NT-I7 for Idiopathic CD4 Lymphopenia

Overseen By Andrea Lisco, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Systemic glucocorticosteroids, Immunomodulants

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 36 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, NT-I7, to determine its effectiveness for individuals with idiopathic CD4 lymphopenia (ICL), a condition characterized by insufficient CD4 T cells, increasing susceptibility to severe infections and diseases. The trial aims to assess whether NT-I7 can safely boost CD4 T cell counts, potentially offering a new treatment option. Individuals with ICL participating in a related NIH study might be suitable candidates for this trial. Participants will receive NT-I7 injections and undergo regular check-ups to monitor their response. As a Phase 1 trial, this research seeks to understand how NT-I7 functions in people, providing participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using systemic glucocorticosteroids or immunomodulants (medications that affect the immune system) within 3 months of screening, except for certain types like nasal sprays or topical steroids.

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

Research has shown that GX-I7, also known as NT-I7, boosts T cells, which are crucial for the immune system. Earlier trials found this treatment to be safe and well-tolerated. Studies have demonstrated that GX-I7 effectively increases T-cell counts without causing serious side effects.

Although no treatment is entirely risk-free, evidence suggests that GX-I7 is a promising option with a strong safety record. However, discussing this with a doctor is essential to understand its relevance to individual circumstances. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Idiopathic CD4 Lymphopenia (ICL), which often focus on managing symptoms and preventing infections, NT-I7 uses recombinant human interleukin (IL) 7-hyFc to actively boost the immune system. This treatment is unique because IL-7 is a key cytokine that promotes the survival and proliferation of T-cells, potentially addressing the root cause of ICL by increasing CD4 T-cell counts. Researchers are excited about NT-I7 because it represents a novel approach that could improve immune function more effectively and sustainably than current options.

What evidence suggests that NT-I7 might be an effective treatment for idiopathic CD4 lymphopenia?

Studies have shown that the drug NT-I7, also known as efineptakin alfa, can effectively increase the number of important immune cells called CD4 T cells. Previous research found that NT-I7 safely boosts CD4 and CD8 T cells in people with certain conditions, like cancer. This is promising because individuals with idiopathic CD4 lymphopenia (ICL) have low levels of these cells, making them more vulnerable to infections and other diseases. NT-I7 works by signaling the body to produce more of these crucial immune cells. Early findings suggest that NT-I7 could improve immune function for those with ICL by increasing CD4 T cell counts. Participants in this trial will receive NT-I7 to evaluate its effectiveness in increasing CD4 T cell counts in individuals with ICL. ^{1 4 5 6 7}

Who Is on the Research Team?

Andrea Lisco, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Adults aged 18-75 with Idiopathic CD4 Lymphopenia (ICL), a condition where they have dangerously low levels of certain immune cells, can join this trial. They must be part of another NIH study and not pregnant or breastfeeding. People with HIV, hepatitis B/C, other immunodeficiencies, recent cancer treatments, severe illnesses, or using certain medications are excluded.

Inclusion Criteria

Co-enrolled in NIH protocol 09-I-0102, Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia (EPIC) study (NCT0086726)

Able to provide informed consent

Participants who can become pregnant or who can impregnate their partner must agree to use 2 highly effective methods of contraception, at least 1 of which must be a barrier method, when engaging in sexual activities that can result in pregnancy, beginning 28 days prior to baseline until the final study visit. Acceptable methods of contraception include male or female condom, diaphragm or cervical cap with a spermicide, hormonal contraception, intrauterine device

Exclusion Criteria

I haven't taken systemic steroids or immune system drugs in the last 3 months, except for nasal sprays or inhalers and creams.

Receipt of any other investigational agents within 3 months of screening

Any condition that, in the opinion of the study team contraindicates participation in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 3 doses of NT-I7, each about 12 weeks apart, with blood drawn at each dose visit and additional tests conducted

36 weeks

Multiple visits (in-person) including 5 days before each dose and 2 and 4 weeks after each dose

Follow-up

Participants are monitored for safety and effectiveness after treatment, with 3 follow-up visits every 3 months

24 weeks

3 visits (in-person)

End-of-study evaluation

Final study visit to evaluate the number and severity of adverse events and immunologic effects

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Recombinant human interleukin (IL) 7-hyFc

Trial Overview The trial is testing NT-I7 (Efineptakin Alfa), a new drug designed to increase CD4 T cell counts in people with ICL. Participants will receive three doses via injection over several months and undergo regular blood tests, leukapheresis procedures to collect white blood cells, and possibly additional exams like lumbar punctures.

How Is the Trial Designed?

Group I: Single Cohort Experimental Treatment 1 Intervention

Patients with ICL who are enrolled in 09-I-0102.

