’s Ataxia MedDRA version: 20.0 Level: PT Classification code 10017374 Term: Friedreich's ataxia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Minoryx Therapeutics BE, SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent by the subject or parent/legal guardian, and/or consent or assent for minors as required by national laws. 2. Male and female subjects aged =12 and =60 years, inclusive, with Friedreich’s Ataxia confirmed by genetic testing. 3. Total score on SARA of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Age of onset of disease =25 years 2. Left ventricular ejection fraction (LVEF) 480 msec in 3 consecutive ECG recordings taken at least 5 minutes apart. 4. Known intolerance to pioglitazone or other thiazolidinediones. 5. Subjects who are taking or have taken pioglitazone, or other thiazolidinediones, within the past 6 months prior to Screening. 6. Currently participating in or having participated in another interventional clinical study within 2 months prior to Screening. 7. Requiring other prohibited concomitant medication (see Table 4). Note: use of idebenone, coenzyme Q10, antioxidants, riboflavin, thiamine, vitamins C and E is permitted provided the dose has been constant for =3 months before Screening and is kept constant during the entire study. 8. Previous or current history of vesical polyps, bladder cell hyperplasia, or bladder cancer. 9. Previous or current history of other cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years. 10. Subjects with clinically significant anemia (i.e. hemoglobin below 110 g/L). 11. Glycated hemoglobin (HbA1c) levels >6.4% and fasting blood glucose levels = 0.9 times the lower limit of normal and = 1.1 times the upper limit of normal. 12. NT-proB-type natriuretic peptide level (BNP) >125 pg/mL 13. Abnormal liver enzyme tests for aspartate aminotransferase or alanine aminotransferase of >2 times the upper limit of normal or total bilirubin >1.5 times the upper limit of normal (unless due to Gilbert’s syndrome). 14. A positive result on laboratory tests for hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antibody at screening. 15. Moderate or severe hepatic impairment (groups B and C according to the revised Child-Pugh classification; (Pugh, Murray-Lyon et al. 1973). 16. Chronic kidney disease (CKD) stages 3a or higher (according to CKD staging by Renal Association with an estimated glomerular filtration rate of <60 ml/min/1.73m2). 17. Contraindications for MRS/MRI procedure such as subjects with paramagnetic materials in the body, such as dental braces, spinal rods, aneurysm clips, pacemakers, intraocular metal or cochlear implants. 18. Drug or alcohol abuse in the past 2 years by subject history and/or investigator assessment. 19. Conditions which could modify the absorption of the study drug, such as inflammatory bowel diseases, or stomach or intestinal resection. 20. Inability or unwillingness of the subject or subjects’ parents/caregivers to comply with the study procedures. 21. Other medical, neurological, psychiatric, or social conditions that in the investigator’s opinion are likely to confound the assessment of safety or efficacy, interfere with study conduct, or unfavorably alter the risk-benefit of subject participation. 22. Pregnant women as confirmed by a positive blood pregnancy test. 23. Female patients intending to breast feed a child while taking study drug or have taken study drug within 30 days after administration of the last dose.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to evaluate the effect of 48 weeks of treatment with MIN-102 compared to placebo on cervical spinal cord area as assessed by morphometric MRI measurements. ;Secondary Objective: To evaluate the effect of 48 wks of treatment with MIN-102 compared to placebo on the following: -Change from baseline in the total score of the SARA -Cervical spinal cord mean, axial and radial diffusivity as assessed by MRI DTI -Cervical spinal cord tNAA/mIns ratio as assessed by MRS -Brain fiber density, fiber cross-section and fiber density and cross-section as assessed by fixel-based analyses -Cerebellar Composite Functional Scale, composed of 2 functional tests: 9 hole peg test and clicking -EQ-5D-5L -Fatigue Severity Scale -Activities of daily living (FARS) -Clinician and patient global impressions of improvement -Change in the pre-treatment versus post-treatment slope of the SARA (exploratory objective) -Neurophysiological parameters as assessed by motor evoked potentials (MEP). Optional assessment (exploratory objective) -Various biochemical parameters in plasma, and CSF. Optional assessment. (exploratory objective) -Safety and tolerability of MIN-102 ;Primary end point(s): Change from baseline in spinal cord area cervical segment C2-C3 [mm2] ;Timepoint(s) of evaluation of this end point: Baseline, week 24 and week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints include the change from baseline in: •Scale for Assessment and Rating of Ataxia: -Change from baseline in total score of the SARA •Diffusion tensor imaging fractional anisotropy: mean, radial and axial diffusivity cervical segments C2-C7 [10-3 mm2/s] •Magnetic resonance spectroscopy tNAA/mIns ratio in spinal cord segments C4-C5 •Fixel-based analyses of the brain including fiber density, fiber cross-section and FDC •Cerebellar Composite Functional Scale •EQ-5D-5L •Fatigue Severity Scale (FSS) •Activities of Daily Living subscale of FARS •Clinical Global Impressions – Severity (CGI-S) •Clinical Global Impressions – Improvement (CGI-I) •Patient Global Impressions – Improvement (PGI-I) Exploratory; •Clinical; Change in slope from baseline of the SARA compared from pre-treatment to post-treatment •Neurophysiological ( Motor evoked potentials with central conduction time and amplitude as an optional assessment) •Biochemical - Adiponectin in plasma, and CSF (optional) - Fatty acid binding protein 4 in CSF (optional) - Gene expression of frataxin, PGC-1a, NRF1, TFAM in peripheral blood mononuclear cells - Neurofilament light chain in plasma, and CSF (optional) Safety; •AEs, SAEs & SUSARs •vital signs •12-lead ECG •echocardiogram •clinical laboratory tests (included Pregnancy Screen) •Physical examination •palatability;Timepoint(s) of evaluation of this end point: - All; Baseline, week 24 and week 48 - CGI-I; Week 24 and week 48 - PGI-I; week 24 and week 48 - Safety: From screening, during the 48 weeks of treatment and 4 weeks after discontinuation - Palatability: Baseline, week 4, week 12, week 24 and week 36 | — |
Countries
Belgium, France, Germany, Spain
Contacts
Public ContactSílvia Pascual
Minoryx Therapeutics S.L.
Outcome results
None listed