NT-I7 for Progressive Multifocal Leukoencephalopathy

Overseen By Anita M Fletcher, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Must not be taking: Immune-suppressive medications

Disqualifiers: Autoimmune CNS, Immune-mediated vital organ, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 23

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, NT-I7 (also known as Efineptakin alfa), to determine its effectiveness for people with progressive multifocal leukoencephalopathy (PML), a serious brain infection. PML affects individuals with weakened immune systems and can cause issues with thinking, vision, movement, and speech. Researchers aim for NT-I7 to boost certain immune cells, called lymphocytes, to help control the infection. Individuals with PML and a specific type of low immune cell count might be suitable for this trial. Participants will receive up to three doses of the drug and must visit the study site for tests and monitoring over 12 to 19 months. As an Early Phase 1 trial, this research focuses on understanding how NT-I7 works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop ongoing treatment with immune-suppressive medications, except for short-term use of topical steroids or systemic steroids for less than two weeks.

Is there any evidence suggesting that NT-I7 is likely to be safe for humans?

Research has shown that NT-I7, a long-lasting form of IL-7, has been safe in several studies. For instance, one study found that GX-I7, similar to NT-I7, safely increased T cells (a type of immune cell) without causing serious side effects. Another study with animals like monkeys demonstrated that a treatment similar to NT-I7 was safe and did not cause any immediate negative reactions. These results suggest that NT-I7 is generally well-tolerated. However, since this is an early-stage trial, there might be limited safety data specifically for NT-I7 in humans with PML. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Progressive Multifocal Leukoencephalopathy, which often focus on managing symptoms and controlling the underlying immune response, NT-I7 offers a novel approach. NT-I7 is unique because it is an experimental immunotherapy that works by boosting the body's immune system. By providing an initial dose of 480 microgram/kg intramuscularly, NT-I7 aims to enhance the production of T cells, which are crucial for fighting the JC virus responsible for this condition. Researchers are excited about NT-I7 because it targets the immune system directly, potentially offering a more effective way to combat this challenging disease.

What evidence suggests that NT-I7 might be an effective treatment for PML?

Research has shown that NT-I7, a long-lasting form of the protein interleukin-7, might aid individuals with Progressive Multifocal Leukoencephalopathy (PML) by strengthening their immune system. In one case, a 66-year-old man with PML improved after receiving three doses of NT-I7. This drug increases the number of lymphocytes, crucial immune cells that fight infections. Earlier studies have successfully used similar treatments to boost immune cell numbers in patients with other illnesses. Although this evidence is still early, it suggests that NT-I7 could be a promising way to manage PML by enhancing the body's immune response. Participants in this trial will receive NT-I7 to further evaluate its effectiveness in treating PML. ^{1 2 3 4 6}

Who Is on the Research Team?

Irene CM Cortese, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

Adults over 18 with Progressive Multifocal Leukoencephalopathy (PML) and low lymphocyte counts, enrolled in Protocol #13-N-0017. Participants must be able to travel for study visits, provide consent, follow procedures, and use reliable birth control if applicable. Excludes those on immune-suppressive meds (except short-term steroids), with autoimmune CNS diseases or conditions that could affect the trial.

Inclusion Criteria

My CD4 or CD8 cell count is 200 or less and can't be quickly fixed.

You have been diagnosed with a specific brain infection called PML using specific criteria from 2013.

I can travel to NIH for study visits.

Exclusion Criteria

Unwilling to have coded samples and/or data saved or used in other studies

You are currently receiving experimental treatments for PML that could affect the study results.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive up to 3 doses of NT-I7 by injection into the muscle, with inpatient observation for the first 7 days following any experimental drug dosing.

7 days

7-day inpatient stay

Second Inpatient Stay

Participants return for a second 7-day inpatient stay by Day 21.

7 days

7-day inpatient stay

Outpatient Visits

Scheduled outpatient visits at NIH at month 2, 3, 6, 9, and 12 following any drug dosing.

12 months

5 outpatient visits

Follow-up

Follow-up phone calls will be conducted at month 4, 5, 7, and 8 to monitor safety and effectiveness.

4 months

4 follow-up phone calls

What Are the Treatments Tested in This Trial?

Interventions

• NT-I7

Trial Overview The trial is testing NT-I7, a new drug designed to boost lymphocyte numbers which may help fight PML infection. It involves an initial 7-day hospital stay followed by outpatient visits and phone calls for up to 19 months. Procedures include injections of NT-I7 into the muscle, lumbar punctures, blood draws, urine samples, and MRI scans with contrast agents.

How Is the Trial Designed?

Group I: NT-I7 Experimental Treatment 1 Intervention

480 microgram/kg IM (initial dose)

NT-I7 is already approved in United States for the following indications:

Approved in United States as NT-I7 for:

• Orphan drug designation for glioblastoma multiforme
• Orphan drug designation for advanced pancreatic cancer

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

NeoImmuneTech

Industry Sponsor

Trials

16

Recruited

780+

Published Research Related to This Trial

A 66-year-old man with progressive multifocal leukoencephalopathy (PML) and severe lymphocytopenia showed improvement after receiving three doses of interleukin-7 (IL-7), with no adverse effects reported.

IL-7 treatment led to a significant increase in lymphocyte counts, stabilizing MRI lesions and resulting in mild neurological improvement, suggesting its potential as a therapeutic option for PML in patients with idiopathic CD8+ lymphocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-7 treatment of PML in a patient with idiopathic lymphocytopenia. Miskin, DP., Chalkias, SG., Dang, X., et al.[2018]

A 61-year-old man with progressive multifocal leukoencephalopathy and idiopathic CD4+ T-cell lymphocytopenia showed significant clinical improvement after receiving recombinant human interleukin 7, including regression of brain abnormalities and clearance of JC virus DNA from plasma.

Despite initial success, the patient's CD4+ T-cell count returned to baseline after one year, highlighting the need for further research to understand the long-term effects and potential of interleukin 7 in treating similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of progressive multifocal leukoencephalopathy with interleukin 7. Alstadhaug, KB., Croughs, T., Henriksen, S., et al.[2015]

The hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) significantly enhances the antitumor response by expanding CD8+ T cells in the tumor microenvironment, leading to increased tumor-reactive T cells with improved effector functions.

When combined with chemotherapy and checkpoint inhibitors, rhIL-7-hyFc not only boosts the antitumor response but also restores CD8+ T cell levels even in conditions of low T lymphocyte counts, suggesting its potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. Kim, JH., Kim, YM., Choi, D., et al.[2022]

A patient with severe lymphopenia following bone marrow transplantation developed progressive multifocal leukoencephalopathy, a serious brain infection caused by the John Cunningham virus (JCV).

Treatment with recombinant human interleukin-7 successfully restored T-cell responses against JCV, cleared the virus from the cerebrospinal fluid, and led to significant clinical improvement, highlighting its potential as an effective therapy in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of recombinant human interleukin 7 in a patient with severe lymphopenia-related progressive multifocal leukoencephalopathy. Gasnault, J., de Goër de Herve, MG., Michot, JM., et al.[2020]

The study demonstrated that MVA-hIL-7-Fc, a recombinant virotherapy, is safe for use in nonhuman primates, with no acute adverse reactions observed after a single intravenous injection.

The treatment effectively stimulated the immune system, leading to an expansion of various immune cells, including CD4 and CD8 T cells, indicating its potential for enhancing immune responses in sepsis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous injection of a novel viral immunotherapy encoding human interleukin-7 in nonhuman primates is safe and increases absolute lymphocyte count. Coupet, CA., Dubois, C., Evlachev, A., et al.[2023]

In a study of 64 patients with progressive multifocal leukoencephalopathy (PML) treated with recombinant human IL-7 (rhIL-7), the one-year survival rate was 54.7%, with survival linked to increases in blood lymphocytes and CD4+ T cells, as well as decreases in JCV DNA in cerebrospinal fluid.

The treatment was generally well-tolerated, with side effects mostly being mild, such as local reactions and flu-like symptoms, indicating that rhIL-7 may be a safe option for restoring immunity against the JC virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Progressive Multifocal Leukoencephalopathy Treated by Interleukin-7. Lajaunie, R., Mainardi, I., Gasnault, J., et al.[2022]

A novel hybrid protein, TNFR-hyFc, was developed to reduce unwanted immune responses like antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are concerns with existing TNF-α blockers like etanercept.

Pre-clinical evaluations showed that TNFR-hyFc has a similar biochemical profile to etanercept but is slightly larger and more acidic, suggesting it may offer a safer alternative with reduced side effects in treating conditions related to TNF-α.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical characterization of a new recombinant TNF receptor-hyFc fusion protein expressed in CHO cells. Lee, JH., Yeo, J., Park, HS., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04781309

NCT04781309 | NT-I7, a Long-Acting Recombinant IL-7 ... Study Description: This protocol will test whether NT-I7 is a viable strategy for promoting immune reconstitution in lymphopenic patients with PML. Twelve ...

2. withpower.com withpower.com/trial/early-phase-1-leukoencephalopathies-4-2021-376cb?condition=&query=NT-I7&overallStatus=Recruiting&hasNoPlacebo=false

NT-I7 for Progressive Multifocal Leukoencephalopathy A 66-year-old man with progressive multifocal leukoencephalopathy (PML) and severe lymphocytopenia showed improvement after receiving three doses of interleukin ...

3. delta.larvol.com delta.larvol.com/Products/?ProductId=93e2cc69-371d-4a60-bd3e-55ae7018a431

Hyleukin-7 (efineptakin alfa) / Genexine, NeoImmuneTech, ... NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy ...

4. nature.com nature.com/articles/s41416-025-03069-3

GX-I7, a long-acting IL-7, safely and effectively increased ... This study, conducted in patients with advanced solid tumours at three hospitals in Korea, involved intramuscular GX-I7 administration across ...

5. medrxiv.org medrxiv.org/content/10.1101/2024.02.12.23299638v1.full.pdf

GX-I7(rhIL-7-hyFc, efineptakin alfa), a long-acting IL-7, ... GX-I7 treatment was observed. 87. Conclusion: These findings support the use of GX-I7 as a safe and effective T cell-amplifying agent.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39915263/

Phase I study of efineptakin alfa (NT-I7) for the ... - PubMed - NIH Preliminary data demonstrate safety and activity of IL-7 in patients with KS and activity specifically among individuals HIV-associated KS.