A clinical study to assess the efficacy and safety of leriglitazone in adult male subjects with cerebral adrenoleukodystrophy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Minoryx Therapeutics S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Dec 2024 → ongoing

Decision date (initial)

2024-10-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Minoryx Therapeutics S.L.

External identifiers

EU CT number

2024-515104-39-00

ClinicalTrials.gov

NCT05819866

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To evaluate the efficacy of leriglitazone compared to placebo at increasing survival

Secondary objectives 5

1. To evaluate the efficacy of leriglitazone compared to placebo at slowing radiological progression.
2. To evaluate the efficacy of leriglitazone compared to placebo on clinical parameters and biomarkers.
3. To evaluate the effects of leriglitazone compared to placebo on complementary biomarkers, clinical and imaging parameters and healthcare resource utilization.
4. To assess PK parameters of leriglitazone.
5. To evaluate the safety and tolerability of leriglitazone compared to placebo.

Conditions and MedDRA coding

Cerebral adrenoleukodystrophy (cALD)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subject is able to read and understand the ICF and has provided written informed consent to participate in the study.
2. Subject is male and aged ≥18 years.
3. Subject has genetic confirmation of X-ALD.
4. Subject has progressive cALD, defined as GdE+ brain lesions.
5. Subjects for whom HSCT is not recommended by the investigator or subject is not willing to undergo HSCT.
6. Subject has a Loes score ≥0.5 and ≤12 at Screening.
7. Subject does not have major functional disability in the Major Functional Disabilities-Neurological Function Score (MFD-NFS), other than “wheelchair bound” or “total incontinence”, which will be allowed as these are considered expected symptoms of AMN in the time course of the disease
8. Subject does not have major cognitive impairment which would impair his ability to take part in the study as determined by the investigator at screening
9. Subject has normal adrenal function or appropriate steroid replacement if adrenal insufficiency is present.
10. Subject is surgically sterilized. If subject is not surgically sterilized, they must be willing to use adequate contraception when engaging in sexual intercourse with a partner who is pregnant or has the potential to become pregnant, and not donate sperm from the first dose of the study drug until at least 90 days after the last dose. Adequate contraception is defined as a diaphragm or cervical cap, or a male condom; this should be combined with hormonal contraceptives or an intrauterine device for a nonpregnant partner with the potential to become pregnant. Total abstinence, in accordance with the lifestyle of the subject, is also acceptable.

Exclusion criteria 15

1. Subject who had previous bone marrow transplantation (HSCT) or treatment with ex-vivo gene therapy (eli-Cel).
2. Subject has known type 1 or type 2 diabetes.
3. Subject has known hypersensitivity or intolerance to pioglitazone or any other thiazolidinedione.
4. Subject is taking or has taken honokiol, pioglitazone, or other thiazolidinediones within 3 months prior to Screening.
5. Subject has a requirement for treatment with a prohibited concomitant medication.
6. Subject has a previous or current history of congestive heart failure.
7. Subject has reduced left-ventricular ejection fraction or other clinically significant cardiac abnormalities on echocardiogram that in the opinion of the investigator could predispose the subject to volume overload or its associated consequences
8. Subjects with clinically significant anemia (hemoglobin <12.5 g/dL), abnormal liver enzyme tests for aspartate transaminase (AST) or alanine transaminase (ALT) of >2.5 × the upper limit of normal (ULN) at Screening.
9. Subject has moderate or severe hepatic impairment (Child-Pugh classification groups B or C).
10. Subject with chronic kidney disease (CKD) of stage 3 or higher (according to the Renal Association CKD staging)
11. Subject has previous or current history of cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years.
12. Subject has contraindications for MRI such as having paramagnetic material in the body (e.g., aneurysm clips, pacemakers, intraocular metal, or cochlear implants).
13. Subject with conditions that could modify absorption of the study drug.
14. Subject with current participation in another interventional clinical study or within 1 month prior to Screening.
15. Subject with other medical, neuropsychiatric or social conditions that, in the opinion of the investigator, are likely to adversely affect the risk-benefit of study participation, interfere with study compliance, or confound the study results.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, whichever comes earlier, in subjects treated with leriglitazone compared to placebo.

Secondary endpoints 6

1. Change from Baseline in Loes score.
2. To evaluate the efficacy of leriglitazone compared to placebo on the following clinical parameters: - Time to increase of at least 1 MFD in the NFS-MFD scale - Change from Baseline in ADL – section II of the Friedreich’s Ataxia Rating Scale (FARS) - Time to Major Neurocognitive Impairment – defined as dementia with loss of all intellectual functions requiring constant supervision or assistance
3. Performed at final analysis (with the analysis following the primary endpoint being met): • Change from Baseline of NFS • Change from Baseline of Symbol Digit Modalities Test (SDMT) cognitive assessment • Clinician Global Impression - Severity and Clinician Global Impression - Change of symptoms (CGI-S, CGI-C, and anchored scale for CGI-C) • Change from Baseline in plasma neurofilament light chain protein (NfL) • Change from Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L)
4. To evaluate the effects of leriglitazone on complementary biomarkers, and clinical and imaging parameters
5. To assess PK parameters of leriglitazone (plasma) – predicted area under the time-concentration curve (AUC), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax) (only at the 6-month visit).
6. Cerebrospinal fluid leriglitazone and M3 concentrations change from Baseline (only at 12-month visit and if optional CSF samples have been collected).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Minoryx Therapeutics S.L.

Sponsor organisation

Minoryx Therapeutics S.L.

Address

Carrer D Ernest Lluch 32 Tcm 2

City

Mataro

Postcode

08302

Country

Spain

Scientific contact point

Organisation

Minoryx Therapeutics S.L.

Contact name

Arun

Public contact point

Organisation

Minoryx Therapeutics S.L.

Contact name

Silvia Pascual

Third parties 1

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 84 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications