Efficacy and Safety Evaluation of Leriglitazone in Adult Males with Cerebral Adrenoleukodystrophy: A Randomized, Placebo-Controlled Clinical Trial
- Trial ID
- 2024-515104-39-00
- Protocol
- MT-3-01
- Sponsor
- Minoryx Therapeutics S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical study is to evaluate the **efficacy** of leriglitazone compared to placebo in increasing survival in adult male subjects with cerebral adrenoleukodystrophy (cALD). This objective is clinically relevant as it directly addresses the potential of leriglitazone to improve survival outcomes in a population affected by this progressive and life-threatening neurodegenerative disorder.
Secondary objectives include:
- Evaluating the efficacy of leriglitazone compared to placebo at slowing radiological progression.
- Assessing the efficacy of leriglitazone on clinical parameters and biomarkers.
- Evaluating the effects of leriglitazone on complementary biomarkers, clinical and imaging parameters, and healthcare resource utilization.
- Assessing pharmacokinetic (PK) parameters of leriglitazone.
- Evaluating the safety and tolerability of leriglitazone compared to placebo.
Participants
The clinical trial involves a total of **25 male participants** who are aged **18 years and older**. The study population is specifically selected to include individuals with **cerebral adrenoleukodystrophy (cALD)**, a progressive condition characterized by genetic confirmation of X-ALD and the presence of GdE+ brain lesions. Participants were chosen based on their ability to provide informed consent and their willingness to adhere to contraceptive guidelines if not surgically sterilized. The trial excludes individuals with major functional disabilities, except for those who are wheelchair-bound or have total incontinence, as these are expected symptoms of adrenomyeloneuropathy (AMN) in the disease's progression. Additionally, participants must not have major cognitive impairments that would hinder their ability to participate in the study. The trial does not include a vulnerable population, and all participants have either normal adrenal function or are on appropriate steroid replacement therapy if adrenal insufficiency is present. The selection criteria ensure that the study population is homogenous in terms of health status and lifestyle considerations, focusing on those for whom hematopoietic stem cell transplantation (HSCT) is not recommended or desired.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of **leriglitazone** in adult male subjects with **cerebral adrenoleukodystrophy** (cALD). This is a randomized, double-blind, placebo-controlled study. Participants will be randomly assigned to receive either leriglitazone or a placebo, both administered as oral suspensions. The trial is expected to last until December 2026, with recruitment starting in June 2025. The primary endpoint is the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, whichever occurs first. Secondary endpoints include changes from baseline in the Loes score, time to increase of at least 1 Major Functional Disability (MFD) in the Neurological Function Score (NFS-MFD) scale, and other clinical parameters.
Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, genetic confirmation of X-ALD, and absence of major cognitive impairment. Follow-up visits will occur at regular intervals to monitor safety, efficacy, and pharmacokinetic parameters, with specific assessments at 6-month and 12-month visits. The end-of-study visit will conclude the participant's involvement, assessing final outcomes and any long-term effects. The expected length of participant involvement is up to 36 months, with conditions for early termination including significant adverse events or withdrawal of consent. Participants must adhere to contraceptive guidelines and other study requirements to remain eligible throughout the trial.
Treatment
The clinical trial involves the administration of **leriglitazone**, an experimental medication, to evaluate its efficacy and safety in adult male subjects with cerebral adrenoleukodystrophy. Leriglitazone is provided as an **oral suspension** and is administered via the oral route. The maximum daily dose is 12 milliliters, with a total maximum dose of 12 liters over the treatment period. The treatment duration is set for a maximum of 36 months. Leriglitazone is of chemical origin and is not formulated for pediatric use. The pharmaceutical form is specifically designed for oral use, ensuring ease of administration and compliance monitoring throughout the study.
The study also includes a **placebo** group to serve as a comparator for assessing the efficacy of leriglitazone. The placebo is supplied as an oral suspension, visually similar to the leriglitazone drug product, and is packaged in an amber glass bottle. The volume of the placebo suspension is adjusted based on the required clinical dose to maintain blinding. The placebo is administered following the same route and frequency as the experimental medication, ensuring consistency in the treatment protocol. Compliance with the dosing schedule is monitored to ensure the integrity of the trial results.
