Clinical Trials Register

Summary
EudraCT Number:	2018-004405-64
Sponsor's Protocol Code Number:	MT-2-03
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-12-14
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2018-004405-64

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study comparing the effect of MIN-102 and an inactive substance to learn more about the effects of the MIN-102 on Biochemical, Imaging, Neurophysiological, and Clinical Markers in Patients with Friedreich’s Ataxia, in which neither investigators nor subjects know what treatment the subject is receiving.

A.4.1

Sponsor's protocol code number

MT-2-03

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Minoryx Therapeutics BE, SA
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Minoryx Therapeutics S.L.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Minoryx Therapeutics S.L.
B.5.2	Functional name of contact point	Sílvia Pascual
B.5.3	Address:
B.5.3.1	Street Address	Av. Ernest Lluch 32, TCM3
B.5.3.2	Town/ city	Mataró (Barcelona)
B.5.3.3	Post code	08302
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034935441466
B.5.5	Fax number	0034930160119
B.5.6	E-mail	spascual@minoryx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	5-[[4-[2-[5-(1-Hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione hydrochloride
D.3.2	Product code	MIN-102
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	5-[[4-[2-[5-(1-Hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione hydrochloride
D.3.9.1	CAS number	146062-46-6
D.3.9.2	Current sponsor code	MIN-102
D.3.9.3	Other descriptive name	Hydroxypioglitazone hydrochloride
D.3.9.4	EV Substance Code	SUB16466MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral suspension
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Friedreich’s Ataxia

E.1.1.1

Medical condition in easily understood language

Friedreich’s Ataxia

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10017374
E.1.2	Term	Friedreich's ataxia
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal 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 <25.
4. Score on SARA item 1 (gait) ≥2 and ≤6.
5. Male with a potentially fertile partner must be willing to use an acceptable method of contraception for the duration of the study and for 3 months after study drug discontinuation (acceptable methods are: use of a condom with spermicide or use of oral, implantable or injectable contraceptives, or intrauterine devices, or a diaphragm with spermicide or diaphragm with condom) or have had a vasectomy.
6. Female with childbearing potential must be willing to use highly effective contraceptive methods during screening, during the period of drug administration and for 30 days after stopping study drug administration. Highly effective contraception methods include the following:
▪ Total abstinence (defined as refraining from heterosexual intercourse during the entire period outlined above).
▪ Male or female sterilization. (bilateral tubal occlusion or vasectomized partner)
▪ Use of at least one of the following:
a. Use of oral, injectable, transdermal, intravaginal, or implantable hormonal methods of contraception
▪ combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: Oral, intravaginal or transdermal.
▪ progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
7. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days before first administration of study drug.

E.4

Principal exclusion criteria

1. Age of onset of disease ≥25 years
2. Left ventricular ejection fraction (LVEF) <55%, on echocardiogram.
3. Subjects with a history of heart failure, ventricular arrhythmia, supraventricular tachycardia, or having a QTcF time of >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.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in spinal cord area cervical segment C2-C3 [mm2]

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, week 24 and week 48

E.5.2

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-1α, 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

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Expected normal treatment of that condition

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-02-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-09-14

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