A phase 1/2 clinical trial to Explore the Safety, Tolerability, Pharmacokinetic Profile, and Potential Efficacy of Guanabenz in Patients With Early‑Childhood Onset Vanishing White Matter (VWM)
Vanishing white matter (VWM) is caused by a genetic defect in eukaryotic translation initiation factor 2B, eIF2B. As a consequence, eIF2B activity is decreased, thereby constitutively activating the downstream integrated stress response (ISR). The drug Guanabenz has been shown to impact the ISR and to ameliorate the disease in VWM models. Guanabenz is a known α2-adrenergic antihypertensive drug with proven safety in adults and children above 12 years of age and therefore suitable for assessing the effect in VWM patients.
With CCMO / CTIS approval, we executed a clinical trial with the aim to evaluate the safety, tolerability and efficacy of Guanabenz in young children with VWM. For further details on the background and details of this study see the EU clinical trials register: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001438-25/NL.
The Guanabenz trial started May 31 2021 and ended May 31, 2025. Database lock is on July 31, 2025.
The Statistical Analysis Plan, Data Management Plan and Data Validation and Derivation plan are available.