Efficacy
The efficacy of **leriglitazone** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is defined as the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, whichever occurs first, in subjects treated with leriglitazone compared to placebo. This endpoint is crucial for evaluating the survival benefit of the treatment.
Secondary endpoints include a variety of clinical and biomarker assessments. These involve changes from baseline in the Loes score, which measures the severity of cerebral adrenoleukodystrophy (cALD), and the time to increase of at least 1 Major Functional Disability (MFD) in the Neurological Function Score (NFS-MFD) scale. Additional assessments include changes from baseline in the Activities of Daily Living (ADL) section II of the Friedreich’s Ataxia Rating Scale (FARS), and the time to major neurocognitive impairment, defined as dementia with loss of all intellectual functions requiring constant supervision or assistance.
Further analyses will be conducted at the final analysis stage, following the primary endpoint being met. These include changes from baseline in the NFS, Symbol Digit Modalities Test (SDMT) cognitive assessment, and Clinician Global Impression - Severity and Change of symptoms (CGI-S, CGI-C). Changes in plasma neurofilament light chain protein (NfL) levels and European Quality of Life 5 Dimensions (EQ-5D-5L) scores will also be evaluated. The trial will assess pharmacokinetic parameters of leriglitazone, such as the predicted area under the time-concentration curve (AUC), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax) at the 6-month visit. Additionally, cerebrospinal fluid leriglitazone and M3 concentrations will be measured at the 12-month visit if optional CSF samples are collected.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject is able to read and understand the ICF and has provided written informed consent to participate in the study.
- Subject is male and aged ≥18 years.
- Subject has genetic confirmation of X-ALD.
- Subject has progressive cALD, defined as GdE+ brain lesions.
- Subjects for whom HSCT is not recommended by the investigator or subject is not willing to undergo HSCT.
- Subject has a Loes score ≥0.5 and ≤12 at Screening.
- 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
- 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
- Subject has normal adrenal function or appropriate steroid replacement if adrenal insufficiency is present.
- 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
- Subject who had previous bone marrow transplantation (HSCT) or treatment with ex-vivo gene therapy (eli-Cel).
- Subject has known type 1 or type 2 diabetes.
- Subject has known hypersensitivity or intolerance to pioglitazone or any other thiazolidinedione or any of the ingredients of the study drug or placebo.
- Subject is taking or has taken honokiol, pioglitazone, or other thiazolidinediones within 3 months prior to Screening.
- Subject has a requirement for treatment with a prohibited concomitant medication.
- Subject has a previous or current history of congestive heart failure.
- Subject has reduced left-ventricular ejection fraction < 50% or other clinically significant cardiac abnormalities on echocardiogram (including ventricular dilatation; aortic or mitral stenosis greater than or equal to moderate; or ventricular wall abnormality) that in the opinion of the investigator could predispose the subject to volume overload or its associated consequences.
- 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.
- Subject has moderate or severe hepatic impairment (Child-Pugh classification groups B or C).
- Subject with chronic kidney disease (CKD) of stage 3 or higher (according to the Renal Association CKD staging)
- Subject has previous or current history of cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years.
- Subject has contraindications for MRI such as having paramagnetic material in the body (e.g., aneurysm clips, pacemakers, intraocular metal, or cochlear implants).
- Subject with conditions that could modify absorption of the study drug.
- Subject with current participation in another interventional clinical study or within 1 month (or within five half-lives, whichever is longer) prior to Screening.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 01 Jun 2025 | 5 |
 Germany | Not Recruiting | 01 Jun 2025 | 5 |
 Spain | Not Recruiting | 01 Jun 2025 | 5 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
The MIN-102 Placebo is supplied as an oral suspension with similar appearance to MIN-102 drug product. MIN-102 placebo oral suspension is packaged in an amber glass bottle with filled volume based on the required clinical dose. | Placebo | N/A | — | — | — | N/A |