Guanabenz acetate for Vanishing white matter | Leukodystrophy

Inclusion criteria

• {"criterion_text":"- Each patient’s parents/legal guardians must sign an ICF indicating that they understand the purpose of and procedures required for this study, are willing for their child to participate in the study and attend all scheduled assessments (on site or by video consultation as indicated per protocol), and are willing and able to comply with all study-related procedures, including maintaining contact with the site for the duration of the trial, and adhere to the prohibitions and restrictions as specified in the protocol.\n- Patients must have completed the VWM1 study\n- Live within reasonable travel distance from Amsterdam."}

Exclusion criteria

• {"criterion_text":"- Presence of an unrelated serious condition (e.g. newly identified other genetic defect, cardiac, liver or kidney disease).\n- Participation in another clinical study with therapeutic intervention (with the exception of VWM1).\n- Unable or unwilling to follow all details of the study protocol.\n- Unable to undergo MRI due to metal-containing implants, such as cochlea implant, neurostimulator or pacemaker.\n- Family situation in which adherence to the study medication or follow-up procedures cannot be guaranteed."}

Primary endpoints

• {"endpoint_text":"- Ambulation: change from baseline at VWM1 study start to the end of the VWM2 study in the ability to walk at least 10 steps without and with light support of one hand as assessed by clinical examination, by the Gross Motor Function Measure, version 88 (GMFM 88), item E, number 68-88 or Health Utility Index (HUI) item 9, score 1-4, depending on available data in historical controls.","definition_or_measurement_approach":"Change from baseline (VWM1 start) to end of VWM2 in ability to walk ≥10 steps without and with light support of one hand; assessed by clinical examination, GMFM-88 (item E, numbers 68-88) or HUI item 9 (score 1-4) depending on available historical control data."}

Secondary endpoints

• {"endpoint_text":"- Overall survival rate.","definition_or_measurement_approach":"Overall survival measured as survival status/time; compared to matched historical controls."}
• {"endpoint_text":"- Changes in quality of life (QoL) and disability of participants, measured from the start of VWM1 to the end of VWM2, assessed using: GMFM 88, GMFC-MLD, GMFCS, MACS, CFCS, ELFC-MLD, EDACS, HUI, LIPS, Vineland-3, EQ-5D-5L, and EQ-5D-Y (proxy and self-reporting from 8 years old).","definition_or_measurement_approach":"QoL and disability changes assessed longitudinally using listed validated scales/instruments; EQ-5D-Y self-report from age ≥8 (proxy available)."}
• {"endpoint_text":"- Changes in brain MRI parameters from baseline at VWM1 study start to the end of the VMW2 study:  Diffusion Tensor Imaging (DTI)  Chemical Shift Imaging (CSI)  Neurite Orientation Dispersion and Density Imaging (NODDI)  Myelin Water Fraction Imaging (MWFI)","definition_or_measurement_approach":"Serial MRI measures (DTI, CSI, NODDI, MWFI) compared from baseline to end of study to assess white matter integrity changes."}
• {"endpoint_text":"- Guanabenz PK parameters in plasma, such as Cmax, AUC, half-life (T1/2), and predicted trough concentration (Ctrough) at steady state","definition_or_measurement_approach":"Pharmacokinetic profiling in plasma measuring Cmax, AUC, T1/2, and predicted Ctrough at steady state."}
• {"endpoint_text":"- Guanbenz exposure analyzed versus the primary endpoint.","definition_or_measurement_approach":"Exposure–response analysis comparing guanabenz plasma exposure metrics to primary ambulation endpoint."}
• {"endpoint_text":"- Frequency, severity, and daily life impact of all AEs, including AEs of special interest, occurring from the start of VWM2 study treatment until the end of the VWM2 study.","definition_or_measurement_approach":"Safety monitoring of adverse events (frequency, severity, impact) collected from treatment start to study end, including AEs of special interest."}

Netherlands

Earliest CTIS Part Ii Submission Date

13-11-2025

Latest Decision Or Authorization Date

26-11-2025

Processing Time Days

13

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands