VGL101 to Treat Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia


About this study

The purpose of this study is to evaluate the safety and tolerability of VGL101 for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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:
  • The subject has > 2 findings of clinical signs or symptoms in the following categories:
  • Cognitive impairment or psychiatric problem.
  • Pyramidal signs on neurological examination.
  • Extrapyramidal signs, such as rigidity.
  • Epilepsy.
  • 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.
  • Note: Subjects who have other causes of leukoencephalopathy, including vascular dementia, multiple sclerosis, or leukodystrophy (eg, adrenoleukodystrophy, Krabbe disease, metachromatic leukodystrophy) will be excluded.
  • 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.
  • Sex and Contraceptive/Barrier Requirements
  • 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 VGL101.
  • The subject is capable of providing written informed consent, including signing and dating the ICF, or has a study partner or legal guardian who can provide written informed consent with subject assent. 
  • 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 VGL101 at the Baseline Visit.
  • The subject has a body mass index (BMI) between 17.5 and 38.0 kg/m^2 , 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 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 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.Note: A fundoscopic exam may be performed by qualified personnel prior to the lumbar puncture if imaging is not available to rule out risks for increased intracranial pressure.
  • 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.
  • 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. Note: Subjects who have not required active cancer treatment in the 3 years prior to Screening may qualify with Sponsor approval.
  • 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 VGL101 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 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.
  • Eligibility last updated 8/3/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Zbigniew Wszolek, M.D.

Open for enrollment

Contact information:

Audrey Strongosky C.C.R.C.

More information


Publications are currently not available

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