Ignite Creation Date:
2024-05-06 @ 6:16 PM
Last Modification Date:
2024-10-26 @ 2:44 PM
Study NCT ID:
NCT05600920
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2022-10-27
Brief Title:
A Single-arm Dose-escalation Trial of Long-acting Recombinant Human IL-7 NT-I7 Efineptakin Alfa for Idiopathic CD4 Lymphopenia
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Open-Label Single-Arm Phase 12 Dose-Escalation Trial of Long-Acting Recombinant Human IL-7 NT-I7 Efineptakin-Alpha for Idiopathic CD4 Lymphopenia
Status:
RECRUITING
Status Verified Date:
2024-10-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 microgramkg 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 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
1 Evaluate the immunologic effects of NT-I7 on peripheral CD4 T-cell counts in ICL patients
2 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 presencetiter 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 cellsmicroliter 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 cellsmicroliter maintain CD4 T-cell counts 200 cellsmicroliter 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
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 microgramkg 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 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
1 Evaluate the immunologic effects of NT-I7 on peripheral CD4 T-cell counts in ICL patients
2 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 presencetiter 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 cellsmicroliter 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 cellsmicroliter maintain CD4 T-cell counts 200 cellsmicroliter 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 000821-I | None | None | None |