Clinical trial NCT05677659: A Study of VGL101 in Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: ALSP
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
Lead sponsor: Vigil Neuroscience, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Core Study Adverse Events
timeFrame: Through Week 52
measure: Long-Term Extension Adverse Events
timeFrame: Week 52 through Week 148
Secondary outcomes:
measure: To evaluate the effects of iluzanebart on brain volume loss on MRI in subjects with ALSP in the Core Study
timeFrame: Baseline and Week 52
measure: To assess the correlation between brain volume loss on MRI and clinical measures of disease progression in subjects with ALSP in the Core Study
timeFrame: Baseline and Week 52
measure: To evaluate the effects of iluzanebart on clinical measures of disease progression in subjects with ALSP in the Core Study
timeFrame: Baseline and Week 52
measure: To evaluate the effects of iluzanebart on fluid biomarkers of neurodegeneration in subjects with ALSP in the Core Study
timeFrame: Baseline and Week 52
measure: To evaluate the pharmacokinetics of iluzanebart in subjects with ALSP in the Core Study
timeFrame: Through Week 52
measure: To evaluate the effects of iluzanebart on brain volume loss on MRI in subjects with ALSP in the Long-Term Extension
timeFrame: Baseline and Weeks 76, 100, 124, and 148
measure: 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
timeFrame: Baseline and Weeks 76, 100, 124, and 148
measure: To evaluate the effects of iluzanebart on clinical measures of disease progression in subjects with ALSP in the Long-Term Extension
timeFrame: Baseline and Weeks 64, 76, 88, 100, 112, 124, 136, and 148
measure: To evaluate the effects of iluzanebart on fluid biomarkers of neurodegeneration in subjects with ALSP in the Long-Term Extension
timeFrame: Baseline and Weeks 76, 100, 124, and 148
measure: To evaluate the pharmacokinetics of iluzanebart in subjects with ALSP in the Long-Term Extension
timeFrame: Week 52 through Week 148
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Investigative Site 3
state: California
city: Englewood
country: United States
facility: Investigative Site 2
state: Colorado
city: Jacksonville
country: United States
facility: Investigative Site 1
state: Florida
city: Boston
country: United States
facility: Investigative Site 5
state: Massachusetts
city: Philadelphia
country: United States
facility: Investigative Site 6
state: Pennsylvania
city: Paris
country: France
facility: Investigative Site 10
city: Leipzig
country: Germany
facility: Investigative Site 7
city: Tübingen
country: Germany
facility: Investigative Site 9
city: Amsterdam
country: Netherlands
facility: Investigative Site 8
city: London
country: United Kingdom
facility: Investigative Site 4
Study officials:
References: