Bethesda, Maryland 20892

  • Progressive Multifocal Leukoencephalopathy

Purpose:

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.


Study summary:

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 (PML). Study Description: This protocol will test whether NT-I7 is a viable strategy for promoting immune reconstitution in lymphopenic patients with PML. Twelve adults with PML and lymphopenia (CD4 or CD8 T cell count of less than or equal to 200 cells/dL) from all causes will complete this pilot study. Patients will be observed as inpatient for the first 7 days following any experimental drug dosing. To follow, patients will return to NIH for a second 7-day inpatient stay by Day 21, and then for scheduled outpatient visits at NIH at month 2, 3, 6, 9 and 12 following any drug dosing. Follow up phone calls will be conducted at month 4, 5, 7 and 8. Patients may be eligible for a second dose of NT-I7 at higher dose if target ALC (1000/microliter) not reached, or at same dose if initial response is adequate but not sustained, for a maximum of 3 doses. The primary outcome measure is change in absolute lymphocyte counts (ALC). Secondary outcomes include safety and tolerability. Exploratory clinical, radiological, and laboratory measures will be obtained to investigate mechanism of action of NT-I7 and for biomarker development. Objectives: Primary Objective: To determine the kinetics and magnitude of effect of NT-I7 on absolute lymphocyte counts in patients with PML and underlying lymphopenia from various causes, in order to inform appropriate design of a future study. Secondary Objectives: (1) To assess safety and tolerability of NT-I7. (2) To determine kinetics and magnitude of effect of NT-I7 on lymphocyte subsets. (3) To investigate effect of NT-I7 on PML disease course. (4) To investigate mechanism of action of NT-I7. Endpoints: Primary Endpoint: Change in absolute lymphocyte counts (ALC) over 6 months. Secondary Endpoints: (1) Adverse event tables. (2) Change in lymphocyte subset counts, including CD4, CD8 and CD19 positive cells (3) Change in standardized disability rating scales, PML lesion extension by brain MRI, viral quantification in CSF and survival. (4) Exploratory serological and CSF measures to investigate immune response to JCV and mechanism of action of NT-I7. Study Population: Adults with definite PML with detectable JCV in CSF and CD4 and/or CD8 lymphopenia will be recruited. Phase: Pilot study Description of Sites/Facilities Enrolling Participants: NIH Clinical Center Description of Study Intervention: A single dose of NT-I7 480micrograms/kg IM will be administered to all patients. Patients will be eligible for re-dosing of NT-I7 at 720microgram/kg IM if minimum target ALC is not achieved by Day 27. Patients will be eligible for re-dosing at same dose (480 microgram/kg or 720microgram/kg) if minimum target ALC is reached but not sustained at least until Month 3. Study Duration: 36 months for data collection and analysis of primary and secondary outcomes Participant Duration: Up to 19 months


Criteria:

- 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) - 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 participation for the full duration of the trial; 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 INCLUSION OF VULNERABLE PARTICIPANTS: Selection will be equitable among eligible patients. Inclusion of decisionally impaired adults: Consent capacity is required at the time of enrollment to ensure that participants are able to fully express understanding of participation prior to starting this more than minimal risk protocol. The study question should be able to be answered by enrolling those that have consent capacity at the time of enrollment, thus maximizing the risk benefit ratio. At the time of enrollment, while participants have consent capacity, they will be asked to appoint a DPA for research and health care to be invoked if they subsequently lose consent capacity. Patients with PML may lose consent capacity with disease progression, and such participants will be allowed to remain in the study. This is justified, given the study question cannot be answered without enrolling people with PML and there is the possibility of direct benefit. In addition, at the time of enrollment the participants had capacity, agreed to full participation, and chose a surrogate to speak on their behalf should they lose capacity. This participant appointed DPA will be invoked should it be determined the subject no longer has consent capacity. Inclusion of employees: NIH employees and staff will not be solicited for participation but will not be excluded if they express the desire to enroll. NIH staff and family members of study team members may be enrolled in this study as this population meets the study entry criteria. Employees and staff who participate in this protocol during work hours will be informed that they must obtain their supervisor s permission. Neither participation nor refusal to participate as a subject in the research will have an effect, either beneficial or adverse, on the participant s employment, training or position at NIH.


NCT ID:

NCT04781309


Primary Contact:

Principal Investigator
Irene CM Cortese, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)

Frances C Andrada, C.R.N.P.
Phone: (301) 496-3825
Email: andradaf@mail.nih.gov


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone: 800-411-1222
Email: prpl@cc.nih.gov

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: June 12, 2021

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