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

NCT07511049 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10002635002635-N
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Progressive Multifocal Leukoencephalopathy

Keywords

Safety and Tolerability of Intravenous Brincidofovir; safety, tolerability, brincidofovir, PML, JCV

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related adverse events (AEs) of Grade 3 severity or higher as determined by Common Terminology Criteria for Adverse Events (CTCAE)

  Over duration of trial participation

Secondary Outcomes (9)

• Incidence of treatment-related AEs, regardless of severity

  over duration of trial

• Change from baseline in JCPyV load in CSF upon completion of each Treatment Block

  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

  at end of each treatment block

• Time to increase in JCPyV load in CSF during monitoring phase upon treatment completion

  over duration of trial participation

• Number of Treatment Blocks and duration of treatment phase

  dependent on duration of participation: 1 month - 3 months

Study Arms (1)

Brincidofovir treatment arm

EXPERIMENTAL

experimental treatment arm

Drug: Brincidofovir

Interventions

Brincidofovir DRUG

intravenous administraion of anti-viral agent

Brincidofovir treatment arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Gosert R, Rinaldo CH, Wernli M, Major EO, Hirsch HH. CMX001 (1-O-hexadecyloxypropyl-cidofovir) inhibits polyomavirus JC replication in human brain progenitor-derived astrocytes. Antimicrob Agents Chemother. 2011 May;55(5):2129-36. doi: 10.1128/AAC.00046-11. Epub 2011 Mar 14.

  PMID: 21402853 BACKGROUND

• Jiang ZG, Cohen J, Marshall LJ, Major EO. Hexadecyloxypropyl-cidofovir (CMX001) suppresses JC virus replication in human fetal brain SVG cell cultures. Antimicrob Agents Chemother. 2010 Nov;54(11):4723-32. doi: 10.1128/AAC.00837-10. Epub 2010 Sep 7.

  PMID: 20823288 BACKGROUND

• Grimley MS, Chemaly RF, Englund JA, Kurtzberg J, Chittick G, Brundage TM, Bae A, Morrison ME, Prasad VK. Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial. Biol Blood Marrow Transplant. 2017 Mar;23(3):512-521. doi: 10.1016/j.bbmt.2016.12.621. Epub 2017 Jan 5.

  PMID: 28063938 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukoencephalopathy, Progressive Multifocal

Interventions

brincidofovir

Condition Hierarchy (Ancestors)

Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Virus Diseases; Polyomavirus Infections; DNA Virus Infections; Slow Virus Diseases; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Neuroinflammatory Diseases

Study Officials

• Irene CM Cortese, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irene CM Cortese, M.D.

CONTACT

(301) 496-1801; corteseir@ninds.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2026
• First Posted: April 6, 2026
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-03-26

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)