Dimethyl fumarate for Adrenomyeloneuropathy

Inclusion criteria

• {"criterion_text":"- Men and women of 18 to 65 years old at the time of the inclusion, suffering from AMN with: - elevated plasma VLCFA - ABCD1 gene mutation identified"}
• {"criterion_text":"- Clinical signs of AMN with at least pyramidal signs in the lower limbs and difficulties to walk (EDSS score ≥ 2.0 and ≤ 6.5). EDSS score will also be re-evaluated at M12, M24 and M36."}
• {"criterion_text":"- Normal brain MRI or brain MRI showing: - abnormalities that can be observed in AMN patients without cerebral demyelination with a maximum Loes score of 4 - and/or stable (≥ 6 months) cerebral demyelination without gadolinium enhancement with a Loes score ≤ 12"}
• {"criterion_text":"- Appropriate steroid replacement if adrenal insufficiency is present"}
• {"criterion_text":"- Potential childbearing women should use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy. If oral contraceptives are used, the use of an alternative barrier method is recommended."}
• {"criterion_text":"- Likely to be able to participate in all scheduled evaluations and complete all required study procedures"}
• {"criterion_text":"- Signed and dated written informed consent to participate in the study in accordance with local regulations"}

Exclusion criteria

• {"criterion_text":"- Any progressive neurological disease other than AMN"}
• {"criterion_text":"- Leukopenia below 3.0x109 /L, lymphopenia below 0.5x109 /L or other pathological results in the complete blood count"}
• {"criterion_text":"- Suspected or confirmed progressive multifocal leukoencephalopathy (PML)"}
• {"criterion_text":"- Severe gastrointestinal disease"}
• {"criterion_text":"- Uncontrolled hepatic, renal or cardiovascular disease, or any evolutive malignancy"}
• {"criterion_text":"- Pregnancy and breast-feeding in woman and potential childbearing woman unable or unwilling to use an acceptable contraceptive method during the study"}
• {"criterion_text":"- Any new medication for AMN initiated less than three months prior to inclusion"}
• {"criterion_text":"- Contra-indications for MRI procedure such as subjects with paramagnetic materials in the body as aneurysm clips, pacemakers, intraocular metal or cochlear implants"}
• {"criterion_text":"- Inclusion in another therapeutic clinical trial for ALD"}
• {"criterion_text":"- Not easily contactable by the investigator in case of emergency or not able to call the investigator"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the mean change in 2 Minute Walk Test (2MWT) between M0 and M24. This criterion will also be evaluated at M6, M12 and at the end of the extension phase (M36). Details about the 2MWT are given in chapter 3.7.","definition_or_measurement_approach":"Mean change in 2 Minute Walk Test (2MWT) between M0 and M24; also evaluated at M6, M12 and M36. Further details and measurement procedure referenced in protocol chapter 3.7."}

Secondary endpoints

• {"endpoint_text":"- Secondary efficacy endpoints will be evaluated by the 6 Minute Walk Test (6MWT), the Time to walk 25 feet (TW25), the Postural Sway, the stair-climbing test, the strength, one questionnaire about urinary tract function (SF-Qualiveen), one questionnaire to assess fecal incontinence (RFIS), neuroimaging and biological markers. Details are given in chapter 3.7.","definition_or_measurement_approach":"Evaluation using listed clinical tests and questionnaires; details and procedures referenced in protocol chapter 3.7."}
• {"endpoint_text":"- Mean changes in 6MWT, TW25 between M0 and M24. Evaluation will also be done at M6, M12 and M36.","definition_or_measurement_approach":"Mean change comparisons from baseline (M0) to M24, with interim assessments at M6, M12 and M36."}
• {"endpoint_text":"- Mean changes in postural sway, stair-climbing test, and strength between M-1 and M24. Evaluation will also be done at M12 and M36.","definition_or_measurement_approach":"Mean change comparisons from pre-baseline (M-1) to M24; interim at M12 and M36."}
• {"endpoint_text":"- Mean changes in the SF-Qualiveen and RFIS between M0 and M24. Evaluation will also be done at M12 and M36.","definition_or_measurement_approach":"Mean change in questionnaire scores from baseline to M24 with assessments at M12 and M36."}
• {"endpoint_text":"- Mean changes in Loes score, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) parameters in the cerebral white matter on M-1 and M24. Evaluation will also be done at M12 and M36.","definition_or_measurement_approach":"Neuroimaging parameter changes (Loes score, DTI, MRS) from M-1 to M24; also measured at M12 and M36."}
• {"endpoint_text":"- Mean changes in markers of target-engagement (oxidative damage and inflammation) between M-1 and M24. Evaluation will also be done at M3 and M12.","definition_or_measurement_approach":"Biomarker assays of oxidative damage and inflammation measured at specified timepoints (M-1, M3, M12, M24)."}
• {"endpoint_text":"- Markers of neuroaxonal damage and astrocyte activation: •\tMean changes in NfL and GFAP in plasma at M-1, M3, M12, and M24, and in CSF at M0 and M24.","definition_or_measurement_approach":"Mean changes in plasma NfL and GFAP at specified visits and CSF at M0 and M24."}
• {"endpoint_text":"- Very long-chain fatty acid (VLCFA) levels •\tMean changes in C26:0 and C24:0 in plasma and CSF at M-1, and M24.","definition_or_measurement_approach":"Mean changes in plasma and CSF VLCFA species (C26:0 and C24:0) between M-1 and M24."}
• {"endpoint_text":"- Single cell RNA sequencing (scRNAseq) of PBMC •\tComparison of scRNAseq data from n=5 AMN patients (group 1: placebo), and n=10 from AMN (group 2: DMF), plus 10 samples from of age and sex-matched control adults at M-1 and M3.","definition_or_measurement_approach":"scRNAseq comparison across groups at M-1 and M3 with specified sample sizes."}
• {"endpoint_text":"- Lipidomics •\tAnalysis of glycerolipids, glycerophospholipids, and sphingolipids at M-1, M3, M12 and M24 in plasma.","definition_or_measurement_approach":"Plasma lipidomics profiling at listed timepoints."}
• {"endpoint_text":"- Metabolomics •\tAnalysis of metabolomics in stools at M-1, and M6.","definition_or_measurement_approach":"Stool metabolomics analyses at M-1 and M6."}
• {"endpoint_text":"- Metagenomics •\tIdentification in stools of the different taxa, and enzymes affected by the treatment with DMF at M-1 and M6.","definition_or_measurement_approach":"Stool metagenomics to identify taxa and enzyme changes at M-1 and M6."}

Spain

Earliest CTIS Part Ii Submission Date

05-12-2023

Latest Decision Or Authorization Date

14-02-2025

Processing Time Days

437

Number Of Sites

3

Number Of Participants

40

Primary sponsor

Full Name

Fundacio Institut D Investigacio Biomedica De Bellvitge IDIBELL

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain