Intravenous brincidofovir treatment for progressive multifocal leukoencephalopathy
Safety and Tolerability of Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study
This trial will test whether intravenous brincidofovir given twice weekly for up to 12 weeks can help adults with progressive multifocal leukoencephalopathy (PML).
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 18 Years to 99 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT07511049 on ClinicalTrials.gov |
What this trial studies
This is a Phase 2 pilot study testing safety and tolerability of IV brincidofovir (BCV) in adults with confirmed PML and positive JCPyV DNA in cerebrospinal fluid. Eighteen participants will receive BCV 20 mg (or 0.4 mg/kg if <50 kg) twice weekly in 4-week infusion cycles for up to three cycles (12 weeks total), with the first three participants enrolled in a staggered fashion. Baseline evaluations include physical exam, blood tests, contrast brain MRI, and lumbar puncture, and participants are monitored monthly between cycles and for up to 12 months after treatment. Secondary data collection will track changes in JCPyV viral load in CSF and clinical course.
Who should consider this trial
Good fit: Adults aged 18 or older with clinically definite or probable PML and a positive JCPyV PCR in CSF who are medically stable and can travel to the NIH Clinical Center are eligible.
Not a fit: People with significant liver enzyme or bilirubin elevation, severe kidney dysfunction (eGFR <30 mL/min), hypersensitivity to brincidofovir/cidofovir, or who cannot travel to the study site are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, this treatment could offer a targeted antiviral option that lowers JC virus burden and potentially improves outcomes for people with PML.
How similar studies have performed: Brincidofovir is approved for other viral indications (smallpox) but its use for PML is novel and clinical evidence in PML is currently very limited.
Eligibility criteria
Show full inclusion / exclusion criteria
* INCLUSION CRITERIA: * 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 CRITERIA: * 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
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Irene CM Cortese, M.D. — National Institute of Neurological Disorders and Stroke (NINDS)
- Study coordinator: Irene CM Cortese, M.D.
- Email: corteseir@ninds.nih.gov
- Phone: (301) 496-1801
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.