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

Study Overview
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Brief Summary
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This is a multicenter, open-label study to assess the safety and tolerability of 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 VGL101 on imaging and biomarkers of disease progression in subjects with ALSP. Participants will receive infusions of VGL101 approximately every 4 weeks for 1 year.

Official Title
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A Phase 2 Safety, Tolerability, and Proof-of-Concept Study of VGL101 in Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia (ALSP) (The Ignite Study)

Conditions
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ALSP

Intervention / Treatment
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* Drug: VGL101


Participation Criteria
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Eligibility Criteria
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Key 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: The participant has more than 2 findings of clinical signs or symptoms in the following categories: Cognitive impairment or psychiatric problem Pyramidal signs on neurological examination Extrapyramidal signs, such as rigidity. Epilepsy 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VGL101<br>Solution administered via Intravenous Infusion (IV) | Drug: VGL101<br>* Solution administered via Intravenous Infusion (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | To evaluate the safety and tolerability of VGL101 for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) by adverse events | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of VGL101 on volumetric magnetic resonance imaging in participants with ALSP | Change from Baseline to Week 24 in volumetric magnetic resonance imaging (MRI). The unit of this measure is ml. | Week 24 | 
| To evaluate the effects of VGL101 on in the ALSP severity score based on MRI in participants with ALSP | Change from Baseline to Week 24 in the ALSP severity score based on MRI. The scale has a minimum score of 0 and maximum score of 57. Higher scores represent greater radiographical disease burden. | Week 24 | 
| To evaluate the effects of VGL101 on biomarkers of disease progression in participants with ALSP | Change from Baseline to Week 24 in neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and blood | Week 24 | 
| To evaluate the effects of VGL101 on biomarkers of target engagement in participants with ALSP | Change from Baseline to Week 24 in soluble colony-stimulating factor 1 receptor (sCSF1R) in CSF | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALSP, CSF1R, leukoencephalopathy, Hereditary Diffuse Leukoencephalopathy with Spheroids, HDLS, CSF1R-related Leukoencephalopathy, Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia, CSF1R gene mutation, IGNITE