Progressive Multifocal LeukoencephalopathyPhase 2NCT07511049
Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study
A Phase 2 study testing Brincidofovir in people with Progressive Multifocal Leukoencephalopathy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy
- What is being tested?
- Brincidofovir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jun 2026to 31 Dec 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to provide informed consent or have a designated legally authorized representative (LAR) to provide 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Neuroimmunology Clinic, 301-496-3825, corteseir@ninds.nih.gov
NIH Clinical Center Office of Patient Recruitment (OPR), (800) 411-1222, ccopr@nih.gov
About this study
Official title: Safety and Tolerability of Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study
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.
Read more
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.
Read the detailed description
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:
- To investigate kinetics and magnitude of antiviral effect of IV BCV on JCPyV load in CSF in participants with PML.
- To investigate effect of IV BCV on clinical and radiological PML disease course.
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:
- Number of treatment-related AEs, irrespective of grade
- Change from baseline in JCPyV load in CSF at completion of Infusion Cycles 1, 2 and 3
- Proportion of participants with 0.25 log decline or greater in JCPyV load in CSF at completion of Infusion Cycles 1, 2 and 3
- Number of Infusion Cycles
- Time to increase in JCPyV load in CSF during monitoring phase
- Number of participants meeting criteria for Treatment Failure
- Change in performance measures and standardized disability rating scales from baseline to Month 6, 9 and 12 (or last assessment)
- Change in PML lesion burden by MRI from baseline to Month 3, 6, 9 and 12 (or last assessment)
- Survival at 3, 6, 9 and 12 months
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.
- Being tested
- Brincidofovir
- Keywords
- Safety and Tolerability of Intravenous Brincidofovir, safety, tolerability, brincidofovir, PML, JCV
- Medical subject headings
- Leukoencephalopathy, Progressive Multifocal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrincidofovirDrug
intravenous administraion of anti-viral agent
| Study group | Role | What they receive |
|---|---|---|
| Brincidofovir treatment arm | Experimental | experimental treatment arm Receives: Drug: Brincidofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-related adverse events (AEs) of Grade 3 severity or higher as determined by Common Terminology Criteria for Adverse Events (CTCAE)
Measured: Over duration of trial participation
Secondary outcomes (9)
Incidence of treatment-related AEs, regardless of severity
Measured: over duration of trial
Change from baseline in JCPyV load in CSF upon completion of each Treatment Block
Measured: 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
Measured: at end of each treatment block
Time to increase in JCPyV load in CSF during monitoring phase upon treatment completion
Measured: over duration of trial participation
Number of Treatment Blocks and duration of treatment phase
Measured: dependent on duration of participation: 1 month - 3 months
Number of patients meeting Treatment Failure Criteria
Measured: At end of each treatment block
Change from baseline in performance and standardized disability rating scales at 6, 9 and 12 months
Measured: 6, 9 and 12 months
Change from baseline in PML lesion burden by brain MRI at 3, 6 9 and 12 months
Measured: 3, 6, 9 and 12 months
Survival at 3, 6, 9 and 12 months
Measured: 3, 6, 9 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2026
- Study start5 Jun 2026
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Progressive Multifocal LeukoencephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irene CM Cortese, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07511049
- Sponsor's protocol ID
- 10002635
- Other IDs
- 002635-N
- Status last verified
- 20 Jul 2026
- First submitted
- 3 Apr 2026
- Last updated
- 22 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21402853Jiang 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.
PubMed 20823288Grimley 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.
PubMed 28063938