Ignite Creation Date:
2024-05-06 @ 1:41 PM
Last Modification Date:
2024-10-26 @ 1:18 PM
Study NCT ID:
NCT04097561
Status:
RECRUITING
Last Update Posted:
2024-06-25
First Post:
2019-09-19
Brief Title:
Safety of Belimumab in People With Idiopathic CD4 Lymphopenia and Autoantibodies Phoebe
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase 1 Evaluation of the Safety of Belimumab in People With Idiopathic CD4 Lymphopenia and Autoantibodies Phoebe
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
People with Idiopathic CD4 lymphopenia ICL have lower numbers of a type of white blood cell called CD4 cells White blood cells fight against infections Low levels of CD4 cells may make a person more likely to get sick There are no approved treatments for ICL Researchers think a drug called belimumab may be able to help in specific situations
Objective
To see if belimumab is safe for people with ICL
Eligibility
People ages 18-70 who have ICL and are participating in NIH protocol 09-I-0102 EPIC
Design
Participants will be screened with
Medical and medication history
Physical exam
Questionnaire about mental health and depression
Blood and urine tests
Participants will have a baseline visit This will include some repeats of the screening tests They may also have leukapheresis Blood will be taken from a needle in one arm and passed through a machine that separates out the white blood cells The rest of the blood will be returned through a needle in the other arm
Participants will receive 8 doses of belimumab through IV A needle will insert a thin plastic tube into an arm vein Belimumab will be given through the IV line The first 3 doses will be given every 2 weeks The other 5 will be given once every 4 weeks Participants will have a physical exam and blood and urine tests at each dosing visit They will be monitored for up to 4 hours after the infusion
Participants will have 3 follow-up visits at around 8 16 and 24 weeks after the last dose of belimumab They will have a physical exam and blood and urine tests Once they finish this protocol and they will continue to be followed under 09-I-0102 EPIC study
People with Idiopathic CD4 lymphopenia ICL have lower numbers of a type of white blood cell called CD4 cells White blood cells fight against infections Low levels of CD4 cells may make a person more likely to get sick There are no approved treatments for ICL Researchers think a drug called belimumab may be able to help in specific situations
Objective
To see if belimumab is safe for people with ICL
Eligibility
People ages 18-70 who have ICL and are participating in NIH protocol 09-I-0102 EPIC
Design
Participants will be screened with
Medical and medication history
Physical exam
Questionnaire about mental health and depression
Blood and urine tests
Participants will have a baseline visit This will include some repeats of the screening tests They may also have leukapheresis Blood will be taken from a needle in one arm and passed through a machine that separates out the white blood cells The rest of the blood will be returned through a needle in the other arm
Participants will receive 8 doses of belimumab through IV A needle will insert a thin plastic tube into an arm vein Belimumab will be given through the IV line The first 3 doses will be given every 2 weeks The other 5 will be given once every 4 weeks Participants will have a physical exam and blood and urine tests at each dosing visit They will be monitored for up to 4 hours after the infusion
Participants will have 3 follow-up visits at around 8 16 and 24 weeks after the last dose of belimumab They will have a physical exam and blood and urine tests Once they finish this protocol and they will continue to be followed under 09-I-0102 EPIC study
Detailed Description:
Idiopathic CD4 lymphopenia ICL is characterized by persistent low CD4 counts frequently in combination with CD8 natural killer or B cell lymphopenia It is considered a heterogeneous disorder with manifestations that can include autoimmunity invasive fungal infections or infections with human papillomavirus and malignancies typically related to infections The exact etiology of ICL remains unclear and there is no specific treatment
Recent data from our group revealed a high prevalence of antilymphocyte antibodies in many of the ICL patients evaluated The targets of these antibodies remain unknown and are being investigated On some occasions these antibodies have the ability to cause antibody-dependent cytotoxicity or complement activation both mechanisms that can cause cell death Although it is unclear if these antibodies are the cause or perhaps more likely the effect of lymphopenia it is plausible they play a significant pathogenic role and at a minimum may be hampering lymphocyte compensatory mechanisms for expansion and improved survival
The immune deficiency and the unclear role of autoantibodies preclude aggressive immunosuppressive treatment eg corticosteroids for ICL Therefore a rational approach to treatment is belimumab a monoclonal antibody that targets Blys also call BAFF for B-cell activating factor expressed on activated B cells and plasma cells Belimumab is approved by the United States Food and Drug Administration FDA for patients with systemic lupus erythematosus SLE who have evidence of autoantibodies and has shown efficacy in both reducing symptoms and leading to a modest decrease in autoantibodies
In this open-label prospective single-arm study ICL patients with laboratory evidence of antilymphocyte antibodies will be recruited Belimumab will be administered by intravenous infusion for 6 months with an extended follow-up of an additional 6 months Administration of the study drug will follow the SLE scheme of 10 mgkg at study entry 2 weeks 4 weeks and monthly thereafter 8 doses total Three additional visits approximately every 2 months will complete the 52-week study Clinical safety evaluations with immunologic and serologic testing will be performed at all study visits
This protocol will assess the safety of belimumab in ICL and also help in better understanding the role of autoantibodies in ICL pathogenesis This knowledge could substantially improve rationale and design of novel therapeutic interventions in ICL
Recent data from our group revealed a high prevalence of antilymphocyte antibodies in many of the ICL patients evaluated The targets of these antibodies remain unknown and are being investigated On some occasions these antibodies have the ability to cause antibody-dependent cytotoxicity or complement activation both mechanisms that can cause cell death Although it is unclear if these antibodies are the cause or perhaps more likely the effect of lymphopenia it is plausible they play a significant pathogenic role and at a minimum may be hampering lymphocyte compensatory mechanisms for expansion and improved survival
The immune deficiency and the unclear role of autoantibodies preclude aggressive immunosuppressive treatment eg corticosteroids for ICL Therefore a rational approach to treatment is belimumab a monoclonal antibody that targets Blys also call BAFF for B-cell activating factor expressed on activated B cells and plasma cells Belimumab is approved by the United States Food and Drug Administration FDA for patients with systemic lupus erythematosus SLE who have evidence of autoantibodies and has shown efficacy in both reducing symptoms and leading to a modest decrease in autoantibodies
In this open-label prospective single-arm study ICL patients with laboratory evidence of antilymphocyte antibodies will be recruited Belimumab will be administered by intravenous infusion for 6 months with an extended follow-up of an additional 6 months Administration of the study drug will follow the SLE scheme of 10 mgkg at study entry 2 weeks 4 weeks and monthly thereafter 8 doses total Three additional visits approximately every 2 months will complete the 52-week study Clinical safety evaluations with immunologic and serologic testing will be performed at all study visits
This protocol will assess the safety of belimumab in ICL and also help in better understanding the role of autoantibodies in ICL pathogenesis This knowledge could substantially improve rationale and design of novel therapeutic interventions in ICL
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 |
|---|---|---|---|
| 19-I-0140 | None | None | None |