A Study of VGL101 in Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia

Phase 2

Active, not recruiting

Brief Summary: This is a multicenter, open-label study to assess the safety and tolerability of iluzanebart (also referred to as VGL101) in subjects with documentation of a gene mutation in the CSF1R gene for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and to evaluate the effects of iluzanebart on imaging and biomarkers of disease progression in subjects with ALSP. Participants will receive infusions of iluzanebart approximately every 4 weeks for 1 year. The study includes a 52-week, open-label Core Study, followed by a Long-Term Extension (LTE), which provides subjects who complete the original 52-week study (Core Study) with the option to continue treatment for up to an additional 2 years.

Recruitment & Eligibility

Inclusion Criteria

Participants who have documentation of a gene mutation in the CSF1R gene
Participants fulfill both (Parts A and B) of the following criteria:
1. The participant has more than 2 findings of clinical signs or symptoms in the following categories:
  1. Cognitive impairment or psychiatric problem
  2. Pyramidal signs on neurological examination
  3. Extrapyramidal signs, such as rigidity.
  4. Epilepsy
2. MRI findings consistent with ALSP, specifically, bilateral cerebral white matter lesions with or without thinning of the corpus callosum, on the Screening MRI.
The participant must have a study partner (i.e., caregiver, family member, friend, etc.) who, in the investigator's judgment, has frequent and sufficient contact with the subject so as to be able to provide accurate information about the participant's health and cognitive and functional abilities. The study partner must be willing to sign a study partner ICF.

Key

Exclusion Criteria

The participant has any neurological disease that poses a risk to the participant or can produce cognitive, motor, or behavioral impairment similar to ALSP, including, but not limited to, brain tumor, hydrocephalus, Alzheimer's disease, frontotemporal dementia (FTD), ALS, stroke, Huntington disease, multiple sclerosis, Parkinson's disease, and Down syndrome.
Participant with any condition or situation that, in the opinion of the investigator or sponsor medical personnel, may place the subject at significant risk, confound the study results, or interfere significantly with the participant's participation in the study.

Arm && Interventions

Group	Intervention	Description
VGL101	VGL101	Solution administered via Intravenous Infusion (IV)

Primary Outcome Measures

Name	Time	Method
Core Study Adverse Events	Week 24 and Week 52	To evaluate the safety and tolerability of iluzanebart for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) by adverse events in the Core Study
Long-Term Extension Adverse Events	Weeks 52, 76, 100, 124, and 148	To evaluate the safety and tolerability of iluzanebart for the treatment of ALSP by adverse events in the Long-Term Extension

Secondary Outcome Measures

Name	Time	Method
To evaluate the effects of iluzanebart on biomarkers of disease progression in participants with ALSP in the Core Study	Week 24 and Week 52	Change from Baseline to Week 24 and Week 52 in neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and blood
To evaluate the effects of iluzanebart on the ALSP on biomarkers of disease progression and clinical outcomes in patients with ALSP in the Core Study	Week 24 and Week 52	Correlations of Week 24 and Week 52 biomarker changes and clinical outcomes
To evaluate the effects of iluzanebart on biomarkers of target engagement in participants with ALSP in the Core Study	Week 24 and Week 52	Change from Baseline to Week 24 and Week 52 in soluble colony-stimulating factor 1 receptor (sCSF1R) in CSF
To evaluate the effects of iluzanebart on volumetric magnetic resonance imaging in participants with ALSP in the Core Study	Week 24 and Week 52	Change from Baseline to Week 24 and Week 52 in volumetric magnetic resonance imaging (MRI). The unit of this measure is ml.

Locations (10): Investigative Site 8
🇳🇱
Amsterdam, Netherlands
Investigative Site 7
🇩🇪
Leipzig, Germany
Investigative Site 3
🇺🇸
San Francisco, California, United States
Investigative Site 9
🇩🇪
Tübingen, Germany
Investigative Site 1
🇺🇸
Jacksonville, Florida, United States
Investigative Site 2
🇺🇸
Englewood, Colorado, United States
Investigative Site 5
🇺🇸
Boston, Massachusetts, United States
Investigative Site 6
🇺🇸
Philadelphia, Pennsylvania, United States
Investigative Site 10
🇫🇷
Paris, France
Investigative Site 4
🇬🇧
London, United Kingdom