Clinical trial NCT04781309: NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Progressive Multifocal Leukoencephalopathy
Keywords: Absolute Lymphocyte Count
safety and tolerability of NT-I7
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: NeoImmuneTech
First posted: 2021-03-04
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

...

Detailed description: Study Description:

This protocol will test whether NT-I7 is a viable strategy for promoting immune reconstitution in lymphopenic patients with PML. Twelve evaluable adults with PML and lymphopenia (CD4 or CD8 T cell count of \<=200 cells/dL), without a history of autoimmune disease affecting vital organs, 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.

Eligibility criteria: * INCLUSION CRITERIA:
* Adults (18 years of age or older)
* Definite or Probable PML (2013 AAN Consensus Diagnostic Criteria)
* CD4 and/or CD8 lymphopenia \<= 200 cells/dL 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 immune-mediated disease affecting vital organ
* 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

Primary outcomes:
measure: the longitudinal change in absolute lymphocyte count over 6 months following study drug administration
timeFrame: over 6months following study drug administration
Secondary outcomes:
measure: Safety
timeFrame: at each study timepoint
measure: Change in lymphocyte subsets, including CD4, CD8, and CD19 positive cells
timeFrame: at each study timepoint
measure: Disease course
timeFrame: at each study timepoint
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
name: Irene CM Cortese, M.D.
role: PRINCIPAL_INVESTIGATOR
References: