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TerminatedNCT05020743ALSPUpdated Aug 13, 2025Results posted

Natural History Study in Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

An observational study in ALSP, sponsored by Vigil Neuroscience, Inc.. Terminated at 12 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-13.

Sponsored by Vigil Neuroscience, Inc. (part of Sanofi) · Observational

Why this study was terminated
No beneficial effects on biomarker or clinical efficacy endpoints in the VGL101-01.201 Study
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
56
Ages
18 Years and older
Sex
All
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Study 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.

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Conditions studied

  • ALSP

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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
03

In context

Leukoencephalopathies

39 studies on the registry are indexed under Leukoencephalopathies; 16 are open to participants now.

This study's enrollment of 56 is below the median of 100 across 28 observational studies indexed under Leukoencephalopathies.

Browse Leukoencephalopathies studies →

Lead sponsor

Vigil Neuroscience, Inc. is the lead sponsor of 3 studies on the registry; none are open to participants now.

First submitted before Vigil Neuroscience, Inc. became part of Sanofi.

Browse Vigil Neuroscience, Inc. studies →All Sanofi studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Patients with Definitive ALSP and Prodromal ALSP.

Eligibility 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 or plan to undergo HSCT within 12 months of the Screening/Baseline visit.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
56 participants (actual)
Patient registry
No

Groups and cohorts

  • Patients with ALSP

    Other: No intervention

  • Patients with Prodromal ALSP

    Other: No intervention

Interventions

  • OtherNo intervention

    Not applicable for a Natural History Study

06

What researchers measure

Primary outcomes

  1. Magnetic Resonance Imaging (MRI) Ventricle Volume

    Change from Baseline in ventricle volume at Month 6

    Time frame: Month 6

  2. Magnetic Resonance Imaging (MRI) Ventricle Volume

    Change from Baseline in ventricle volume at Month 12

    Time frame: Month 12

  3. Magnetic Resonance Imaging (MRI) Ventricle Volume

    Change from Baseline in ventricle volume at Month 18

    Time frame: Month 18

  4. Magnetic Resonance Imaging (MRI) Ventricle Volume

    Change from Baseline in ventricle volume at Month 24

    Time frame: Month 24

  5. Magnetic Resonance Imaging (MRI) Ventricle Volume

    Change from Baseline in ventricle volume at Month 30

    Time frame: Month 30

07

Results

Posted Aug 13, 2025

Participant flow

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.

Participant flow — Overall Study
MilestoneProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Started192311
Completed600
Not completed132311
Withdrew: Enrollment in interventional study290
Withdrew: Withdrawal by subject031
Withdrew: Lost to follow-up100
Withdrew: Study termination by sponsor101110

Outcome measures

PrimaryMagnetic Resonance Imaging (MRI) Ventricle Volume

Change from Baseline in ventricle volume at Month 6

Time frame:
Month 6
Reported as:
Mean · cubic millimeter
Magnetic Resonance Imaging (MRI) Ventricle Volume
cubic millimeterProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Magnetic Resonance Imaging (MRI) Ventricle Volume498.3 ± 833.034153.2 ± 6052.353061.5 ± 5142.76
PrimaryMagnetic Resonance Imaging (MRI) Ventricle Volume

Change from Baseline in ventricle volume at Month 12

Time frame:
Month 12
Reported as:
Mean · cubic millimeter
Magnetic Resonance Imaging (MRI) Ventricle Volume
cubic millimeterProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Magnetic Resonance Imaging (MRI) Ventricle Volume1030.5 ± 1409.7610410.0 ± 7798.423565.6 ± 8930.46
PrimaryMagnetic Resonance Imaging (MRI) Ventricle Volume

Change from Baseline in ventricle volume at Month 18

Time frame:
Month 18
Reported as:
Mean · cubic millimeter
Magnetic Resonance Imaging (MRI) Ventricle Volume
cubic millimeterProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Magnetic Resonance Imaging (MRI) Ventricle Volume1236.9 ± 2139.0217758.8 ± 17376.195462.0 ± 6719.45
PrimaryMagnetic Resonance Imaging (MRI) Ventricle Volume

Change from Baseline in ventricle volume at Month 24

Time frame:
Month 24
Reported as:
Mean · cubic millimeter
Magnetic Resonance Imaging (MRI) Ventricle Volume
cubic millimeterProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Magnetic Resonance Imaging (MRI) Ventricle Volume1216.8 ± 2013.708901.6 ± NA5406.7 ± 5977.76
PrimaryMagnetic Resonance Imaging (MRI) Ventricle Volume

