Testing a new drug to increase CD4 T cells in patients with low immune cell counts

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

This study is testing a new drug to see if it can safely boost immune cell levels in people with low CD4 T cell counts due to idiopathic CD4 lymphopenia.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05600920 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a new drug, NT-I7 (efineptakin alfa), in individuals with idiopathic CD4 lymphopenia (ICL), a condition characterized by low CD4 T cell counts. Participants aged 18 to 75 will receive intramuscular injections of NT-I7 every 12 weeks for a total of three doses, with assessments of T cell counts and adverse events conducted throughout the study. The trial aims to determine whether NT-I7 can safely increase CD4 T cell levels and improve immune function in patients with ICL. Blood tests and evaluations will be performed at various intervals to monitor the drug's effects and safety.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 18 to 75 with documented idiopathic CD4 lymphopenia and enrolled in a related NIH protocol.

Not a fit: Patients with CD4 T cell counts above 300 cells/microliter or those not enrolled in the specified NIH protocol may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve immune function and reduce the risk of infections and diseases in patients with ICL.

How similar studies have performed: While the approach of using NT-I7 is novel, similar immunological therapies have shown promise in enhancing T cell counts in other conditions.

Eligibility criteria

* INCLUSION CRITERIA:

Individuals must meet all of the following criteria to be eligible for study participation:

1. Aged 18 to 75 years.
2. Able to provide informed consent.
3. Co-enrolled in NIH protocol 09-I-0102, Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia (EPIC) study (NCT0086726).
4. 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.
5. 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:

   1. Male or female condom.
   2. Diaphragm or cervical cap with a spermicide.
   3. Hormonal contraception.
   4. 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).

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

1. 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.
2. 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.
3. Pregnant or breastfeeding.
4. 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).
5. 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.
6. Current (within 3 months of screening) use of systemic glucocorticosteroids or immunomodulants other than corticosteroid nasal spray or inhaler and topical steroids.
7. 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.
8. Malignancy requiring systemic chemotherapy or immunotherapy within 2 months of screening.
9. Receipt of any other investigational agents within 3 months of screening.
10. 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.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Andrea Lisco, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Andrea Lisco, M.D.

Conditions Idiopathic CD4 Lymphopenia; Opportunistic Infections; Immunological Therapy; T-Cell Deficiency; Cytokine Therapy