Progressive Multifocal LeukoencephalopathyEarly Phase 1NCT04781309
NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy
A Early Phase 1 study testing NT-I7 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 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy
- What is being tested?
- NT-I7
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 2021to 7 Nov 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
...
Read the 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.
- Being tested
- NT-I7
- Keywords
- Absolute Lymphocyte Count, safety and tolerability of NT-I7
- 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.
NT-I7Drug
NT-I7 is a recombinant human interleukin-7 fused to a hybrid fragment crystallizable region of a human antibody (hyFc). NT-I6 has a molecular weight of 104 kD. The active moiety of NT-I7 is recombinant human interleukin-7 (rhIL-7), containing human IL-7 (amino acids 4 through 155) and exhibiting all known functions of endogenous human IL-7.
| Study group | Role | What they receive |
|---|---|---|
| NT-I7 | Experimental | 480 microgram/kg IM (initial dose) Receives: Drug: NT-I7 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: over 6months following study drug administration
Secondary outcomes (3)
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.
Measured: at each study timepoint
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.
Measured: at each study timepoint
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.
Measured: at each study timepoint
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2021
- Study start5 May 2021
- Primary completion7 Nov 2025
- Study completion7 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Collaborators
- NeoImmuneTech
- 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
- NCT04781309
- Sponsor's protocol ID
- 10000126
- Other IDs
- 000126-N
- Status last verified
- 14 Nov 2025
- First submitted
- 3 Mar 2021
- Last updated
- 18 Nov 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04781309
- Acronym / sponsor ID
- 10000126
- Keywords
- Absolute Lymphocyte Count, safety and tolerability of NT-I7
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Collaborators
- NeoImmuneTech
- Study start
- 5 May 2021 (actual)
- Primary completion
- 7 Nov 2025 (actual)
- Study completion
- 7 Nov 2025 (actual)
- First posted
- 4 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NT-I7 | Experimental | Drug: NT-I7480 microgram/kg IM (initial dose) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NT-I7NT-I7 is a recombinant human interleukin-7 fused to a hybrid fragment crystallizable region of a human antibody (hyFc). NT-I6 has a molecular weight of 104 kD. The active moiety of NT-I7 is recombinant human interleukin-7 (rhIL-7), containing human IL-7 (amino acids 4 through 155) and exhibiting all known functions of endogenous human IL-7. | Drug | NT-I7 |
Primary outcome
the longitudinal change in absolute lymphocyte count over 6 months following study drug administration
Time frame: over 6months 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
3 secondary outcomes
Safety
Time frame: at each study timepoint
Change in lymphocyte subsets, including CD4, CD8, and CD19 positive cells
Time frame: at each study timepoint
Disease course
Time frame: at each study timepoint
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Irene CM Cortese, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing NT-I7 in people with Progressive Multifocal Leukoencephalopathy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the longitudinal change in absolute lymphocyte count over 6 months following study drug administration (time frame: over 6months following study drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.