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

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called NT-17 in people with idiopathic CD4 lymphopenia (ICL), a condition with low levels of important immune cells. The drug aims to increase these immune cells to help protect against infections and diseases. Participants will receive multiple doses of NT-17 and be monitored for safety and effectiveness.

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.

What data supports the effectiveness of the drug NT-I7 for treating Idiopathic CD4 Lymphopenia?

Research shows that NT-I7, a form of interleukin-7, can increase the number of CD4 and CD8 T cells, which are important for immune function. This has been observed in studies involving healthy adults and HIV-infected patients, suggesting its potential to help people with low T-cell counts, like those with Idiopathic CD4 Lymphopenia. ^{1 2 3 4 5}

Is NT-I7 safe for humans?

NT-I7, also known as hIL-7-hyFc, has been tested in humans and was generally well-tolerated, with the most common side effect being mild injection site reactions that resolved on their own. In studies with healthy volunteers and HIV-infected individuals, it showed a good safety profile, although some transient liver function changes and increases in HIV-RNA levels were noted in a few cases. ^{1 4 5 6 7}

How is the drug NT-I7 different from other treatments for Idiopathic CD4 Lymphopenia?

NT-I7 is unique because it is a long-acting form of interleukin-7 (IL-7) fused with a hybrid Fc, which helps increase T-cell counts and improve immune function. Unlike other treatments, it is specifically designed to enhance T-cell proliferation and persistence, making it a promising option for patients with compromised T-cell immunity. ^{1 5 6 8 9}

Research Team

Andrea Lisco, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

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

I am between 18 and 75 years old.

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

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. [2023]

2. United States 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. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. [2021]

5. Australia pubmed.ncbi.nlm.nih.gov

Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. [2021]

7. United States 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

IL-7 and lymphopenia. [2016]