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

Phase 2TerminatedNCT05677659

Vigil Neuroscience, Inc.20 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

ALSP

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (10)

Investigative Site 3

San Francisco, California, United States

Investigative Site 2

Englewood, Colorado, United States

Investigative Site 1

Jacksonville, Florida, United States

Investigative Site 5

Boston, Massachusetts, United States

Investigative Site 6

Philadelphia, Pennsylvania, United States

Investigative Site 10

Paris, France

Investigative Site 7

Leipzig, Germany

Investigative Site 9

Tübingen, Germany

Investigative Site 8

Amsterdam, Netherlands

Investigative Site 4

London, United Kingdom

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: Week 52 through Week 148

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Week 52 through Week 148