LERIGLITAZONE for Cerebral adrenoleukodystrophy (cALD)

Inclusion criteria

• {"criterion_text":"- Subject is able to read and understand the ICF and has provided written informed consent to participate in the study.\n- Subject is surgically sterilized. If subject is not surgically sterilized, they must be willing to use adequate contraception when engaging in sexual intercourse with a partner who is pregnant or has the potential to become pregnant, and not donate sperm from the first dose of the study drug until at least 90 days after the last dose. Adequate contraception is defined as a diaphragm or cervical cap, or a male condom; this should be combined with hormonal contraceptives or an intrauterine device for a nonpregnant partner with the potential to become pregnant. Total abstinence, in accordance with the lifestyle of the subject, is also acceptable.\n- Subject is male and aged ≥18 years.\n- Subject has genetic confirmation of X-ALD.\n- Subject has progressive cALD, defined as GdE+ brain lesions.\n- Subjects for whom HSCT is not recommended by the investigator or subject is not willing to undergo HSCT.\n- Subject has a Loes score ≥0.5 and ≤12 at Screening.\n- Subject does not have major functional disability in the Major Functional Disabilities-Neurological Function Score (MFD-NFS), other than “wheelchair bound” or “total incontinence”, which will be allowed as these are considered expected symptoms of AMN in the time course of the disease\n- Subject does not have major cognitive impairment which would impair his ability to take part in the study as determined by the investigator at screening\n- Subject has normal adrenal function or appropriate steroid replacement if adrenal insufficiency is present."}

Exclusion criteria

• {"criterion_text":"- Subject who had previous bone marrow transplantation (HSCT) or treatment with ex-vivo gene therapy (eli-Cel).\n- Subject with chronic kidney disease (CKD) of stage 3 or higher (according to the Renal Association CKD staging)\n- Subject has previous or current history of cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years.\n- Subject has contraindications for MRI such as having paramagnetic material in the body (e.g., aneurysm clips, pacemakers, intraocular metal, or cochlear implants).\n- Subject with conditions that could modify absorption of the study drug.\n- Subject with current participation in another interventional clinical study or within 1 month prior to Screening.\n- Subject with other medical, neuropsychiatric or social conditions that, in the opinion of the investigator, are likely to adversely affect the risk-benefit of study participation, interfere with study compliance, or confound the study results.\n- Subject has known type 1 or type 2 diabetes.\n- Subject has known hypersensitivity or intolerance to pioglitazone or any other thiazolidinedione.\n- Subject is taking or has taken honokiol, pioglitazone, or other thiazolidinediones within 3 months prior to Screening.\n- Subject has a requirement for treatment with a prohibited concomitant medication.\n- Subject has a previous or current history of congestive heart failure.\n- Subject has reduced left-ventricular ejection fraction or other clinically significant cardiac abnormalities on echocardiogram that in the opinion of the investigator could predispose the subject to volume overload or its associated consequences\n- Subjects with clinically significant anemia (hemoglobin <12.5 g/dL), abnormal liver enzyme tests for aspartate transaminase (AST) or alanine transaminase (ALT) of >2.5 × the upper limit of normal (ULN) at Screening.\n- Subject has moderate or severe hepatic impairment (Child-Pugh classification groups B or C)."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, whichever comes earlier, in subjects treated with leriglitazone compared to placebo.","definition_or_measurement_approach":"Time-to-event endpoint measured as time from randomisation to death or to becoming bedridden with requirement for permanent ventilatory support (whichever occurs first); comparison between leriglitazone and placebo."}

Secondary endpoints

• {"endpoint_text":"- Change from Baseline in Loes score.","definition_or_measurement_approach":"Radiological Loes score change from baseline measured on MRI scans."}
• {"endpoint_text":"- To evaluate the efficacy of leriglitazone compared to placebo on the following clinical parameters: - Time to increase of at least 1 MFD in the NFS-MFD scale - Change from Baseline in ADL – section II of the Friedreich’s Ataxia Rating Scale (FARS) - Time to Major Neurocognitive Impairment – defined as dementia with loss of all intellectual functions requiring constant supervision or assistance","definition_or_measurement_approach":"Clinical measures: (a) time-to-event for increase of ≥1 Major Functional Disability on NFS-MFD; (b) change from baseline in ADL (FARS section II); (c) time-to-event for major neurocognitive impairment as defined."}
• {"endpoint_text":"- Performed at final analysis (with the analysis following the primary endpoint being met): • Change from Baseline of NFS • Change from Baseline of Symbol Digit Modalities Test (SDMT) cognitive assessment • Clinician Global Impression - Severity and Clinician Global Impression - Change of symptoms (CGI-S, CGI-C, and anchored scale for CGI-C) • Change from Baseline in plasma neurofilament light chain protein (NfL) • Change from Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L)","definition_or_measurement_approach":"Various clinical and biomarker assessments at final analysis: NFS and SDMT score changes from baseline; CGI-S/CGI-C assessments by clinician; plasma NfL change from baseline; EQ-5D-5L change from baseline."}
• {"endpoint_text":"- To evaluate the effects of leriglitazone on complementary biomarkers, and clinical and imaging parameters","definition_or_measurement_approach":"Exploratory analyses of complementary biomarkers and additional clinical and imaging parameters (measurement methods per protocol-defined biomarker assays and imaging assessments)."}
• {"endpoint_text":"- To assess PK parameters of leriglitazone (plasma) – predicted area under the time-concentration curve (AUC), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax) (only at the 6-month visit).","definition_or_measurement_approach":"Pharmacokinetic sampling at month 6 to estimate plasma AUC, Cmin and Cmax."}
• {"endpoint_text":"- Cerebrospinal fluid leriglitazone and M3 concentrations change from Baseline (only at 12-month visit and if optional CSF samples have been collected).","definition_or_measurement_approach":"Optional CSF sampling at month 12 to measure change from baseline in CSF concentrations of leriglitazone and metabolite M3."}

Spain

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

24-10-2024

Processing Time Days

27

Number Of Sites

1

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

21-10-2024

Latest Decision Or Authorization Date

29-10-2024

Processing Time Days

8

Number Of Sites

1

Number Of Participants

5

France

Earliest CTIS Part Ii Submission Date

03-10-2024

Latest Decision Or Authorization Date

28-10-2024

Processing Time Days

25

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Minoryx Therapeutics S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Premier Research Group S.L.

Responsibilities

Sponsor duties codes: 12,13,5,6,8 (as listed in CTIS third party entry)

Third parties

• {"country":"Spain","full_name":"Premier Research Group S.L.","duties_or_roles":"12,13,5,6,8","organisation_type":"Pharmaceutical company"}