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, POLD, Pigmentary Orthochromatic Leukodystrophy
Brief summary
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, rapidly progressing, genetic, neurodegenerative disease for which no definitive treatment options and limited information on the natural history of the disease are available. The structural, genetic, and neuropathophysiological abnormalities of ALSP lead to the onset of neurologic symptoms, such as moderate to severe motor and neuropsychiatric impairments. This natural history study will collect data to contribute to the development of future novel therapies that focus on the neuropathophysiological features that underlie ALSP and that are essential to reverse, delay, or stop progression of this debilitating disorder.
Interventions
OTHERNo intervention
Not applicable for a Natural History Study
Sponsors
Vigil Neuroscience, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria for Definitive ALSP patients: 1. Subjects who have documentation of a gene mutation in the CSF1R gene (prior to enrollment) 2. Subjects who fulfill both of the following criteria (a and b): a. More than two findings of clinical signs or symptoms in the following categories: i. Cognitive impairment or psychiatric problem ii. Pyramidal signs on neurological examination iii. Extrapyramidal signs, such as rigidity, tremor, abnormal gait, or bradykinesia iv. Epilepsy b. MRI findings consistent with ALSP: specifically, bilateral cerebral white matter lesions with or without thinning of the corpus callosum NOTE: Subjects with other causes of leukoencephalopathy, including vascular dementia, multiple sclerosis, or leukodystrophy (e.g., adrenoleukodystrophy, Krabbe disease, metachromatic leukodystrophy), will be excluded. 3. Subjects who, in the investigator's opinion, have demonstrated clinical progression of their ALSP within the past year. 4. Subjects who meet the criteria for definitive ALSP must have a designated study partner (i.e caregiver) who spends at least 4 hours per week with them. The study partner must be able and willing to assist the subject in complying with the study requirements, be able to provide information during study visits, and be willing to sign a study partner ICF. Subjects who do not have a study partner may be enrolled at the investigator's discretion if they are able to comply with protocol requirements. Key
Exclusion criteria
for Definitive ALSP patients: 1. Subjects with any neurological or psychiatric diseases that can produce cognitive, motor, or behavioral impairment similar to ALSP, including, but not limited to, Alzheimer's disease, frontotemporal dementia, ALS, stroke, Huntington disease, multiple sclerosis, Parkinson's disease, and Down syndrome, or with active alcohol/drug abuse 2. Subjects who are unable to undergo MRI 3. Subjects 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 subject's participation in the study. 4. Subjects who have previously undergone HSCT or plan to undergo HSCT within 12 months of the Screening/Baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Magnetic Resonance Imaging (MRI) Ventricle Volume | Month 6 | Change from Baseline in ventricle volume at Month 6 |
Countries
Brazil, Canada, Germany, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 11 sites that screened participants in the United States, Canada, Netherlands, United Kingdom, Germany, and Brazil. The first participant was enrolled on September 13, 2021 and the last participant was enrolled on April 23, 2025.
Pre-assignment details
Of 82 screened patients, 26 failed to meet eligibility criteria. Of 56 participants enrolled in the study, 53 were enrolled prior to the data cutoff of February 19, 2025.
