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)
- Trial ID
- 2022-502505-15-00
- Protocol
- VGL101-01.201
- Sponsor
- Vigil Neuroscience Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and **tolerability** of iluzanebart for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). This is clinically relevant as it aims to ensure that the treatment is safe for patients and can be tolerated over the course of therapy, which is crucial for the management of this progressive neurological disorder.
Secondary objectives include:
- To evaluate the effects of iluzanebart on imaging and biomarkers of disease progression in subjects with ALSP.
Participants
The clinical trial involves a total of **11 participants** diagnosed with **leukoencephalopathy**, specifically adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). The study population includes both male and female subjects aged 18 years and older. Participants are required to be ambulatory, with or without aids, or capable of self-mobility if using a wheelchair. The trial population was selected based on specific inclusion criteria, including the presence of a gene mutation in the CSF1R gene and clinical or radiological progression of ALSP within the past year. Participants must have a body mass index (BMI) between 17.5 and 38.0 kg/m² and meet local COVID-19 testing guidelines. Lifestyle considerations such as the use of effective contraception for sexually active individuals and the ability to refrain from prohibited medications during the study are also required. The trial includes a vulnerable population, and participants must have a study partner to assist with compliance if cognitive or mental impairments are present. The sponsor has not provided additional information regarding the general health status or specific lifestyle habits of the participants.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and tolerability of VGL101, a **solution for injection**, in patients with adult-onset **leukoencephalopathy** with axonal spheroids and pigmented glia (ALSP). This is a Phase 2, randomized, double-blind, controlled study. The trial is expected to last until January 2027, with participant involvement spanning up to 52 weeks. The study will include a series of visits, starting with a screening visit to assess eligibility based on criteria such as age, ambulatory status, cognitive function, and genetic markers. Participants will be required to provide informed consent, and women of childbearing potential must have a negative pregnancy test before enrollment.
Following the screening, eligible participants will undergo a baseline visit where initial assessments, including MRI and laboratory tests, will be conducted. The investigational product, VGL101, will be administered via **intravenous infusion**. Participants will attend regular follow-up visits to monitor safety and efficacy, with assessments including adverse event reporting, laboratory tests, and imaging studies. The primary endpoint focuses on the nature and frequency of adverse events, while secondary endpoints include changes in MRI findings and biomarker levels.
The end-of-study visit will occur at the conclusion of the 52-week treatment period, where final assessments will be conducted to evaluate the long-term effects of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study requirements, or if the investigator deems it necessary for their safety. The study aims to provide valuable insights into the potential therapeutic benefits of VGL101 for individuals affected by ALSP.
Treatment
The clinical trial involves the administration of **VGL101**, an experimental medication developed by Vigil Neuroscience, Inc. **VGL101** is a **solution for injection** designed for intravenous infusion. The active substance, also named **VGL101**, is a protein of other origin. The pharmaceutical form of the medication is a solution for injection, and it is classified as a biological product. The dosing regimen for **VGL101** is set at a maximum daily dose of 40 mg/kg, with the same maximum total dose amount. The treatment period is capped at 52 weeks. The administration route is through intravenous infusion, ensuring direct delivery into the bloodstream. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus remains solely on evaluating the safety, tolerability, and proof-of-concept of **VGL101** in patients diagnosed with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). The trial aims to gather data on the effects of **VGL101** over the specified treatment period, with careful monitoring of participant responses and any adverse events.
Efficacy
Efficacy in the clinical trial of VGL101 for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) will be assessed using both primary and secondary endpoints. The primary endpoints focus on safety and tolerability, evaluated through the nature and frequency of adverse events, serious adverse events, and discontinuations due to adverse events. Additional safety assessments include laboratory tests, immunogenicity tests, vital sign measurements, electrocardiograms, and the Columbia-Suicide Severity Rating Scale (C-SSRS).
Secondary endpoints will measure changes from baseline to Week 24 and Week 52 in structural and volumetric magnetic resonance imaging (MRI). Biomarker levels, specifically neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and blood, will be assessed at Week 24 and Week 52. Changes in soluble colony-stimulating factor 1 receptor (sCSF1R) in CSF will also be evaluated. Correlations between biomarker changes and clinical outcomes at Week 24 and Week 52 will be analyzed to further assess efficacy. These assessments will provide comprehensive data on the efficacy of VGL101 in treating ALSP.
Inclusion and Exclusion Criteria
Inclusion Criteria
- The subject is of either sex aged ≥18 years on the day the informed consent form (ICF) is signed.
- The subject is, in the investigator’s judgment, able to understand the nature of the study and to comply with the protocol requirements, including scheduled visits, blood and CSF sampling, and other study procedures, or has a study partner or legal guardian who can understand and assist the subject in complying with the protocol requirements for the duration of the study.
- The subject is willing and able to refrain from use of any medications or treatments that are not permitted by the protocol throughout the study period.
- The subject has received the approval of Sponsor medical personnel as to final suitability for the study.
- The subject has documentation of a gene mutation in the CSF1R gene before enrollment into the study. Historical documentation is sufficient to support eligibility for the study; a blood sample for confirmatory testing will be obtained at Baseline.
- The subject fulfills both (Parts a and b) of the following criteria: a. The subject has >2 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. iv. Epilepsy. b. MRI findings consistent with ALSP (Konno, 2018; Appendix 5), specifically, bilateral cerebral white matter lesions with or without thinning of the corpus callosum, on the Screening MRI.
- The subject has, in the investigator’s opinion, demonstrated clinical and/or radiological progression of ALSP within the past year.
