Leriglitazone for Rett syndrome

Inclusion criteria

• {"criterion_text":"- 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.\n- Female subjects aged ≥5 and ≤12 years, at the time of signing the ICF.\n- Diagnosis of classical/typical RTT, according to 2010 criteria with a documented mutation of the MECP2 gene\n- Severity rating of between 10 and 36 (RTT Natural History/Clinical Severity Scale).\n- Be able to swallow the study treatment provided as an oral liquid suspension.\n- 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

• {"criterion_text":"- Actively undergoing neurological regression.\n- Conditions that could modify absorption of the study drug.\n- Known hereditary fructose intolerance (HFI).\n- Positive result in serum beta human chorionic gonadotropin (hCG) pregnancy test, if childbearing potential or lactating girl.\n- 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.\n- 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\n- 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.\n- Non-stable epilepsy/status epilepticus in the last 8 weeks.\n- Previous or current history of cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years.\n- Known type 1 or type 2 diabetes.\n- Use of pioglitazone or other thiazolidinediones within the past 6 months prior to screening.\n- Known hypersensitivity/allergic reaction or intolerance to pioglitazone or any other thiazolidinedione.\n- Known hypersensitivity/allergic reaction to the study drug substance or any of the excipients.\n- 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.\n- Clinically significant anemia with hemoglobin <10 g/dL.\n- Abnormal liver enzyme tests for aspartate transaminase (AST) or alanine transaminase (ALT) of >2.5 × the upper limit of normal (ULN).\n- Subject has moderate to severe renal impairment (GFR ˂ 60 mL/min)\n- Participation in any clinical trial within the previous 3 months.\n- Subject has mild, moderate, or severe hepatic impairment (Child-Pugh classification groups A, B or C)."}

Primary endpoints

• {"endpoint_text":"- Safety and tolerability will be assessed informally based on summary statistics calculated for TEAEs, SAEs and other safety assessments and considerations","definition_or_measurement_approach":"Assessed informally based on summary statistics calculated for treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and other safety assessments and considerations."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in Rett Syndrome Behavior Questionnaire (RSBQ), total score and each subscore.\n- Change from baseline in Vineland Adaptative Behavior Scale (VABS), total score.\n- Change from baseline in Rett Syndrome Motor Evaluation Scale (RESMES), total score.\n- Change from baseline in Communication and Symbolic Behaviour Scales - Developmental Profile - Infant Toddler (CSBS-DP-IT), total score.\n- Change from baseline in Mac Arthur I and II (reported according to age group), total score.\n- Change from baseline in Clinical Global Impression-Severity (CGI-S), total score.\n- Change from baseline in Clinical Global Impression-Improvement (CGI-I), total score.\n- Change from baseline in Rett Syndrome Caregiver Burden Inventory (RTT-CBI), total score.\n- Number of seizures per week recorded in the diary.\n- Number of apnea episodes per week recorded in the diary.\n- Number of hyperventilation episodes per week recorded in the diary.\n- Predicted area under the plasma concentration versus time curve (AUC) and maximum observed plasma concentration (Cmax) for leriglitazone.\n- Minimum observed plasma concentration (Cmin) for leriglitazone and M3.\n- Metabolic ratio.","definition_or_measurement_approach":"Endpoints are measured as change from baseline (for scales and scores) or counts per week (for seizures, apnea, hyperventilation). Pharmacokinetic endpoints include predicted AUC, Cmax, observed Cmin for leriglitazone and M3, and metabolic ratio."}

Spain

Earliest CTIS Part Ii Submission Date

30-09-2024

Latest Decision Or Authorization Date

15-07-2025

Processing Time Days

288

Number Of Sites

1

Number Of Participants

24

Primary sponsor

Full Name

Minoryx Therapeutics S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain