LERIGLITAZONE for Cerebral X-linked adrenoleukodystrophy (CALD)|Adrenoleukodystrophy

Inclusion criteria

• {"criterion_text":"- Written informed consent by parent/legal guardian, or authorized legal representative to participate in the study"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- White matter involvement as determined by cerebral MRI lesions without Gd enhancement at baseline (Population 1), or with Gd enhancement at baseline (Population 2)."}
• {"criterion_text":"- Major Functional Disabilities (MFD) score of 0, as determined by key measures in the Neurological Function Scale (NFS)."}
• {"criterion_text":"- Baseline Loes score >0 and ≤10."}
• {"criterion_text":"- Baseline Gadolinium Intensity Score (GIS) ≤3."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Glycated hemoglobin (HbA1c) within normal range."}

Exclusion criteria

• {"criterion_text":"- Other chronic neurological disease."}
• {"criterion_text":"- Permanent indwelling urinary catheter or catheter port. (Only applicable in France)"}
• {"criterion_text":"- Smoking with 25 cigarettes per day over the past 2 years until Screening (V-1). (Only applicable in France)."}
• {"criterion_text":"- Previous or current history of congestive heart failure."}
• {"criterion_text":"- Clinically significant anemia with hemoglobin <10 g/dL."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Moderate or severe hepatic impairment (groups B and C according to Child-Pugh classification)."}
• {"criterion_text":"- eGFR < 90 ml/min or any evidence of renal disease or impairment, including proteinuria or hematuria."}
• {"criterion_text":"- Pulmonary disease or cardiac disease of sufficient severity to limit participation in the study and/or completion of study procedures."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Hereditary Fructose Intolerance."}
• {"criterion_text":"- Known intolerance to pioglitazone or other thiazolidinediones."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- A positive result on laboratory tests for hepatitis B surface antigen, hepatitis C antibody or human immunodeficiency virus antibody. (Only applicable in France)"}
• {"criterion_text":"- Contraindication to MRI procedure, such as presence of ferromagnetic materials (aneurysm clips, pacemaker, intraocular metal, cochlear implant) in the body."}
• {"criterion_text":"- Conditions that could modify the absorption of the study drug."}
• {"criterion_text":"- Inability or unwillingness of parent/legal guardian or subject to comply with the study procedures."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Use of pioglitazone or other thiazolidinediones within the past 6 months prior to screening."}
• {"criterion_text":"- Use of biotin at a daily dose of >50 mg per day within the past 3 months prior to screening."}
• {"criterion_text":"- Current participation in another interventional clinical study or participation in such a study within 6 months prior to screening."}
• {"criterion_text":"- Previous HSCT."}
• {"criterion_text":"- Requirement for a prohibited concomitant medication."}
• {"criterion_text":"- Previous or current history of bladder polyps, bladder cell hyperplasia, or cancer (other than successfully treated basal cell carcinoma)."}
• {"criterion_text":"- Chronic or recurrent symptomatic urinary infections (≥2 per year over the past 2 years until Screening [V-1]). (Only applicable in France)"}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint will be the number of patients meeting \"arrested disease\" criteria at Visit 12.","definition_or_measurement_approach":"Assessed at Visit 12 (week 96) as the number of patients meeting \"arrested disease\" criteria; main objective states evaluation is determined by serial clinical and magnetic resonance imaging (MRI) investigations in pediatric subjects."}

Secondary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Change from Baseline in the composite score of specified NFS items; assessed longitudinally across visits."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Sustained change defined specifically as identical total score for NFS items 1,2,4,10,13 and no >1 change in total NFS in two consecutive visit windows (V6–8 and V11–12); alternative averaging rules specified if criterion not met."}
• {"endpoint_text":"- Change from baseline in Loes MRI severity score.","definition_or_measurement_approach":"Change from baseline in Loes MRI severity score measured by MRI assessments."}
• {"endpoint_text":"- Change from baseline in Gadolinium Intensity Score (GIS).","definition_or_measurement_approach":"Change from baseline in GIS measured by MRI with gadolinium."}
• {"endpoint_text":"- Overall survival of patients who have not undergone HSCT.","definition_or_measurement_approach":"Overall survival measured for the subset of patients who have not undergone HSCT."}
• {"endpoint_text":"- Number of patients meeting HSCT criteria","definition_or_measurement_approach":"Count of patients who meet predefined criteria for hematopoietic stem cell transplant (HSCT)."}

Germany

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

25-06-2024

Processing Time Days

27

Number Of Sites

1

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

21-06-2024

Processing Time Days

23

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

28-06-2024

Processing Time Days

30

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Minoryx Therapeutics S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

QPS Netherlands B.V.

Responsibilities

[{"code":4}]

Name

Pharmaceutical Product Development LLC

Responsibilities

[{"code":4}]

Name

CTI Clinical Trial and Consulting Services Europe GmbH

Responsibilities

[{"code":1},{"code":10},{"code":11},{"code":12},{"code":5},{"code":6},{"code":7},{"code":9}]

Name

Icon Clinical Research Limited

Responsibilities

[{"code":4}]

Name

PPD International Holdings LLC

Responsibilities

[{"code":4}]

Name

Premier Research Group S.L.

Responsibilities

[{"code":8}]

Name

Myriad RBM Inc.

Responsibilities

[{"code":4}]

Third parties

• {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"[{\"code\":4}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"[{\"code\":4}]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"[{\"code\":1},{\"code\":10},{\"code\":11},{\"code\":12},{\"code\":5},{\"code\":6},{\"code\":7},{\"code\":9}]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Laboratorium Sanitatis S.L.","duties_or_roles":"[{\"code\":14}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Massachusetts General Hospital","duties_or_roles":"[{\"code\":15,\"value\":\"Medical Image Analysis\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"[{\"code\":4}]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"[{\"code\":4}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Myriad RBM Inc.","duties_or_roles":"[{\"code\":4}]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Mde Services Group Limited","duties_or_roles":"[{\"code\":15,\"value\":\"Patient travel and reimbursement\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Premier Research Group S.L.","duties_or_roles":"[{\"code\":8}]","organisation_type":"Pharmaceutical company"}