A Single-arm, Dose-escalation Trial of Long-acting Recombinant Human IL-7 (NT-I7, Efineptakin Alfa) for Idiopathic CD4 Lymphopenia
ClinicalTrials.gov ID NCT05600920
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institutes of Health Clinical Center (CC) (National Institute of Allergy and Infectious Diseases (NIAID)) (Responsible Party)
Last Update Posted: 2025-04-03
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.
Detailed Description
Study Description:
Open-label trial of efineptakin alfa (NT-I7) to manage idiopathic CD4 lymphopenia (ICL). After baseline assessments, NT-I7 will be administered intramuscularly (IM) at the NIH Clinical Center (CC) once every 12 weeks for 3 total doses, with the final dose at week 24, in 3 cohorts of 10 participants each. The doses for each cohort are 240, 480, or 720 microgram/kg. Blood will be drawn at each dose visit, as well as 5 days before and 14 and 30 days after each dose visit. Blood laboratory evaluations will be performed at the NIH CC or by remote laboratory providers, with results shared with the NIH study team. Primary and secondary evaluations include assessment of adverse events (AEs) and T-cell counts. Questionnaires will be administered to assess patient health perceptions and quality of life. The final study visit will be at week 60.
Primary Objective:
- Evaluate the safety (all AEs) of NT-I7 in patients with ICL.
Secondary Objective:
- Evaluate the immunologic effects of NT-I7 on peripheral CD4 T-cell counts in ICL patients.
- Evaluate the safety (study drug-related AEs) of NT-I7 in patients with ICL.
Exploratory Objectives:
- Evaluate the ability of NT-I7 to increase CD4 T-cell counts.
- Evaluate the clinical effects of NT-I7 administration in participants with treatment-refractory human papillomavirus (HPV)-related diseases.
- Evaluate the effect of NT-I7 on clinical sequelae, radiologic or laboratory findings associated with previous opportunistic infections.
- Evaluate effects of NT-I7 administration on presence/titer of clinical autoantibodies.
- Evaluate the immunogenicity of NT-I7.
- Evaluate the pharmacokinetics (PK) of NT-I7 and explore exposure-safety and exposure-efficacy relationships.
Primary Endpoint:
- Number and severity of AEs observed after NT-I7 administration evaluated at week 60 (end-of-study visit).
Secondary Endpoints:
- Evaluation of the trajectory of absolute lymphocyte count (ALC), and CD4, CD8, B, and NK counts measured at all study visits up to week 60 (end-of-study visit).
- Evaluation of the trajectory of ALC and CD4, CD8, B, and NK counts measured at all study visits up to week 36 (interim analysis).
- 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.
- Number and severity of AEs possibly, probably, or definitely related to NT-I7 administration evaluated at week 60 (end-of-study visit).
Exploratory Endpoints:
- Proportion of participants with CD4 T-cell counts >=300 cells/microliter with NT-I7 treatment evaluated at week 60 (end-of-study visit).
- Time (cumulative number of days or weeks) that participants with baseline CD4 T-cell counts <200 cells/microliter maintain CD4 T-cell counts >= 200 cells/microliter after initiating treatment with NT-I7.
- Changes in skin or mucosal manifestations of HPV diseases as evaluated by clinical photography, and dermatologic and histologic evaluation.
- Changes in the clinical, radiologic, or laboratory findings associated with previous history of opportunistic infections.
- Changes in presence and titer of clinical autoantibodies.
- Incidence of antidrug antibodies (ADA) to NT-I7 in the study population.
- Serum concentration of NT-I7 administered at specified timepoints for the maximum observed concentration (Cmax).