RecruitingPhase 2NCT07511049

Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study

Safety and Tolerability of Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Enrollment

24 participants

Start Date

May 6, 2026

Study Type

INTERVENTIONAL

Conditions

Progressive Multifocal Leukoencephalopathy

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 99 Years

Inclusion Criteria7

Able to provide informed consent
Stated willingness to comply with study procedures and to participate for the duration of the study including follow-up
Actively progressing, clinically definite or probable PML (2013 AAN Consensus Diagnostic Criteria)
Positive PCR for JCPyV in CSF
Age 18 or older
Medically stable and able to tolerate travel to NIH
Participants of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study

Exclusion Criteria7

ALT or AST > 5 x the ULN, total bilirubin > 3 mg/dL (SI: >51 micromol/L), or spontaneous prothrombin time-international normalized ratio (PT-INR) > 2 x ULN within 7 days prior to Day 1
An estimated glomerular filtration rate of < 30 mL/min within 7 days prior to Day 1
Hypersensitivity to CDV or to BCV or its formulation excipients, or prior intolerance to these agents that, in the opinion of the investigator, would pose an unacceptable safety risk.
Active CNS disease other than PML that, in the opinion of the investigator, would confound study assessments or pose an unacceptable safety risk.
Contraindication to MRI (including cardiac pacemakers and some infusion pumps, other metallic implants, metallic foreign objects)
Medical contraindication to LP
Positive pregnancy test or nursing