Idiopathic CD4 LymphopeniaPhase 1NCT04097561
Safety of Belimumab in People With Idiopathic CD4 Lymphopenia and Autoantibodies (Phoebe)
A Phase 1 study testing Belimumab in people with Idiopathic CD4 Lymphopenia, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Idiopathic CD4 Lymphopenia
- What is being tested?
- Belimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2020to 25 Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals must meet all of the following criteria to be eligible for study participation:
- Aged 18-70 years.
- Enrolled in study 09-I-0102.
- Has a documented diagnosis of ICL, defined as the following:
- CD4 count < 300 cells/microliter in at least 2 separate measurements 6 weeks apart at any point in the past, AND
- CD4 count < 300 cells/microliter within previous 90 days.
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- Evidence for autoantibody positivity (eg, ANA or in the research flow method looking for antilymphocyte antibodies).
- Female participants of childbearing potential must agree to use adequate contraception when engaging in sexual activities that can result in pregnancy, beginning at day 0 (or day 30 for hormonal contraception) until 4 months after the last dose of belimumab.
- Acceptable methods of contraception include the following:
- Hormonal contraception.
- Male or female condom.
- Diaphragm or cervical cap with a spermicide.
- Intrauterine device.
- Able to provide informed consent.
- Willing to allow samples to be stored for future research.
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- Prior receipt of belimumab. Exception: If an individual had been previously enrolled in this study and received up to 3 doses of belimumab but had to withdraw for reasons that were not related to safety or clinical concerns, they may be re-enrolled. In this case, at least 6 months must have passed from the last prior infusion and they will restart the protocol and drug administration from the beginning.
- Allergy to any component of belimumab formulation.
- HIV infection or other recognized congenital or acquired immunodeficiency.
- Current moderate or severe acute illness (eg, febrile illness, seizure, myocardial infarction, cerebrovascular accident, pulmonary embolism) or progressive serious infection related to ICL that, in the opinion of the principal investigator, would make the participant unsuitable for the study. Pre-existing infections that have been stable both clinically and with laboratory (eg, cryptococcal antigen titer or histoplasma antigen level) and radiographic evaluations on maintenance therapy over at least a year will be eligible.
- Untreated hepatitis B or C (acute or chronic).
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- Active tuberculosis infection.
- Serum creatinine > 1.5 times the upper limit of normal (ULN).
- Hemoglobin < 8 g/dL.
- Alanine transaminase or aspartate transaminase > 2 times ULN.
- Serum IgG < 400 mg/L.
- Current use of systemic glucocorticosteroids, with the exception of corticosteroid nasal spray or inhaler and topical steroids.
- Any cancer diagnosis or autoimmune condition requiring systemic chemotherapy or immunomodulant-affecting antibody responses (eg, rituximab, ibrutinib), IV or SC Ig supplementation, radiation therapy, or any such treatment within the previous 6 months. Apremilast, Plaquenil, or nonsteroidal anti-inflammatory drugs will not be exclusionary.
- Severe depression. Psychiatry may be consulted prior to final eligibility decision.
- Infections (recently acquired or exacerbation of a chronic infection) that required new medications for management within the past 60 days.
- Receipt of any vaccination within the past 30 days.
- Pregnant.
- Breastfeeding.
- Any behavioral or substance use issue that would compromise appropriate follow up and participation in this study.
- Concomitant diagnosis of SLE will not be exclusionary. Although SLE can be associated with lymphopenia, patients with lupus and extreme lymphopenia in the absence of cytotoxic or immunosuppressive medications and history of unusual infections will be eligible if they are participants of study 09-I-0102.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Official title: A Phase 1 Evaluation of the Safety of Belimumab in People With Idiopathic CD4 Lymphopenia and Autoantibodies (Phoebe)
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.
Read more
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).
...
Read the 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 mg/kg 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.
- Conditions
- Idiopathic CD4 Lymphopenia
- Being tested
- Belimumab
- Keywords
- CD8 Counts, B-Cell Activating Factor (BAFF), Heterogeneous Disorder, Autoimmune Disease
- Medical subject headings
- T-Lymphocytopenia, Idiopathic CD4-Positive, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelimumabBiological
Belimumab 10 mg/kg once every 2 weeks for 3 doses, and then once every 4 weeks for 5 doses, delivered via 1-hour intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| Single arm, open-label | Experimental | Belimumab 10 mg/kg once every 2 weeks for 3 doses, and then once every 4 weeks for 5 doses, delivered via 1-hour intravenous (IV) infusion. Receives: Biological: Belimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (AEs) that are possibly, probably, or definitely related to belimumab.