Change from Baseline in ventricle volume at Month 30

Time frame:
Month 30
Reported as:
Mean · cubic millimeter
Magnetic Resonance Imaging (MRI) Ventricle Volume
cubic millimeterProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Magnetic Resonance Imaging (MRI) Ventricle Volume1837.6 ± 2931.1713821.3 ± NA9115.2 ± 8421.27

Adverse events

Collected over From the time of signing the informed consent through up to 36 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Prodromal0/19 (0%)0/19 (0%)7/19 (36.8%)
Symptomatic/Definitive ALSP (no HSCT)0/23 (0%)2/23 (8.7%)6/23 (26.1%)
Symptomatic/Definitive ALSP (Prior HSCT)0/11 (0%)1/11 (9.1%)4/11 (36.4%)
Most frequent serious events
Most frequent serious events
EventProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Urinary tract infectionInfections and infestations0/190/231/11
Decubitus ulcerSkin and subcutaneous tissue disorders0/191/230/11
LeukoencephalopathyNervous system disorders0/191/230/11
Psychotic disorderPsychiatric disorders0/191/230/11
Most frequent other events
Showing 10 of 24
Most frequent other events
EventProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)
Bacterial infectionInfections and infestations0/190/231/11
Herpes virus infectionInfections and infestations0/190/231/11
InfectionInfections and infestations0/190/231/11
DepressionPsychiatric disorders0/190/231/11
InfluenzaInfections and infestations0/190/231/11
Uriinary tract infectionInfections and infestations0/190/231/11
Cervical spinal stenosisMusculoskeletal and connective tissue disorders0/190/231/11
CoughRespiratory, thoracic and mediastinal disorders0/190/231/11
PregnancyPregnancy, puerperium and perinatal conditions1/190/230/11
OsteoarthritisMusculoskeletal and connective tissue disorders1/190/230/11

Baseline characteristics

Age, Continuous
Age, Continuous(years)ProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)Total
Mean45.3 ± 16.6244.5 ± 11.5447.5 ± 4.5545.4 ± 12.54
Sex: Female, Male
Sex: Female, Male(Participants)ProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)Total
Female1215431
Male78722
Race (NIH/OMB)
Race (NIH/OMB)(Participants)ProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)Total
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American1304
White18191047
More than one race0101
Unknown or Not Reported0011
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)ProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)Total
Hispanic or Latino2619
Not Hispanic or Latino17161043
Unknown or Not Reported0101
Age at Diagnosis
Age at Diagnosis(years)ProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)Total
Mean45.0 ± 15.0043.6 ± 11.1843.9 ± 4.6044.0 ± 10.78
Duration Since Diagnosis
Duration Since Diagnosis(years)ProdromalSymptomatic/Definitive ALSP (no HSCT)Symptomatic/Definitive ALSP (Prior HSCT)Total
Mean1.1 ± 1.291.0 ± 1.404.1 ± 1.461.8 ± 1.92
08

Study locations

12 sites
  • Investigative Site 4
    San Francisco, California 94158, United States
  • Investigative Site 5
    Englewood, Colorado 80113, United States
  • Investigative Site 1
    Boca Raton, Florida 33486, United States
  • Investigative Site 2
    Jacksonville, Florida 32224, United States
  • Investigative Site 11
    Boston, Massachusetts 02114, United States
  • Investigative Site 10
    Philadelphia, Pennsylvania 19104, United States
  • Investigative Site 12
    São Paulo, 04038, Brazil
  • Investigative Site 3
    London, Ontario N6C 5J1, Canada
  • Investigative Site 8
    Leipzig, 04103, Germany
  • Investigative Site 9
    Tübingen, 72076, Germany
  • Investigative Site 6
    Amsterdam, 1105 AZ, Netherlands
  • Investigative Site 7
    London, WC1N 3BG, United Kingdom
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 13, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05020743
Lead sponsor
Vigil Neuroscience, Inc.
Responsible party
Sponsor
First posted
Aug 25, 2021
Start date
Sep 13, 2021
Primary completion
May 30, 2025
Completion
May 30, 2025
Results posted
Aug 13, 2025
Last update
Aug 13, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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