Participants by arm
| Arm | Count |
|---|---|
| Prodromal ALSP participants with confirmed CSF1R mutation, radiographic evidence of ALSP, and who had none or up to and including 2 ALSP-related clinical signs or symptoms. | 19 |
| Symptomatic/Definitive ALSP (no HSCT) ALSP participants with confirmed CSF1R mutation, radiographic evidence of ALSP and had at least 3 ALSP-related clinical signs or symptoms, and did not have hematopoietic stem cell transplant (HSCT) procedure. | 23 |
| Symptomatic/Definitive ALSP (Prior HSCT) ALSP participants with CSF1R mutation, radiographic evidence of ALSP and had at least 3 ALSP-related clinical signs or symptoms, and had prior hematopoietic stem cell transplant (HSCT) procedure. | 11 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Enrollment in Interventional Study | 2 | 9 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Study Termination by Sponsor | 10 | 11 | 10 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | Prodromal | Total | Symptomatic/Definitive ALSP (no HSCT) | Symptomatic/Definitive ALSP (Prior HSCT) |
|---|---|---|---|---|
| Age at Diagnosis | 45.0 years STANDARD_DEVIATION 15 | 44.0 years STANDARD_DEVIATION 10.78 | 43.6 years STANDARD_DEVIATION 11.18 | 43.9 years STANDARD_DEVIATION 4.6 |
| Age, Continuous | 45.3 years STANDARD_DEVIATION 16.62 | 45.4 years STANDARD_DEVIATION 12.54 | 44.5 years STANDARD_DEVIATION 11.54 | 47.5 years STANDARD_DEVIATION 4.55 |
| Duration Since Diagnosis | 1.1 years STANDARD_DEVIATION 1.29 | 1.8 years STANDARD_DEVIATION 1.92 | 1.0 years STANDARD_DEVIATION 1.4 | 4.1 years STANDARD_DEVIATION 1.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 9 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 43 Participants | 16 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 47 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Female | 12 Participants | 31 Participants | 15 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 22 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 23 | 0 / 11 |
| other Total, other adverse events | 7 / 19 | 6 / 23 | 4 / 11 |
| serious Total, serious adverse events | 0 / 19 | 2 / 23 | 1 / 11 |
Outcome results
Primary
Magnetic Resonance Imaging (MRI) Ventricle Volume
Change from Baseline in ventricle volume at Month 6
Time frame: Month 6
Population: Not all participants completed Month 6 visit prior to data cutoff.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prodromal | Magnetic Resonance Imaging (MRI) Ventricle Volume | 498.3 cubic millimeter | Standard Deviation 833.03 |
| Symptomatic/Definitive ALSP (no HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 4153.2 cubic millimeter | Standard Deviation 6052.35 |
| Symptomatic/Definitive ALSP (Prior HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 3061.5 cubic millimeter | Standard Deviation 5142.76 |
Primary
Magnetic Resonance Imaging (MRI) Ventricle Volume
Change from Baseline in ventricle volume at Month 12
Time frame: Month 12
Population: Not all participants completed Month 12 visit prior to data cutoff.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prodromal | Magnetic Resonance Imaging (MRI) Ventricle Volume | 1030.5 cubic millimeter | Standard Deviation 1409.76 |
| Symptomatic/Definitive ALSP (no HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 10410.0 cubic millimeter | Standard Deviation 7798.42 |
| Symptomatic/Definitive ALSP (Prior HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 3565.6 cubic millimeter | Standard Deviation 8930.46 |
Primary
Magnetic Resonance Imaging (MRI) Ventricle Volume
Change from Baseline in ventricle volume at Month 18
Time frame: Month 18
Population: Not all participants completed Month 18 visit prior to data cutoff.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prodromal | Magnetic Resonance Imaging (MRI) Ventricle Volume | 1236.9 cubic millimeter | Standard Deviation 2139.02 |
| Symptomatic/Definitive ALSP (no HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 17758.8 cubic millimeter | Standard Deviation 17376.19 |
| Symptomatic/Definitive ALSP (Prior HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 5462.0 cubic millimeter | Standard Deviation 6719.45 |
Primary
Magnetic Resonance Imaging (MRI) Ventricle Volume
Change from Baseline in ventricle volume at Month 24
Time frame: Month 24
Population: Not all participants completed Month 24 visit prior to data cutoff.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prodromal | Magnetic Resonance Imaging (MRI) Ventricle Volume | 1216.8 cubic millimeter | Standard Deviation 2013.7 |
| Symptomatic/Definitive ALSP (no HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 8901.6 cubic millimeter | — |
| Symptomatic/Definitive ALSP (Prior HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 5406.7 cubic millimeter | Standard Deviation 5977.76 |
Primary
Magnetic Resonance Imaging (MRI) Ventricle Volume
Change from Baseline in ventricle volume at Month 30
Time frame: Month 30
Population: Not all participants completed Month 30 visit prior to data cutoff.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prodromal | Magnetic Resonance Imaging (MRI) Ventricle Volume | 1837.6 cubic millimeter | Standard Deviation 2931.17 |
| Symptomatic/Definitive ALSP (no HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 13821.3 cubic millimeter | — |
| Symptomatic/Definitive ALSP (Prior HSCT) | Magnetic Resonance Imaging (MRI) Ventricle Volume | 9115.2 cubic millimeter | Standard Deviation 8421.27 |