- The subject has a total score of ≥14 on the Montreal Cognitive Assessment (MoCA).
- The subject is in stable condition in the opinion of the investigator.
- The subject is ambulatory with or without aids (cane, crutches, etc) or, if restricted to a wheelchair, can wheel himself/herself, transfer in and out of the wheelchair, and walk up to 5 meters with or without aid. Subjects who are not ambulatory may be eligible after consultation with the medical monitor.
- If the subject has a cognitive or mental impairment that can affect his/her ability to comply with the study requirements, the subject has a designated study partner. The study partner is able and willing to assist the subject in complying with the study requirements, can provide information during study visits, and is willing to sign a study partner ICF.
- The subject must have a study partner (ie, 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 subject’s health and cognitive and functional abilities. The study partner must be willing to sign a study partner ICF.
- If a sexually active women of childbearing potential (ie, women who have not achieved postmenopausal status, defined as cessation of regular menses for ≥12 consecutive months with no alternative pathological or physiological cause, and have a serum follicle-stimulating hormone [FSH] level confirming the postmenopausal state) or who have not undergone a documented hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or a man who has not been surgically sterilized by vasectomy, the subject agrees to use effective contraception during the study and for at least 3 months after the last dose of iluzanebart.
- The subject must provide written informed consent, including signing and dating the ICF prior to inclusion in the study, or have a study partner or legal guardian who provides written informed consent with subject assent prior to inclusion in the study if they are unable to provide their own informed consent.
- If a woman of childbearing potential, the subject has a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test within 24 hours before administration of the first dose of iluzanebart at the Baseline Visit.
- The subject has a body mass index (BMI) between 17.5 and 38.0 kg/m2, inclusive, at the Screening Visit.
- The subject meets local guidelines related to COVID-19 testing before the Screening Visit.
Exclusion Criteria
- The subject has any neurological disease that poses a risk to the subject 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.
- The subject is at significant risk of suicidal or violent behavior, in the opinion of the investigator. If a subject answers “yes” to 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.
- The subject has a current history of any major or unstable medical illness, including, but not limited to, renal failure, congestive heart failure, uncontrolled diabetes mellitus, or advanced pulmonary disease, that could, in the opinion of the investigator, pose a risk to the subject during the study.
- The subject has clinically significant abnormalities in vital signs, ECG, or laboratory parameters at Screening, which, in the opinion of the investigator, would pose a risk to the subject.
- The subject has a history of cancer that required active treatment in the 5 years prior to Screening, with the exception of in situ cervical cancer or basal cell carcinoma of the skin.
- The subject has a history of or known infection with human immunodeficiency virus (HIV) or hepatitis B or C (testing upon investigator assessment of risk factor).
- The subject lacks adequate venous access to allow for study procedures (IV administration of iluzanebart or blood sampling).
- The subject has a history of hypersensitivity to the study drug, other therapeutic monoclonal antibodies, or any of the excipients or to medicinal products with similar chemical structures.
- The subject has 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.
- The subject has undergone HSCT or is planning to undergo HSCT during the conduct of this study.
- The subject is currently enrolled in another investigational drug or device study or has received an investigational product within 30 days or 5 half-lives prior to Screening for this study.
- The subject has a significant Axis I psychiatric disease as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (American Psychiatric Association, 2013) that in the opinion of the investigator could pose a risk to the subject or interfere with participation in the study. Presence of minor depression or treated, stable depressive disorder is acceptable.
- The subject has previously participated in a gene therapy study.
- The subject is involved, directly or indirectly, in the conduct or administration of this study as an investigator, sub-investigator, study coordinator, or other study staff member.
- The subject has a clinically significant alcohol or substance use disorder (other than caffeine or nicotine) as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (American Psychiatric Association, 2013) within 1 year before Screening.
- The subject has any concurrent diagnosis that may confound neuropsychological testing (eg, hearing impairment, visual impairment) in the opinion of the investigator.
- The subject has any concurrent diagnosis that may confound ambulation measurements (eg, amputee) in the opinion of the investigator.
- The subject has a hypersensitivity to anesthetic or derivatives that are used during CSF collection, a history of vertebral deformities, major lumbar back surgery, clinically significant back pain, clinically significant abnormal X-ray, ongoing skin infection or injury at the lumbar puncture injection site, radiological indication of increased intracranial pressure, or a bleeding disorder that, in the opinion of the investigator, would expose the subject to risk of injury or unsuccessful lumbar puncture.
- The subject is unable to undergo MRI (eg, has implants not compatible for MRI, claustrophobia, is unable to remain still so that a good quality scan can be obtained). Subjects who have renal impairment or contraindications for use of MRI may be enrolled. Contrast MRI scans should not be performed in these subjects; noncontrast scans are required
- The subject has brain MRI findings, at Screening, of acute or subacute hemorrhage, macrohemorrhage, >4 microhemorrhages, or ≥1 superficial siderosis or other clinically significant imaging abnormalities, including, but not limited to, arteriovenous malformation, aneurism, and subdural hematoma that, in the opinion of the investigator, would pose a risk to the subject.
- The subject is female and is pregnant, planning pregnancy in the next 12 months, or breastfeeding.
- All groups of persons requiring special protection according to Sec. 136 and 137 StrlSchV will be explicitly excluded from study participation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 01 Aug 2023 | 3 |
 Germany | Not Recruiting | 01 Aug 2023 | 3 |
 The Netherlands | Not Recruiting | 01 Aug 2023 | — |
| Netherlands | — | — | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
VGL101 | Test | SOLUTION FOR INJECTION | INTRAVENIOUS INFUSION | 40 | 52 | PRD10259270 |