Incidence of AEs that are possibly, probably, or definitely related to belimumab.
Measured: Week 2 through Week 48
Secondary outcomes (4)
Evaluation of CD4 and CD8 counts at all study visits.
Evaluation of CD4 and CD8 counts at all study visits.
Measured: All study visits
Evaluation of natural killer (NK) and B-cell counts at all study visits.
Evaluation of NK and B-cell counts at all study visits.
Measured: All study visits
Evaluation of serum levels of BAFF at all study visits.
Evaluation of serum levels of BAFF at all study visits.
Measured: All study visits
Evaluation of any known clinical autoimmune disease (eg, hemolytic anemia) or positive autoantibodies such as ANA at all study time points.
Evaluation of any known clinical autoimmune disease (eg, hemolytic anemia) or positive autoantibodies such as ANA at all study time points.
Measured: All study visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2019
- Study start13 Jan 2020
- Primary completion25 Mar 2027 (estimated)
- Study completion25 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic CD4 LymphopeniaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irini Sereti, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04097561
- Sponsor's protocol ID
- 190140
- Other IDs
- 19-I-0140
- Status last verified
- 17 Sep 2026
- First submitted
- 19 Sep 2019
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IPD available.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Evaluation of the Safety of Belimumab in People With Idiopathic CD4 Lymphopenia and Autoantibodies (Phoebe)
- ClinicalTrials.gov ID
- NCT04097561
- Acronym / sponsor ID
- 190140
- Conditions
- Idiopathic CD4 Lymphopenia
- Keywords
- CD8 Counts, B-Cell Activating Factor (BAFF), Heterogeneous Disorder, Autoimmune Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 25 Mar 2027 (estimated)
- Study completion
- 25 Mar 2027 (estimated)
- First posted
- 20 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
...
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 mg/kg 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm, open-label | Experimental | Biological: BelimumabBelimumab 10 mg/kg once every 2 weeks for 3 doses, and then once every 4 weeks for 5 doses, delivered via 1-hour intravenous (IV) infusion. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Individuals must meet all of the following criteria to be eligible for study participation:
- Aged 18-70 years.
- Enrolled in study 09-I-0102.
- Has a documented diagnosis of ICL, defined as the following:
- Evidence for autoantibody positivity (eg, ANA or in the research flow method looking for antilymphocyte antibodies).
Key exclusion criteria (20 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- Prior receipt of belimumab. Exception: If an individual had been previously enrolled in this study and received up to 3 doses of belimumab but had to withdraw for reasons that were not related to safety or clinical concerns, they may be re-enrolled. In this case, at least 6 months must have passed from the last prior infusion and they will restart the protocol and drug administration from the beginning.
- Allergy to any component of belimumab formulation.
- HIV infection or other recognized congenital or acquired immunodeficiency.
- Current moderate or severe acute illness (eg, febrile illness, seizure, myocardial infarction, cerebrovascular accident, pulmonary embolism) or progressive serious infection related to ICL that, in the opinion of the principal investigator, would make the participant unsuitable for the study. Pre-existing infections that have been stable both clinically and with laboratory (eg, cryptococcal antigen titer or histoplasma antigen level) and radiographic evaluations on maintenance therapy over at least a year will be eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelimumabBelimumab 10 mg/kg once every 2 weeks for 3 doses, and then once every 4 weeks for 5 doses, delivered via 1-hour intravenous (IV) infusion. | Biological | Single arm, open-label |
Primary outcome
Incidence of adverse events (AEs) that are possibly, probably, or definitely related to belimumab.
Time frame: Week 2 through Week 48
Incidence of AEs that are possibly, probably, or definitely related to belimumab.
4 secondary outcomes
Evaluation of CD4 and CD8 counts at all study visits.
Time frame: All study visits
Evaluation of natural killer (NK) and B-cell counts at all study visits.
Time frame: All study visits
Evaluation of serum levels of BAFF at all study visits.
Time frame: All study visits
Evaluation of any known clinical autoimmune disease (eg, hemolytic anemia) or positive autoantibodies such as ANA at all study time points.
Time frame: All study visits
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. There is not a plan to make IPD available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Irini Sereti, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Belimumab in people with Idiopathic CD4 Lymphopenia, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Irini Sereti, M.D. ((301) 496-5533, isereti@niaid.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (AEs) that are possibly, probably, or definitely related to belimumab. (time frame: Week 2 through Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.