A Single-arm, Dose-escalation Trial of Long-acting Recombinant Human IL-7 (NT-I7, Efineptakin Alfa) for Idiopathic CD4 Lymphopenia

NCT05600920 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10000821000821-I
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Idiopathic CD4 lymphopenia (ICL) is a syndrome characterized by low levels of certain immune cells called CD4 T cells. The low CD4 T cells renders people with ICL prone to many types of severe infections, autoimmune diseases, and cancers. Although these infections and diseases can be treated whenever occur, there is currently no treatment that targeting the underlying deficiency of CD4 T cells can provide a definitive treatment for people with ICL. Objective: To test a new drug (NT-17) in people with ICL which can increase the number of CD4 T cells Eligibility: People aged 18 to 75 years with ICL who are also enrolled in NIH protocol 09-I-0102. Design: Participants will be screened. They will have a physical exam and blood tests. Some participants with high suspicion of central nervous system infection or history of such infections may also undergo a lumbar puncture. A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Participants will receive 3 doses of NT-17, each about 12 weeks apart. NT-17 is injected into the muscle of the upper arm, thigh, or buttock. They will visit the clinic 5 days before each dose and again 2 and 4 weeks after each dose. Blood will be drawn at all visits. Participants will undergo leukapheresis 3 times. Blood will be drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in the other arm. Some visits will include a rectal swab. Some participants may have additional tests, including a skin exam, skin biopsies, and medical imaging. Participants will have 3 follow-up visits every 3 months after they finish treatment.

Conditions

Idiopathic CD4 Lymphopenia

Keywords

Opportunistic Infections; Immunological Therapy; T-Cell Deficiency; Cytokine Therapy

Outcome Measures

Primary Outcomes (1)

• Number and severity of AEs possibly, probably, or definitely related to NT I7 administration evaluated at week 60 (end-of-study visit).

  Evaluate the safety (all AEs) of NT-I7 in patients with ICL.

  Week 60

Secondary Outcomes (3)

• Evaluation of the trajectory of ALC, and CD4, CD8, B, and NK counts measured at all study visits up to week 60 (end-of-study visit).

  Up to Week 60

• Evaluation of the trajectory of ALC and CD4, CD8, B, and NK counts measured at all study visits up to week 36 (interim analysis).

  Up to Week 36

• Evaluation of the trajectory of ALC and CD4, CD8, B, and NK counts measured between week 36 (12 weeks after last dose of NT-I7) and week 60.

  Up to Week 60

Study Arms (1)

Single Cohort

EXPERIMENTAL

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

Drug: Recombinant human interleukin (IL) 7-hyFc

Interventions

Recombinant human interleukin (IL) 7-hyFc DRUG

Structural Formula: NT-I7 is a fusion protein comprising human IL-7 fused to the human IgD hinge region. This in turn is fused to the N-terminal region of CH2 from IgD and two key regions of the antibody IgG4: C-terminal region of CH2 and the entire CH3 region. NT-I7 will be administered by IM injection once every 12 weeks for a total of 3 doses, with the final dose at week 24. In the absence of treatment delays due to AEs, a treatment course of 24 weeks will be pursued in all enrolled participants. The dose levels to be used in this study are 240, 480, and 720 microgram/kg. NT-I7 dosing will be determined using the weight recorded at the screening visit. The dose will be based on the participant s actual body weight, unless the participant has a BMI \>=30 kg/m2, in which case adjusted body weight will be used.

Single Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals must meet all of the following criteria to be eligible for study participation:
• Aged 18 to 75 years.
• Able to provide informed consent.
• Co-enrolled in NIH protocol 09-I-0102, Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia (EPIC) study (NCT0086726).
• Documented ICL, defined as CD4 T-cell count \<300 cells/microliter in at least 2 different measurements at least 6 weeks apart, at any point in the past.
• Participants who can become pregnant or who can impregnate their partner must agree to remain abstinent or 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 at the first pre-injection visit until the 30 days after the last injection. Acceptable methods of contraception include the following:
• Male or female condom.
• Diaphragm or cervical cap with a spermicide.
• Hormonal contraception.
• Intrauterine device.
• Note: Contraception requirements do not apply to participants who are post-menopause (age \>=45 years plus no menses for 12 consecutive months without an alternative medical cause).

You may not qualify if:

• Individuals meeting any of the following criteria will be excluded from study participation:
• Current moderate or severe acute illness (eg, febrile illness, seizure, myocardial infarction, cerebrovascular accident, pulmonary embolism) that in the opinion of the study team would make the individual unsuitable for the study.
• Clinical or microbiologic evidence of active progressive cryptococcal central nervous system (CNS) disease or nontuberculous mycobacterial (NTM) infections within the last year. History of stable cryptococcal CNS disease or NTM diseases since more than 1 year can be enrolled but will need to have undetectable CSF cryptococcal antigen and initiate/maintain antifungal or antimycobacterial treatment, respectively.
• Pregnant or breastfeeding.
• HIV infection, chronic hepatitis B or C infection, and any other recognized congenital or acquired immunodeficiency (eg, SCID IL-2/JAK3/ADA, MAGT1, MHC1 deficiency, CVID, DOCK8).
• Serum creatinine \>1.5 X ULN, platelets \<50,000/microliter, hemoglobin \<9 g/dL, AST/ALT\>2.5 X ULN, total bilirubin \>1.5 X ULN (except if due to Gilbert's syndrome), or immunoglobulin (Ig) G level \<450 mg/L.
• Current (within 3 months of screening) use of systemic glucocorticosteroids or immunomodulants other than corticosteroid nasal spray or inhaler and topical steroids.
• Any established diagnosis of autoimmune disease requiring systemic treatment except for vitiligo or endocrine disease (including diabetes, thyroid disease, and adrenal disease) controlled by replacement therapy.
• Malignancy requiring systemic chemotherapy or immunotherapy within 2 months of screening.
• 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.
• Participants will be selected in an equitable manner from the available pool of potentially eligible individuals, without regard to factors such as sex, gender, race, ethnicity, or socioeconomic status, except for age.

Sponsors & Collaborators

• NeoImmuneTech: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

T-Lymphocytopenia, Idiopathic CD4-Positive; Opportunistic Infections; Thymic aplasia

Condition Hierarchy (Ancestors)

Lymphopenia; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases; Infections

Study Officials

• Andrea Lisco, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Lisco, M.D.

CONTACT

(301) 761-7122; andrea.lisco@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 1, 2022
• Study Start: November 6, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03-05

Locations

US (1)