Evaluation of Leriglitazone Efficacy and Safety in Pediatric Patients with Rett Syndrome: A Double-Blind, Randomized, Placebo-Controlled Trial
- Trial ID
- 2024-514684-26-00
- Protocol
- MT-2-04
- Sponsor
- Minoryx Therapeutics S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and tolerability of leriglitazone in subjects with Rett Syndrome (RTT). This is clinically relevant as ensuring the safety and tolerability of a therapeutic agent is crucial before considering its efficacy in a vulnerable pediatric population.
Secondary objectives include:
- Evaluating the effect of leriglitazone in different areas of neurodevelopment in RTT.
- Assessing the impact of leriglitazone on caregiver burden.
- Investigating the effect of leriglitazone on epileptic activity.
- Evaluating the effect of leriglitazone on physiological parameters.
- Assessing the pharmacokinetics parameters of leriglitazone and its metabolite M3.
Participants
The clinical trial focuses on evaluating the safety and tolerability of leriglitazone in subjects with **Rett Syndrome**. The study population consists exclusively of female participants aged between 5 and 12 years, diagnosed with classical or typical Rett Syndrome, confirmed by a documented mutation of the MECP2 gene. Participants are required to have a severity rating between 10 and 36 on the RTT Natural History/Clinical Severity Scale. The trial population is selected based on specific inclusion criteria, including the ability to swallow the study treatment provided as an oral liquid suspension. The sponsor has not provided information regarding the total number of participants. The trial does not include male subjects and focuses on a vulnerable population, ensuring that informed consent is obtained from the parent(s) or legal guardian(s) of the participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **double-blind**, **randomized**, **placebo-controlled** study to evaluate the safety and tolerability of **leriglitazone** in pediatric patients diagnosed with **Rett Syndrome**. The trial will involve female subjects aged between 5 and 12 years, who have a documented mutation of the MECP2 gene and meet specific severity criteria. The study will be conducted over an estimated duration from October 2024 to November 2025, with recruitment starting in October 2024. Participants will be randomly assigned to receive either the active drug, leriglitazone, or a placebo, both administered as an oral suspension.
The trial will include several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess overall outcomes. The primary endpoint will focus on safety and tolerability, assessed through summary statistics of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Secondary endpoints will evaluate changes from baseline in various behavioral and clinical scales, such as the Rett Syndrome Behavior Questionnaire and the Vineland Adaptive Behavior Scale, among others.
Participants are expected to be involved in the study for a maximum treatment period of 36 weeks. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or withdrawal of consent by the participant's legal guardian. The study aims to provide valuable insights into the potential benefits and risks of leriglitazone in managing symptoms of Rett Syndrome in the pediatric population.
Treatment
The clinical trial involves the administration of **Leriglitazone**, an experimental medication, in the form of an oral suspension. The pharmaceutical form is specifically designed for oral administration, with the option for use via nasogastric tube or percutaneous endoscopic gastrostomy tube. The maximum daily dose of Leriglitazone is 10 ml, with a total maximum dose of 2.52 liters over the treatment period. The treatment duration is set for a maximum of 36 weeks. The active substance, Leriglitazone, is of chemical origin and is provided by the organization MINORYX. The medication is packaged in a manner suitable for maintaining its stability and integrity throughout the study.
The study also includes a **placebo** control, which is supplied as an oral suspension with a similar appearance to the Leriglitazone drug product. The placebo is packaged in an amber glass bottle, with the volume filled based on the required clinical dose to ensure blinding. The placebo is administered via the same routes as the experimental medication, ensuring consistency in administration methods across study participants. The placebo serves as a comparator treatment to evaluate the efficacy and safety of Leriglitazone in the context of the study's objectives.
