Guanabenz in VWM: extension study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 Dec 2025 → ongoing

Decision date (initial)

2025-11-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacokinetic

To evaluate long-term efficacy of guanabenz in patients with early childhood onset (≤ 6 years) VWM as compared to matched historical controls.

Secondary objectives 6

1. To identify overall survival in patients with VWM receiving guanabenz as compared to matched historical controls.
2. To determine how disability and QoL change over time in patients with VWM receiving guanabenz as compared to matched historical controls.
3. To identify how MRI parameters relevant to brain white matter integrity change over time in patients with VWM receiving guanabenz.
4. To evaluate the PK profile of guanabenz in VWM patients, and compare the PK profiles of the VWM1 guanabenz capsules versus the new batch of guanabenz capsules used in VWM2.
5. To investigate plasma guanabenz levels for determination of the optimal guanabenz treatment dose.
6. To evaluate the long-term safety and tolerability profile of guanabenz in patients with VWM.

Conditions and MedDRA coding

Vanishing white matter

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 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.
2. Patients must have completed the VWM1 study
3. Live within reasonable travel distance from Amsterdam.

Exclusion criteria 5

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 6

1. Overall survival rate.
2. 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).
3. 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)
4. Guanabenz PK parameters in plasma, such as Cmax, AUC, half-life (T1/2), and predicted trough concentration (Ctrough) at steady state
5. Guanbenz exposure analyzed versus the primary endpoint.
6. 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.

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

Meibergdreef 9

City

Amsterdam

Postcode

1105 AZ

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Prof. Dr. M.S. van der Knaap

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Prof. Dr. M.S. van der Knaap

Locations

1 EU/EEA country · 1 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 28 files

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

Application history

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