ALSP
Conditions
Keywords
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
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.
Interventions
DRUGVGL101
Solution administered via Intravenous Infusion (IV)
Sponsors
Vigil Neuroscience, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-Term Extension Adverse Events | Week 52 through Week 148 | To evaluate the safety and tolerability of iluzanebart for the treatment of ALSP by adverse events in the Long-Term Extension |
| Core Study Adverse Events | Through 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effects of iluzanebart on clinical measures of disease progression in subjects with ALSP in the Core Study | Baseline and Week 52 | * 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 |
| To evaluate the effects of iluzanebart on fluid biomarkers of neurodegeneration in subjects with ALSP in the Core Study | Baseline and Week 52 | Change from Baseline to Week 52 in neurofilament light chain (NfL) in and blood |
| To evaluate the pharmacokinetics of iluzanebart in subjects with ALSP in the Core Study | Through Week 52 | Serum and cerebrospinal fluid (CSF) concentrations of iluzanebart |
| To evaluate the effects of iluzanebart on brain volume loss on MRI in subjects with ALSP in the Long-Term Extension | Baseline and Weeks 76, 100, 124, and 148 | Change from Baseline to Weeks 76, 100, 124, and 148 in brain volume loss |
| To evaluate the effects of iluzanebart on brain volume loss on MRI in subjects with ALSP in the Core Study | Baseline and Week 52 | Percentage of subjects with minimal radiological progression from Baseline to Week 52 |
| To evaluate the effects of iluzanebart on clinical measures of disease progression in subjects with ALSP in the Long-Term Extension | Baseline and Weeks 64, 76, 88, 100, 112, 124, 136, and 148 | * 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 |
| To evaluate the effects of iluzanebart on fluid biomarkers of neurodegeneration in subjects with ALSP in the Long-Term Extension | Baseline and Weeks 76, 100, 124, and 148 | Change from Baseline to Weeks 76, 100, 124, and 148 in NfL in blood |
| To evaluate the pharmacokinetics of iluzanebart in subjects with ALSP in the Long-Term Extension | Week 52 through Week 148 | Serum and CSF concentrations of iluzanebart |
| 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 | Baseline and Weeks 76, 100, 124, and 148 | * 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 |
| To assess the correlation between brain volume loss on MRI and clinical measures of disease progression in subjects with ALSP in the Core Study | Baseline and Week 52 | * 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 |
Countries
France, Germany, Netherlands, United Kingdom, United States
Outcome results
None listed