An Open-Label, Multicenter Study in Male Pediatric Patients with Cerebral X-Linked Adrenoleukodystrophy (Cald) to Assess the Effects of MIN-102 Treatment on Disease Progression Prior to Human Stem Cell Transplant (Hsct)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Minoryx Therapeutics S.L.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

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

Trial duration

13 Sep 2019 → ongoing

Decision date (initial)

2024-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Minoryx Therapeutics S.L.

External identifiers

EU CT number

2024-513774-21-00

EudraCT number

2019-000654-59

ClinicalTrials.gov

NCT04528706

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy, Therapy

To evaluate whether MIN-102 can arrest disease progression of cALD at week 96, as determined by serial clinical and magnetic resonance imaging (MRI) investigations in pediatric subjects.

Secondary objectives 1

1. To determine the effects of MIN-102 treatment on further clinical and imaging parameters. • To assess the changes in neurological function. • To evaluate the effects of pre-HSCT MIN-102 treatment on: - Loes scores - Gadolinium intensity score (GIS) - Overall survival of patients who have not undergone HSCT - Number of patients meeting HSCT criteria • To assess the pharmacokinetics (PK), safety, tolerability, and palatability of MIN-102 in pediatric subjects

Conditions and MedDRA coding

CEREBRAL X-LINKED ADRENOLEUKODYSTROPHY (CALD)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002106-PIP01-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent by parent/legal guardian, or authorized legal representative to participate in the study
2. Males aged ≥2 and ≤12 years with a diagnosis of X-linked ALD based on genetic testing; or, in absence of genetic testing, elevation of VLCFA and confirmed by family history of X-ALD with clinical symptoms and elevation of VLCFA or by genetic testing of a family member.
3. White matter involvement as determined by cerebral MRI lesions without Gd enhancement at baseline (Population 1), or with Gd enhancement at baseline (Population 2).
4. Major Functional Disabilities (MFD) score of 0, as determined by key measures in the Neurological Function Scale (NFS).
5. Baseline Loes score >0 and ≤10.
6. Baseline Gadolinium Intensity Score (GIS) ≤3.
7. No signs or symptoms of adrenal insufficiency and morning cortisol and aldosterone levels within normal laboratory ranges for age, or appropriate steroid replacement if adrenal insufficiency is present. A history of adrenal insufficiency is not exclusionary if the foregoing is currently met.
8. Glycated hemoglobin (HbA1c) within normal range.

Exclusion criteria 26

1. Other chronic neurological disease.
2. Known intolerance to pioglitazone or other thiazolidinediones.
3. Use of pioglitazone or other thiazolidinediones within the past 6 months prior to screening.
4. Use of biotin at a daily dose of >50 mg per day within the past 3 months prior to screening.
5. Current participation in another interventional clinical study or participation in such a study within 6 months prior to screening.
6. Previous HSCT.
7. Requirement for a prohibited concomitant medication.
8. Previous or current history of bladder polyps, bladder cell hyperplasia, or cancer (other than successfully treated basal cell carcinoma).
9. Chronic or recurrent symptomatic urinary infections (≥2 per year over the past 2 years until Screening [V-1]). (Only applicable in France)
10. Permanent indwelling urinary catheter or catheter port. (Only applicable in France)
11. Smoking with 25 cigarettes per day over the past 2 years until Screening (V-1). (Only applicable in France).
12. Previous or current history of congestive heart failure.
13. Clinically significant anemia with hemoglobin <10 g/dL.
14. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level >2 times the ULN or total bilirubin >1.5 times the ULN (unless due to Gilbert's syndrome).
15. Moderate or severe hepatic impairment (groups B and C according to Child-Pugh classification).
16. eGFR < 90 ml/min or any evidence of renal disease or impairment, including proteinuria or hematuria.
17. Pulmonary disease or cardiac disease of sufficient severity to limit participation in the study and/or completion of study procedures.
18. Reduced left-ventricular ejection fraction 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.
19. Hereditary Fructose Intolerance.
20. History of diabetes, or glycated hemoglobin (HbA1c) levels >6.4% and fasting blood glucose levels ≤ 0.9 times the lower limit of normal and ≥ 1.1 times the upper limit of normal at Screening
21. A positive result on laboratory tests for hepatitis B surface antigen, hepatitis C antibody or human immunodeficiency virus antibody. (Only applicable in France)
22. Contraindication to MRI procedure, such as presence of ferromagnetic materials (aneurysm clips, pacemaker, intraocular metal, cochlear implant) in the body.
23. Conditions that could modify the absorption of the study drug.
24. Inability or unwillingness of parent/legal guardian or subject to comply with the study procedures.
25. Inability or unwillingness of parent/legal guardian or subject to resume standard of care at a local center once study is complete or criteria for HSCT is met and treatment available.
26. Other medical, neurologic, psychiatric, or social condition that, in the opinion of the investigator, is likely to unfavorably alter risk-benefit of study participation, confound interpretation of safety or efficacy results, or interfere with the satisfactory completion of study requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint will be the number of patients meeting "arrested disease" criteria at Visit 12.

Secondary endpoints 6

1. Sustained change from Baseline in the score composed of NFS items 1 (hearing/auditory processing), 2 (aphasia/apraxia), 4 (vision impairment), 10 (spastic gait) and 13 (incontinence).
2. Sustained change from Baseline in total NFS score “Sustained change” is defined as the same total score for NFS items 1, 2, 4, 10, and 13 and no change >1 in NFS total score observed in two the consecutive Visits 6–8, and Visits 11-12, respectively. If “sustained change” definition is not met, the average of the two scores of Visit 6 and 8, and Visit 11 and 12, respectively, will be used. If NFS total score differs by 1 point between V6-8, or V11-12, the higher of the two scores is used.
3. Change from baseline in Loes MRI severity score.
4. Change from baseline in Gadolinium Intensity Score (GIS).
5. Overall survival of patients who have not undergone HSCT.
6. Number of patients meeting HSCT criteria

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Minoryx Therapeutics S.L.

Sponsor organisation

Minoryx Therapeutics S.L.

Address

Calle D'Ernest Lluch 32 Tcm 3

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

Sílvia Pascual

Third parties 10

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 9 files

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

Application history

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