Recombinant human interleukin (IL) 7-hyFc is already approved in European Union, United States for the following indications:

Approved in European Union as Efineptakin alfa for:

• Orphan drug designation for idiopathic CD4 lymphopenia and other conditions

Approved in United States as Efineptakin alfa for:

• Orphan drug designation for advanced pancreatic cancer and other conditions

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

NeoImmuneTech

Industry Sponsor

Trials

16

Recruited

780+

NeoImmune Tech

Collaborator

Trials

4

Recruited

250+

Published Research Related to This Trial

The study of hIL-7-hyFc, involving 30 healthy volunteers, demonstrated that this treatment significantly increased lymphocyte counts, particularly T-cells, with effects peaking three weeks post-administration and lasting for several weeks.

hIL-7-hyFc was well-tolerated with minimal side effects, primarily injection site reactions that resolved on their own, suggesting it could be a safe and effective option for patients with weakened T-cell immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. Lee, SW., Choi, D., Heo, M., et al.[2021]

Interleukin-7 (IL-7) is crucial for the growth and survival of T-lymphocytes, making it a promising treatment option for immunodeficiencies caused by T-cell loss due to diseases like HIV or treatments like chemotherapy.

While IL-7 can help restore T-cell levels in lymphopenia, it may also contribute to autoimmune diseases, suggesting that blocking IL-7 could be beneficial in conditions like Rheumatoid Arthritis and Multiple Sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-7 and lymphopenia. Ponchel, F., Cuthbert, RJ., Goëb, V.[2016]

A new long-acting form of interleukin-7 (rhIL-7-hyFc) has been shown to significantly enhance the effectiveness of CAR T cell therapy by promoting the growth, persistence, and cytotoxicity of CAR T cells in mouse models.

This enhancement leads to long-term tumor-free survival, suggesting that rhIL-7-hyFc could be a valuable addition to CAR T cell treatments for patients with refractory hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. Kim, MY., Jayasinghe, R., Devenport, JM., et al.[2023]

In two phase II trials involving 107 HIV-infected patients, repeated cycles of recombinant human interleukin 7 (r-hIL-7) were found to be safe and well tolerated, with most participants achieving sustained CD4 T-cell counts above 500 cells/µL.

Despite the development of anti-r-hIL-7 antibodies in a significant number of patients, these antibodies did not negatively affect the CD4 T-cell response, indicating that r-hIL-7 can effectively enhance immune restoration in HIV patients on antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results of 2 Phase II Multicenter Studies. Thiébaut, R., Jarne, A., Routy, JP., et al.[2018]

A single administration of long-acting recombinant human IL-7 (hIL-7-hyFc) significantly increased CD8+ and CD4+ T-cell numbers in healthy adults, with effects lasting up to 56 days, indicating its potential for enhancing T-cell immunity.

The treatment did not expand regulatory T cells (Tregs) and preserved the effector functions of antigen-specific CD8+ T cells, suggesting that hIL-7-hyFc could be a promising therapy for patients with weakened immune systems or as an adjuvant in vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions. Kim, S., Lee, SW., Koh, JY., et al.[2023]

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]

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]

IL-7 plays a crucial role in regulating B-cell development by suppressing premature Ig light-chain rearrangement, which is essential for proper antibody formation.

In a study examining human CD19⁺ cells in xenogeneic cultures, it was found that less than 10% of these cells had complete IGH rearrangements, indicating that IL-7 signaling is vital for the correct timing of immunoglobulin gene rearrangement during B-cell maturation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. Nodland, SE., Berkowska, MA., Bajer, AA., et al.[2021]

A single subcutaneous dose of recombinant human IL-7 (rhIL-7) was well tolerated in HIV-infected individuals, showing biological activity at a dose of 3 microg/kg and a maximum tolerated dose of 30 microg/kg, with mild side effects like injection site reactions and transient liver function test elevations.

rhIL-7 administration led to increased numbers of circulating CD4(+) and CD8(+) T cells, indicating its potential to enhance T cell recovery in HIV infection, although it also caused transient increases in plasma HIV-RNA levels in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Sereti, I., Dunham, RM., Spritzler, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05600920

Study Details | NCT05600920 | A Single-arm, Dose ... An Open-Label, Single-Arm, Phase 1/2 Dose-Escalation Trial of Long-Acting Recombinant Human IL-7 (NT-I7, Efineptakin-Alpha) for Idiopathic CD4 Lymphopenia.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05600920/a-single-arm-dose-escalation-trial-of-long-acting-recombinant-human-il-7-nt-i7-efineptakin-alfa-for-idiopathic-cd4-lymphopenia?id=2&slug=aids-and-aids-related-infections

A Single-arm, Dose-escalation Trial of Long-acting ... Study Description: Open-label trial of efineptakin alfa (NT-I7) to manage idiopathic CD4 lymphopenia (ICL). After baseline assessments, NT-I7 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11804200/

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

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

GX-I7, a long-acting IL-7, safely and effectively increased ... GX-I7, a long-acting IL-7, safely and effectively increased peripheral CD8+/CD4+ T cells and TILs in patients with locally advanced or ...

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. niaid.nih.gov niaid.nih.gov/clinical-trials/single-arm-dose-escalation-trial-long-acting-recombinant-human-il-7-nt-i7

A Single-arm, Dose-escalation Trial of Long-acting ... The purpose of this study is to test a new drug (NT-17) in people with idiopathic CD4 lymphopenia (ICL) which can increase the number of CD4 ...

7. jitc.bmj.com jitc.bmj.com/content/13/2/e010291

Phase I study of efineptakin alfa (NT-I7) for the treatment ... We hypothesize that IL-7 treatment may be beneficial in Kaposi sarcoma (KS), where CD4+ T cell lymphopenia is associated with KS onset. There ...