Efficacy
Efficacy in the clinical trial of Leriglitazone for pediatric **Rett Syndrome** will be assessed using several secondary endpoints. These include changes from baseline in various scales and questionnaires: the Rett Syndrome Behavior Questionnaire (RSBQ), Vineland Adaptive Behavior Scale (VABS), Rett Syndrome Motor Evaluation Scale (RESMES), Communication and Symbolic Behaviour Scales - Developmental Profile - Infant Toddler (CSBS-DP-IT), Mac Arthur I and II, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement (CGI-I). Additionally, the Rett Syndrome Caregiver Burden Inventory (RTT-CBI) will be used to evaluate caregiver burden. The number of seizures, apnea episodes, and hyperventilation episodes per week will be recorded in a diary. Pharmacokinetic parameters such as the predicted area under the plasma concentration versus time curve (AUC), maximum observed plasma concentration (Cmax), minimum observed plasma concentration (Cmin) for Leriglitazone and its metabolite M3, and the metabolic ratio will also be measured.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Free written Informed Consent Form (ICF) by their parent(s)/legal guardian(s) or authorized legal representative(s) prior to any procedure required by the study.
- Female subjects aged ≥5 and ≤12 years, at the time of signing the ICF.
- Diagnosis of classical/typical RTT, according to 2010 criteria with a documented mutation of the MECP2 gene
- Severity rating of between 10 and 36 (RTT Natural History/Clinical Severity Scale).
- Be able to swallow the study treatment provided as an oral liquid suspension.
- A female subject is eligible if she meets one of the following criteria: − is of non-childbearing potential, see Contraception Requirements; or − is of childbearing potential and agrees to use an accepted contraceptive method from at least 4 weeks prior to Enrolment until 4 weeks after the End of Treatment (EOT) or Premature Discontinuation Visit (PDV), see Contraception Requirements
Exclusion Criteria
- Actively undergoing neurological regression.
- Known hypersensitivity/allergic reaction or intolerance to pioglitazone or any other thiazolidinedione.
- Known hypersensitivity/allergic reaction to the study drug substance or any of the excipients.
- Has a requirement for treatment with a prohibited concomitant medication, specified in Protocol (Previous and Concomitant Medication), including the antiepileptic medication (Carbamazepine, Clobazam, Perampanel and/or Zonisamide), the antipsychotic medication (Risperidone), and medications known to prolong QTc interval.
- Clinically significant anemia with hemoglobin <10 g/dL.
- Abnormal liver enzyme tests for aspartate transaminase (AST) or alanine transaminase (ALT) of >2.5 × the upper limit of normal (ULN).
- Subject has moderate to severe renal impairment (GFR ˂ 60 mL/min)
- Participation in any clinical trial within the previous 3 months.
- Subject has mild, moderate, or severe hepatic impairment (Child-Pugh classification groups A, B or C).
- Conditions that could modify absorption of the study drug.
- Known hereditary fructose intolerance (HFI).
- Positive result in serum beta human chorionic gonadotropin (hCG) pregnancy test, if childbearing potential or lactating girl.
- Other medical, neurologic, psychiatric, or social condition that, in the opinion of the Investigator, is likely to unfavourably alter risk-benefit of study participation, confound interpretation of safety or efficacy results, or interfere with the satisfactory completion of study requirements.
- Has any of the following: − QT interval (corrected by Bazett’s formula) of >460 ms at Screening or Baseline (before dosing). − History of a risk factor for torsade de pointes (e.g., heart failure or family history of long QT syndrome). − History of clinically significant QT prolongation that is deemed to put the subject at increased risk of clinically significant QT prolongation or treatment for known QTc prolongation with drugs such as betablockers
- Reduced left-ventricular ejection fraction (LVEF) ˂ 50%, or other clinically significant cardiac abnormalities on echocardiogram that in the Investigator’s opinion could predispose the subject to volume overload or its attendant consequences.
- Non-stable epilepsy/status epilepticus in the last 8 weeks.
- Previous or current history of cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years.
- Known type 1 or type 2 diabetes.
- Use of pioglitazone or other thiazolidinediones within the past 6 months prior to screening.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 01 Oct 2024 | 24 |
Sites & Investigators
Research 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 |