Progressive Multifocal Leukoencephalopathy Clinical Trial
Official title:
A Pilot Study of NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy
Background: Progressive multifocal leukoencephalopathy (PML) is a brain infection. It is caused by a virus. PML can happen in people with a weakened immune system. PML is associated with cognitive and visual impairment as well as motor and speech disturbances. There is no treatment for PML. Researchers want to see if a new drug can help. Objective: To see if the drug NT-I7 can help increase lymphocyte numbers, which may help control PML infection. Eligibility: Adults ages 18 and older with PML who are enrolled in Protocol #13-N-0017. Design: Participants will be screened under Protocol #13-N-0017. Participants will have a 7-day inpatient stay, outpatient visits, and follow-up phone calls. Participants will have a medical history and physical exam. They will give urine samples. Blood will be drawn from an arm vein or through an intravenous (IV) catheter. Participants will get up to 3 doses of NT-I7. It will be given by injection into the muscle. Participants will have lumbar punctures ( spinal taps ). A thin needle will be inserted into the spinal canal in the lower back. Cerebrospinal fluid will be removed. X-ray may be used to guide the procedure. Participants will have magnetic resonance imaging (MRI) of the brain. The MRI scanner is a metal cylinder surrounded by a magnetic field. During MRIs, participants will lie on a table that slides in and out of the scanner. Soft padding or a coil will be placed around their head. They will get gadolinium, a contrast agent, through an IV catheter. Participation will last for 12 to 19 months.
Status | Recruiting |
Enrollment | 12 |
Est. completion date | January 31, 2026 |
Est. primary completion date | January 31, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 120 Years |
Eligibility | - INCLUSION CRITERIA: - Adults (18 years of age or older) - Definite or Probable PML (2013 AAN Consensus Diagnostic Criteria) - CD4 and/or CD8 lymphopenia less than or equal to 200 cells/dL from any cause that is not readily reversible within one month - Enrolled in 13-N-0017 - Ability to provide own consent at study entry - Ability to travel to NIH for study visits - Willingness to comply with all study procedures - If able to become pregnant or to father a child, patient must agree to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy) for the duration of the study EXCLUSION CRITERIA: - Age < 18 years of age - Ongoing treatment with immune-suppressive medications (exception: topical steroid use and all forms of systemic steroids with durations less than 2 weeks) - Concurrent treatment with experimental therapies for PML that would interfere with or confound assessment of study outcomes - History of underlying autoimmune disease involving the CNS - Contraindication to any study procedures that would compromise ability to safely monitor the patient - History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with study participation; or not in the best interest of the subject to participate, in the opinion of the treating investigator - Women who are pregnant or breastfeeding - Unwilling to have coded samples and/or data saved or used in other studies |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Neurological Disorders and Stroke (NINDS) | NeoImmuneTech |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | the longitudinal change in absolute lymphocyte count over 6 months following study drug administration | determine the kinetics and magnitude of effect of NT-I7 on absolute lymphocyte counts (ALC) in patients with PML and underlying lymphopenia from various causes, in order to inform appropriate design of a future study | over 6months following study drug administration | |
Secondary | Safety | assessed by the occurrence of treatment-related adverse events. These adverse events will be tabulated separately by timepoint to identify any trends in the data and will be described using number and percent. | at each study timepoint | |
Secondary | Change in lymphocyte subsets, including CD4, CD8, and CD19 positive cells | These values will be investigated first descriptively at each timepoint using mean and SD or median and IQR, and then graphically. Key comparisons of interest will include baseline to Month 3 and baseline to Month 6. | at each study timepoint | |
Secondary | Disease course | These endpoints include quantification of JCV DNA in CSF and blood, change in Modified Rankin Scale score, change in Karnofsky Performance Scale score, change in PML lesion extension, change in pattern of contrast enhancement by brain MRI and survival. Key comparisons of interest will include baseline to Month 3 and baseline to Month 6. Here, the goal is to provide some initial proof of principle that the disease course is being impacted in a measurable way, particularly beyond Month 3. | at each study timepoint |
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