MT-2-03

Minoryx Therapeutics BE SA

Rue Auguste Piccard 48, 6041 Gosselies, Belgium,

Sílvia Pascual, Minoryx Therapeutics BE SA, 0034 935441466, spascual@minoryx.com

Sílvia Pascual, Minoryx Therapeutics BE SA, 0034 935441466, spascual@minoryx.com

No

No

No

Final

09 Oct 2020

No

Yes

14 Sep 2020

No

The main objective was to evaluate the effect of 48 weeks’ treatment with MIN-102 compared to placebo on cervical spinal cord area as assessed by morphometric MRI measurements. Secondary objectives and exploratory objectives were also evaluated. The secondary objectives included evaluating the effect of 48 weeks of treatment with MIN-102 compared to placebo on: change from baseline in the SARA (Scale for the Assessment and Rating of Ataxia) total score; diffusion tensor imaging (DTI) of the cervical spinal cord; cervical spinal cord total N-acetylaspartate concentration/myo-inositol (tNAA/Mins) ratio (using magnetic resonance spectroscopy [MRS]); MRI quantitative susceptibility mapping (QSM) for iron concentration; dentate nuclei volume; fixel-based analyses (FBA) of the brain; cerebellar composite functional scale (CCFS); fatigue severity scale (FSS); quality of life assessments; clinical and patient global impression of improvement; safety and tolerability of MIN-102.

All study patients (caregivers as applicable) were required to read and sign an Informed Consent Form; if the patient was a minor, investigators were required to obtain written informed consent from a parent/legal guardian and written assent from the patient. Consent/assent was obtained prior to any study-specific screening procedures. As part of this procedure, the investigator or an associate would explain orally and in writing the nature, duration, and purpose of the study and the action of the drug in such a manner that the patient/parent was aware of the potential risks, inconveniences, or adverse effects. The parent/legal guardian was informed that the patient could withdraw from the study at any time. In the event of a protocol modification, the Informed Consent Form was to be updated as applicable, with subsequent institutional review board (IRB)/independent ethics committee (IEC) approval and re-consenting of patients. For optional evaluations of motor evoked potentials and cerebrospinal fluid sampling, additional informed consent and assent was required, which was documented using a check box in the main consent form. In addition, optional consent was required for the collection of results from SARA assessments conducted prior to screening, in patients for whom these data were available. The decision of a patient to participate in these optional assessments or not had no impact on their inclusion in the study.

02 Apr 2019

No

Yes

Spain: 14

Belgium: 9

France: 9

Germany: 7

39

39

0

0

0

0

0

14

25

0

0

Overall trial (overall period)

Randomised - controlled

Patients were randomly assigned to MIN-102 or placebo in a 2:1 ratio using interactive response technology. Controls to maintain the double-blind status included: the oral suspensions containing active drug or placebo were indistinguishable in appearance and taste; the packaging and labeling of the bottles for both treatments was identical; dose adjustment (to achieve the target exposure) was managed by a central unblinded PK expert; random dose adjustments were made for placebo patients.

Yes

MIN-102

Leriglitazone hydrochloride

Oral suspension

Oral use

Patients received oral MIN-102 once daily for 48 weeks using a 10-mL syringe. Initial doses were 150 mg (adult males), 130 mg (adult females), and 2.2 mg/kg (patients ≥12 to 17 years). At Visit 1 (after 4 weeks of treatment) blood samples were collected for PK analysis; dosages for individuals were then modified by the PK specialist to achieve the desired plasma exposure of 170 µg.hr/mL in each patient. Patients received this dose throughout the study, unless reduction was necessary due to safety or tolerability. Administration could be temporarily interrupted if a patient experienced safety and/or tolerability issues or other conditions that prevented them taking study drug. Treatment was to be stopped if patients showed clinical signs of heart failure, left ventricular ejection fraction changes (drop to below 50% or an absolute drop of >10% from baseline), or if indicated after evaluating ECGs following elevations of NT-pro BNP (N-terminal pro B-type natriuretic peptide) >300 pg/mL.

Matching placebo

Oral suspension

Oral use

Patients received placebo once daily for 48 weeks using a 10-mL syringe. Random dose adjustments were made for patients receiving placebo in order to maintain the blind.

MIN-102 group

Placebo group

MIN-102 group

Placebo group

Values provided here are the least squares (LS) mean (standard error [SE]) change from Baseline to Week 48 area in measurements of spinal cord cervical segment C2-C3 area, estimated from the MRI T1-weighted brain image for the modified intent-to-treat (mITT) population. The mITT consisted of all patients who took at least 1 dose (partial or complete) of study drug and had at least 1 post-baseline spinal cord area cervical segment C2-C3 measurement and SARA assessment at the same visit. There was no conclusive outcome from the primary objective to evaluate the change from Baseline in cervical spinal cord area after 48 weeks of treatment. In both treatment groups, there was no clinically meaningful change in area from Baseline to Week 48; numerical differences between the groups (a small decrease in the area in the MIN-102 group [least squares (LS) mean change -0.394 mm²] and a small increase in the placebo group [0.076 mm²]) were not considered to be clinically relevant.

Primary

Baseline to Week 48

Placebo group v MIN-102 group

32

Pre-specified

This secondary efficacy endpoint evaluated the effect of 48 weeks of treatment with MIN-102 compared to placebo on magnetic resonance imaging (MRI) quantitative susceptibility mapping (QSM) for iron concentration. Values reported here are for the mITT population. At Baseline, the mean iron concentration was comparable in the MIT-102 and placebo groups (64.89 ppb and 73.86 ppb, respectively). The LS mean change from Baseline to 48 weeks saw little change in the MIN-102 group (increase of 0.098 ppb), with an increase of 4.858 ppb in the placebo group.

Secondary

Baseline to Week 48

Placebo group v MIN-102 group

26

Pre-specified

Treatment-emergent adverse events (TEAEs) were recorded from Baseline until the Follow-up Visit, which occurred 28 +/-5 days after the last dose of study drug.

TEAEs were defined as AEs occurring on or after the first dose of study treatment. Adverse events that were recorded more than twice in any group are reported here.

23.0

MIN-102 group

Placebo group