ALSP
Conditions
Interventions
None listed
Sponsors
Vigil Neuroscience, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: General and Administrative 1. Male or female subjects aged >=18 years on the day the informed consent form (ICF) is signed. 2. Subjects who are able, in the opinion of the investigator, to understand the nature of the study and to comply with the protocol requirements, including scheduled visits, blood sampling, and other study procedures, or who have a caregiver or legal guardian who can understand and assist the subject in complying with the protocol requirements. 3. Subjects who are willing and able to refrain from use of any prohibited medication/treatments that are not permitted by the protocol throughout the study period. 4. Subjects who receive approval of sponsor medical personnel as to final suitability for the study. Inclusion Criteria - Subjects With Definitive ALSP 5. Subjects who have documentation of a gene mutation in the CSF1R gene (prior to enrollment). 6. Subjects who fulfill both of the following criteria (a and b): a. More than two findings of clinical signs or symptoms in any of 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: specially, bilateral cerebral white matter lesions with or without thinning of the corpus callosum (Konno et al, 2018; Appendix 3, Section 10.3). NOTE: Subjects with other causes of leukoencephalopathy, including vascular dementia, multiple sclerosis, or leukodystrophy (e.g., adrenoleukodystrophy, Krabbe disease, metachromatic leukodystrophy), will be excluded. 7. Subjects who, in the investigator*s opinion, have demonstrated clinical progression of their ALSP within the past year. 8. Subjects who have a score of >=12 on the MoCA. 9. Subjects who are ambulatory with or without aids (cane, crutches, etc) or, if restricted to a wheelchair, are still able to wheel self, transfer in and out of wheelchair, and walk up to 5 meters with or without aid. NOTE: 7 subjects that are non-ambulatory for reasons other than progression of ALSP may be enrolled. 10. Subjects who meet the criteria for definitive ALSP must have a designated caregiver who spends at least 4 hours per week with them. The caregiver 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 caregiver ICF. Inclusion Criteria - Subjects With Prodromal ALSP 11. Subjects who have documentation of a gene mutation in CSF1R gene (prior to enrollment). 12. MRI findings consistent with ALSP: specifically, bilateral cerebral white matter lesions with or without thinning of the corpus callosum (Konno et al, 2018; Appendix 3, Section 10.3). Prodromal subjects may have none or up to and including 2 ALSP-related clinical signs or symptoms (i.e., they do not meet the clinical criteria outlined in 6a as *more than two*). 13. Subjects who meet the criteria for prodromal ALSP and who, at later study visits, meet the criteria for definitive ALSP should have a designated caregiver for subsequent visits who spends at least 4 hours per week with them unless otherwise approved by the sponsor and/or medical monitor. The careg
Exclusion criteria
Exclusion criteria: Medical Conditions 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 with any concurrent diagnosis that may confound neuropsychological testing (e.g., hearing impairment, visual impairment). 3. Subjects with any concurrent diagnosis that may confound ambulation measurements (e.g., amputee). 4. Subjects with contraindications for undergoing a lumbar puncture, such as bleeding disorders, increased intracranial pressure, or abnormal spinal anatomy. NOTE: Only for subjects who participate in the optional CSF Biomarker Sub-study. 5. Subjects who are unable to undergo MRI. (e.g., implants not compatible for MRI, claustrophobia, inability to remain still that will prevent acquisition of a good quality scan) 6. Female subjects who are pregnant, planning pregnancy in the next 12 months, or breastfeeding. 7. Subjects who are at significant risk of suicidal or violent behavior, in the opinion of the investigator. If a subject answers *yes* to the Question 4 or 5 on the C SSRS, a risk assessment should be done by a qualified healthcare professional to assess whether it is safe for the subject to participate in the study. 8. Subjects with a current history of major medical illness, such as renal failure, congestive heart failure, or advanced pulmonary disease, that could put the subject at additional risk if participating in the study. 9. Subjects with a history of cancer that required active treatment in the last 5 years, with the exception of in situ cervical cancer and basal cell carcinoma of the skin. 10. 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. 11. Subjects who have previously undergone HSCT or plan to undergo HSCT within 12 months prior to Screening/Baseline visit. Prior/Current Clinical Study Experience 12. Subjects who are concurrently enrolled in an investigational drug or device study or who received an investigational product within 30 days of 5 half-lives before signing the ICF. Note: Subjects who are receiving VGL101 in a clinical study may enroll after conclusion of their participation in the VGL101 clinical study Other Exclusion Criteria 13. Subjects who are involved, directly or indirectly, in the conduct or administration of this study as an investigator, sub-investigator, study coordinator, or other study staff member.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacodynamic Endpoints • Change from Baseline to Months 12, 24 and 36 in neurofilament light chain (NfL) in blood • Change from Baseline to Months 12, 24 and 36 in NfL, cytokine panel, soluble TREM2, and soluble CSF1R in CSF in subjects who provide informed consent to participate in an optional CSF Biomarker Sub-study • Change from Baseline to Months 6, 12, 18, 24, 30, 36 in structural and volumetric MRI Clinical Outcome Endpoints Cognitive Assessments • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Montreal Cognitive Assessment (MoCA) • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Clinical Dementia Rating Scale plus National Alzheimer*s Coordinating Center- Frontotemporal Lobar Degeneration (CDR®+NACC FTLD) • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Brief Assessment of Cognition (BAC) battery. Motor Assessments (Ambulatory Subjects) • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the 2 Minute Walk Test (2MWT) • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Timed Up and Go (TUG) test Severity of Illness Assessments • Clinical Global Impression - Change (CGI C) responses at Months 6, 12, 18, 24, 30 and 36 • Clinical Global Impression - Change (PGI C) responses at Months 6, 12, 18, 24, 30 and 36 Other Functional and Psychiatric Assessments • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Functional Activities Questionnaire (FAQ) • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Neuropsychiatric Inventory - 12-Item Version (NPI-12) • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Cortical Basal ganglia Functional Scale (CBFS) • Change from Baseline to Months 6, 12, 18, 24, 30 and 36 in the Zarit Burden Interview Safety Endpoints • Adverse events (AEs) • Columbia-Suicide Severity Rating Scale (C-SSRS) | — |
Secondary
| Measure | Time frame |
|---|---|
| . | — |
Countries
Netherlands
Outcome results
None listed