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

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)

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.

Study Overview

• Status: Terminated
• Conditions: ALSP
• Intervention / Treatment: Drug: VGL101

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Investigative Site 10
• Germany
  • Leipzig, Germany
    • Investigative Site 7
  • Tübingen, Germany
    • Investigative Site 9
• Netherlands
  • Amsterdam, Netherlands
    • Investigative Site 8
• United Kingdom
  • London, United Kingdom
    • Investigative Site 4
• United States
  • California
    • San Francisco, California, United States, 94158
      • Investigative Site 3
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Investigative Site 2
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Investigative Site 1
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Investigative Site 5
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Investigative Site 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

  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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VGL101; Solution administered via Intravenous Infusion (IV)	Drug: VGL101; Solution administered via Intravenous Infusion (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Study Adverse Events	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	Through Week 52
Long-Term Extension Adverse Events	To evaluate the safety and tolerability of iluzanebart for the treatment of ALSP by adverse events in the Long-Term Extension	Week 52 through Week 148

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effects of iluzanebart on brain volume loss on MRI in subjects with ALSP in the Core Study	Percentage of subjects with minimal radiological progression from Baseline to Week 52	Baseline and Week 52
To assess the correlation between brain volume loss on MRI and clinical measures of disease progression in subjects with ALSP in the Core Study	Correlation between brain volume loss and Montreal Cognitive Assessment (MoCA) changes from Baseline to Week 52; Correlation between brain volume loss and Cortical basal ganglia functional scale (CBFS) changes from Baseline to Week 52	Baseline and Week 52
To evaluate the effects of iluzanebart on clinical measures of disease progression in subjects with ALSP in the Core Study	Percentage of subjects with minimal progression in the MoCA scale, from Baseline to Week 52; Percentage of subjects with minimal progression in CBFS from Baseline to Week 52; Percentage of subjects who did not worsen in the Clinical Global Impression - Change (CGI-C) scale at Week 52	Baseline and Week 52
To evaluate the effects of iluzanebart on fluid biomarkers of neurodegeneration in subjects with ALSP in the Core Study	Change from Baseline to Week 52 in neurofilament light chain (NfL) in and blood	Baseline and Week 52
To evaluate the pharmacokinetics of iluzanebart in subjects with ALSP in the Core Study	Serum and cerebrospinal fluid (CSF) concentrations of iluzanebart	Through Week 52
To evaluate the effects of iluzanebart on brain volume loss on MRI in subjects with ALSP in the Long-Term Extension	Change from Baseline to Weeks 76, 100, 124, and 148 in brain volume loss	Baseline and Weeks 76, 100, 124, and 148
To assess the correlation between brain volume loss on MRI and clinical measures of disease progression in subjects with ALSP in the Long-Term Extension	Correlation between brain volume loss and MoCA changes from Baseline to Weeks 76, 100, 124, and 148; Correlation between brain volume loss and CBFS changes from Baseline to Weeks 76, 100, 124, and 148	Baseline and Weeks 76, 100, 124, and 148
To evaluate the effects of iluzanebart on clinical measures of disease progression in subjects with ALSP in the Long-Term Extension	Change from baseline to Weeks 64, 76, 88, 100, 112, 124, 136, and 148 in the MoCA and CBFS; Mean CGI-C score at Weeks 64, 76, 88, 100, 112, 124, 136, and 148	Baseline and Weeks 64, 76, 88, 100, 112, 124, 136, and 148
To evaluate the effects of iluzanebart on fluid biomarkers of neurodegeneration in subjects with ALSP in the Long-Term Extension	Change from Baseline to Weeks 76, 100, 124, and 148 in NfL in blood	Baseline and Weeks 76, 100, 124, and 148
To evaluate the pharmacokinetics of iluzanebart in subjects with ALSP in the Long-Term Extension	Serum and CSF concentrations of iluzanebart	Week 52 through Week 148

Collaborators and Investigators

• Sponsor: Vigil Neuroscience, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2022
• Primary Completion (Actual): February 14, 2025
• Study Completion (Actual): June 4, 2025

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Actual): January 10, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: CSF1R; HDLS; leukoencephalopathy; ALSP; Hereditary Diffuse Leukoencephalopathy with Spheroids; CSF1R-related Leukoencephalopathy; Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia; CSF1R gene mutation; IGNITE
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies
• Other Study ID Numbers: VGL101-01.201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No