Double-blind, randomized, placebo-controlled study of Leriglitazone in pediatric Rett Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Minoryx Therapeutics S.L.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Female

Therapeutic area

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

Trial duration

29 Oct 2024 → ongoing

Decision date (initial)

2024-10-08

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To evaluate the safety and tolerability of leriglitazone in RTT subjects.

Secondary objectives 5

1. To evaluate the effect of leriglitazone in different areas of neurodevelopment in RTT.
2. To evaluate the impact of leriglitazone in caregiver burden.
3. To evaluate the effect of leriglitazone on epileptic activity.
4. To evaluate the effect of leriglitazone on physiological parameters.
5. To assess the pharmacokinetics parameters of leriglitazone and M3.

Conditions and MedDRA coding

Rett Syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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.
2. Female subjects aged ≥5 and ≤12 years, at the time of signing the ICF.
3. Diagnosis of classical/typical RTT, according to 2010 criteria with a documented mutation of the MECP2 gene
4. Severity rating of between 10 and 36 (RTT Natural History/Clinical Severity Scale).
5. Be able to swallow the study treatment provided as an oral liquid suspension.
6. 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 19

1. Actively undergoing neurological regression.
2. Known hypersensitivity/allergic reaction or intolerance to pioglitazone or any other thiazolidinedione.
3. Known hypersensitivity/allergic reaction to the study drug substance or any of the excipients.
4. 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.
5. Clinically significant anemia with hemoglobin <10 g/dL.
6. Abnormal liver enzyme tests for aspartate transaminase (AST) or alanine transaminase (ALT) of >2.5 × the upper limit of normal (ULN).
7. Subject has moderate to severe renal impairment (GFR ˂ 60 mL/min)
8. Participation in any clinical trial within the previous 3 months.
9. Subject has mild, moderate, or severe hepatic impairment (Child-Pugh classification groups A, B or C).
10. Conditions that could modify absorption of the study drug.
11. Known hereditary fructose intolerance (HFI).
12. Positive result in serum beta human chorionic gonadotropin (hCG) pregnancy test, if childbearing potential or lactating girl.
13. 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.
14. 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
15. 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.
16. Non-stable epilepsy/status epilepticus in the last 8 weeks.
17. Previous or current history of cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years.
18. Known type 1 or type 2 diabetes.
19. Use of pioglitazone or other thiazolidinediones within the past 6 months prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability will be assessed informally based on summary statistics calculated for TEAEs, SAEs and other safety assessments and considerations

Secondary endpoints 14

1. Change from baseline in Rett Syndrome Behavior Questionnaire (RSBQ), total score and each subscore.
2. Change from baseline in Vineland Adaptative Behavior Scale (VABS), total score.
3. Change from baseline in Rett Syndrome Motor Evaluation Scale (RESMES), total score.
4. Change from baseline in Communication and Symbolic Behaviour Scales - Developmental Profile - Infant Toddler (CSBS-DP-IT), total score.
5. Change from baseline in Mac Arthur I and II (reported according to age group), total score.
6. Change from baseline in Clinical Global Impression-Severity (CGI-S), total score.
7. Change from baseline in Clinical Global Impression-Improvement (CGI-I), total score.
8. Change from baseline in Rett Syndrome Caregiver Burden Inventory (RTT-CBI), total score.
9. Number of seizures per week recorded in the diary.
10. Number of apnea episodes per week recorded in the diary.
11. Number of hyperventilation episodes per week recorded in the diary.
12. Predicted area under the plasma concentration versus time curve (AUC) and maximum observed plasma concentration (Cmax) for leriglitazone.
13. Minimum observed plasma concentration (Cmin) for leriglitazone and M3.
14. Metabolic ratio.

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 Mistry

Public contact point

Organisation

Minoryx Therapeutics S.L.

Contact name

Silvia Pascual

Locations

1 EU/EEA country · 1 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 27 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