NT-I7 for Idiopathic CD4 Lymphopenia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Approved in 2 Jurisdictions
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.
12345Is 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.
14567How 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.
15689Eligibility 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
+2 more
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
+7 more
Trial 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)
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Single CohortExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Institute of Allergy and Infectious Diseases (NIAID)Lead Sponsor
NeoImmuneTechIndustry Sponsor
NeoImmune TechCollaborator
References
A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. [2023]Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity.
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]Phase I/II studies in human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy have shown that a single cycle of 3 weekly subcutaneous (s/c) injections of recombinant human interleukin 7 (r-hIL-7) is safe and improves immune CD4 T-cell restoration. Herein, we report data from 2 phase II trials evaluating the effect of repeated cycles of r-hIL-7 (20 µg/kg) with the objective of restoring a sustained CD4 T-cell count >500 cells/µL.
A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions. [2023]Interleukin-7 (IL-7) is an essential cytokine for T-cell homeostatic proliferation and maintenance. Clinical studies have shown the potential benefits of IL-7 therapy in various diseases associated with lymphopenia. However, the kinetics of the T-cell response to a single administration of IL-7 in humans have not been fully elucidated. Here, we investigated the effects of Fc-fused long-acting recombinant human IL-7 (hIL-7-hyFc, efineptakin alfa) on lymphocytes in healthy adults after a single subcutaneous or intramuscular administration. Administration of hIL-7-hyFc increased the CD8+ and CD4+ T-cell numbers up to 2.5-fold, with corresponding upregulation of Ki-67 and Bcl-2 expression, peaking at day 3 or 7. Regulatory T cells (Tregs) did not expand. Among CD8+ and CD4+ T cells, all T-cell subsets (TN, TEM, TCM, TEMRA, and TSCM) increased for 56 days. The T-cell receptor repertoire diversity of naive CD8+ and CD4+ T cells was increased by hIL-7-hyFc, whereas the memory T-cell subsets did not differ between day 56 and day 0. Transcriptomic analysis revealed that hIL-7-hyFc induced robust T-cell expansion without changes in gene expression profiles associated with T-cell functions or genes related to T-cell exhaustion, senescence, and anergy. The effector functions of antigen-specific CD8+ T cells were preserved after hIL-7-hyFc administration. Our results suggest that hIL-7-hyFc administration induced a sustained increase in the numbers of CD8+ and CD4+ T cells, but not Tregs, without qualitative changes. These results support the potential of hIL-7-hyFc as a treatment for patients with compromised T-cell immunity or as a vaccine adjuvant.
IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. [2021]Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in thymopoiesis and in peripheral expansion and survival of T lymphocytes. The safety and activity of recombinant human IL-7 (rhIL-7) administration were therefore examined in HIV-infected persons. In this prospective randomized placebo-controlled study, a single subcutaneous dose of rhIL-7 was well tolerated with biologic activity demonstrable at 3 microg/kg and a maximum tolerated dose of 30 microg/kg. Injection site reactions and transient elevations of liver function tests were the most notable side effects. Transient increases in plasma HIV-RNA levels were observed in 6 of 11 IL-7-treated patients. Recombinant hIL-7 induced CD4 and CD8 T cells to enter cell cycle; cell-cycle entry was also confirmed in antigen-specific CD8 T cells. Administration of rhIL-7 led to transient down-regulation of the IL-7 receptor alpha chain (CD127) in both CD4(+) and CD8(+) T cells. Single-dose rhIL-7 increased the numbers of circulating CD4(+) and CD8(+) T cells, predominantly of central memory phenotype. The frequency of CD4(+) T cells with a regulatory T-cell phenotype (CD25(high) CD127(low)) did not change after rhIL-7 administration. Thus, rhIL-7 has a biologic and toxicity profile suggesting a potential for therapeutic trials in HIV infection and other settings of lymphopenia. This clinical trial has been registered at http://www.clinicaltrials.gov under NCT0099671.
Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. [2022]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Emerging oncotherapeutic strategies require the induction of an immunostimulatory tumor microenvironment (TME) containing numerous tumor-reactive CD8+ T cells. Interleukin-7 (IL-7), a T-cell homeostatic cytokine, induces an antitumor response; however, the detailed mechanisms underlying the contributions of the IL-7 to TME remain unclear. Here, we aimed to investigate the mechanism underlying the induction of antitumor response by hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) through regulation of both adaptive and innate immune cells in the TME.
hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. [2021]A low lymphocyte count puts immune-compromised patients at risk of mortality. hIL-7-hyFc is a homodimeric interleukin-7 (IL-7), a potent T-cell amplifier, fused to the hybridizing IgD/IgG4 immunoglobulin domain. We performed a randomized, double-blind, placebo-controlled, dose-escalation, phase I study to assess the pharmacokinetic, pharmacodynamic, safety, tolerability, and immunogenicity profiles of hIL-7-hyFc administered s.c. and i.m. to healthy volunteers. Thirty subjects randomly received hIL-7-hyFc or its matching placebo in an 8:2 ratio at 20, 60 μg/kg s.c., or 60 μg/kg i.m. The hIL-7-hyFc was slowly absorbed and its terminal half-life was 63.26 hours after i.m. administration. The hIL-7-hyFc increased absolute lymphocyte count, mostly in T-cells, which peaked 3 weeks after administration and then lasted for several additional weeks. The hIL-7-hyFc was well-tolerated after a single s.c. and i.m. administration. Injection site reaction was the most common treatment-emergent adverse event, which resolved spontaneously without treatment. The hIL-7-hyFc can be developed into a beneficial treatment option for patients with compromised T-cell immunity. This trial was registered at www.clinicaltrials.gov as #NCT02860715.
Intravenous injection of a novel viral immunotherapy encoding human interleukin-7 in nonhuman primates is safe and increases absolute lymphocyte count. [2023]Persistence of an immunosuppression, affecting both the innate and adaptive arms of the immune system, plays a role in sepsis patients' morbidity and late mortality pointing to the need for broad and effective immune interventions. MVA-hIL-7-Fc is a non-replicative recombinant Modified Vaccinia virus Ankara encoding the human interleukin-7 fused to human IgG2 Fc fragment. We have shown in murine sepsis models the capacity of this new virotherapy to stimulate both arms of the immune system and increase survival. Herein, an exploratory study in nonhuman primates was performed following a single intravenous injection of the MVA-hIL-7-Fc used at the clinical dose to assess its safety and biological activities. Four cynomolgus macaques were followed for 3 weeks post-injection (p.i), without observed acute adverse reactions. Circulating hIL-7-Fc was detected during the first 3-5 days p.i with a detection peaking at 12 h p.i. IL-7 receptor engagement and downstream signal transduction were detected in T cells demonstrating functionality of the expressed IL-7. Expansion of blood lymphocytes, mainly CD4 and CD8 naïve and central memory T cells, was observed on day 7 p.i. together with a transient increase of Ki67 expression on T lymphocytes. In addition, we observed an increase in circulating B and NK cells as well as monocytes were albeit with different kinetics and levels. This study indicates that a vectorized IL-7-Fc, injected by intravenous route at a relevant clinical dose in a large animal model, is active without adverse reactions supporting the clinical development of this novel virotherapy for treatment of sepsis patients.
IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. [2021]IL-7 is an important cytokine for lymphocyte differentiation. Similar to what occurs in vivo, human CD19⁺ cells developing in human/murine xenogeneic cultures show differential expression of the IL-7 receptor α (IL-7Rα) chain (CD127). We now describe the relationship between CD127 expression/signaling and Ig gene rearrangement. In the present study,
IL-7 and lymphopenia. [2016]Interleukin-7 (IL-7) is a growth and anti-apoptotic factor for T-lymphocytes, with potential for clinical use in the treatment of immunodeficiencies due to loss of T-cells. Lymphopenia induced by disease (HIV infection, hemodialysis or Idiopathic CD4+ lymphopenia) or by treatment (high dose chemotherapy or depleting antibodies) for cancer or auto-immune diseases results in increased circulating levels of IL-7 which decline with T-cell recovery, however, the mechanism of such response remains to be elucidated. Furthermore, IL-7 is a major player in the regulation of peripheral T-cell homeostasis and as such is an important candidate cytokine for therapy aimed at improving T-cell reconstitution following lymphopenia. Anti- IL-7 is on the other hand proposed to treat conditions where IL-7 may play a more direct role in pathogenesis such as autoimmune disease like Rheumatoid Arthritis, Multiple Sclerosis or Inflammatory Bowel disease.