A Phase 2 interventional study of Brincidofovir in Progressive Multifocal Leukoencephalopathy, sponsored by National Institute of Neurological Disorders and Stroke (NINDS). Recruiting at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-07-22.
Sponsored by National Institute of Neurological Disorders and Stroke (NINDS) · Phase 2, Interventional, and Treatment
Background:
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal brain infection caused by the JC virus. The JC virus is common. More than half of adults have been exposed to it. Most people do not get sick from the JC virus, but in people with weakened immune systems, it can cause PML. Brincidofovir (BCV) is an antiviral drug approved to treat smallpox. Researchers want to know if it can help people with PML.
Objective:
To test BCV in people with PML.
Eligibility:
People aged 18 years or older with PML.
Design:
Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan of the brain with contrast dye. They will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord.
BCV will be given through a tube attached to a needle inserted into a vein. Participants will receive the drug 2 times a week for 4 weeks (this is 1 cycle). If the drug is helping them, they may have up to 3 drug cycles (12 weeks).
Imaging scans, spinal taps, and other tests will be repeated after every 4 weeks of treatment. Participants will have 6 follow-up visits in 1 year after treatment ends. The imaging scan, spinal tap, and other tests will be repeated at each visit.
Study Description:
This pilot study will test safety and tolerability of IV BCV as an antiviral treatment strategy for participants with PML, and will collect preliminary data on biological and clinical impact on PML disease course. Eighteen adults with PML from all causes will complete this study.
Following a standardized baseline evaluation and confirmation of PML diagnosis with positive JCPyV DNA detection in CSF, participants will receive IV BCV 20mg (or 0.4mg/kg if participant weighs\<50kg) twice weekly in 4-week Infusion Cycles for up to 12 weeks total (3 Infusion Cycles).
At completion of each Infusion Cycle, participants will be evaluated monthly for 3 months to determine if they meet criteria for 1) redosing with additional 4-weeks of IV BCV, 2) initiation/continuation of Clinical Monitoring or 3) definition of Treatment Failure (leading to optional withdrawal from study and pursuit of rescue treatments). As long as less than 12 weeks of cumulative dosing have been pursued, redosing may be offered.
Upon completion of treatment, participants will be monitored for up to 12 months.
Objectives:
Primary Objective:
-To describe the safety and tolerability of IV BCV 20mg (or 0.4mg/kg if participant weighs\<50kg) dosed twice weekly for a cumulative total of up to 12 weeks.
Secondary Objectives:
Exploratory Objectives:
-To investigate pharmacodynamics and effect of IV BCV in urine, blood and CSF.
Endpoints:
Primary Endpoint:
-Number of treatment-related adverse events (AEs) of Grade 3 severity or higher as determined by Common Terminology Criteria for Adverse Events (CTCAE 6.0)
Secondary Endpoints:
Exploratory Endpoints:
-Exploratory measures in urine, blood and CSF to investigate pharmacodynamics of IV BCV, including virological and immunological changes in response to study intervention.
29 studies on the registry are indexed under Leukoencephalopathy, Progressive Multifocal; 7 are open to participants now.
This study's planned enrollment of 24 is close to the median of 24 across 15 interventional studies indexed under Leukoencephalopathy, Progressive Multifocal.
Browse Leukoencephalopathy, Progressive Multifocal studies →National Institute of Neurological Disorders and Stroke (NINDS) is the lead sponsor of 601 studies on the registry; 56 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 8 (44%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
EXCLUSION CRITERIA:
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.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
experimental treatment arm
Drug: Brincidofovir
intravenous administraion of anti-viral agent
Incidence of treatment-related adverse events (AEs) of Grade 3 severity or higher as determined by Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: Over duration of trial participation
Incidence of treatment-related AEs, regardless of severity
Time frame: over duration of trial
Change from baseline in JCPyV load in CSF upon completion of each Treatment Block
Time frame: at end of each treatment block
Proportion of patients with 0.25log decline or greater in JCPyV load in CSF upon completion of each Treatment Block
Time frame: at end of each treatment block
Time to increase in JCPyV load in CSF during monitoring phase upon treatment completion
Time frame: over duration of trial participation
Number of Treatment Blocks and duration of treatment phase
Time frame: dependent on duration of participation: 1 month - 3 months
Number of patients meeting Treatment Failure Criteria
Time frame: At end of each treatment block
Change from baseline in performance and standardized disability rating scales at 6, 9 and 12 months
Time frame: 6, 9 and 12 months
Change from baseline in PML lesion burden by brain MRI at 3, 6 9 and 12 months
Time frame: 3, 6, 9 and 12 months
Survival at 3, 6, 9 and 12 months
Time frame: 3, 6, 9 and 12 months
Plan to share: No
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Studies of the drug tested here: Brincidofovir
Leukoencephalopathy, Progressive Multifocal →
National Institute of Neurological Disorders and Stroke (NINDS) →