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Protocol Details

Phase 1/2 Randomized, Double-Blind, Placebo-Controlled Study of Safety and Efficacy of Abatacept for Treating Chronic Cytopenia in Cytotoxic T-lymphocyte Antigen 4 (CTLA4) Haploinsufficiency

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 8 Years
Max Age: 65 Years

Referral Letter Required


Population Exclusion(s)



Regulatory T Cells;
T-cell hyperactivation;
Autoimmune Cytopenia;
Adult Rheumatoid Arthritis;
Juvenile Idiopathic Arthritis

Recruitment Keyword(s)



CTLA4 haploinsufficency;
chronic cytopenia

Investigational Drug(s)


Investigational Device(s)



Drug: abatacept
Other: Placebo

Supporting Site

National Institute of Allergy and Infectious Diseases


CTLA4 stands for cytotoxic T-lymphocyte antigen-4. It is a protein the body makes naturally to check its immune system from attacking itself. Some people don t produce enough CTLA4 protein, causing problems due to overactive immune system such as big spleens, repeated lung infections, breathing problems, stomach and intestine symptoms as well as inflamed brain and nerve problems. Many have problems with their bone marrow causing low numbers of blood cells like platelets, red blood cells or white blood cells, which is called cytopenia. Researchers want to see if the drug abatacept can treat cytopenias by replacing the missing protein CTLA4.


To see if abatacept is safe and helps treat cytopenias caused by CTLA4 deficiency.


People ages 8-65 years who have CTLA4 deficiency with cytopenia


Participants will be screened with medical history, medication review, physical exam and blood and urine tests. They will continue their current medications and may start taking antibiotics daily. Participants will receive either abatacept or placebo through a vein for 6 months. The study team will not know if you are receiving the study drug or the placebo

Women who can become pregnant must agree to use birth control measures.

Men who get someone pregnant during the study will be asked to collect information and have the partner contact the study team.

Participants will undergo the following procedures before starting the study and at the completion:

- radiology scans of body and brain

- heart and lung function tests

- Bone marrow examination by a needle inserted into the hip bone to remove a small amount of tissue to study.

- Participants may have a small camera on a long, thin tool passed down the throat into the stomach and small intestine for evaluation of their gut.

-Questionnaires about their disease, symptoms and quality of life

Over 6 months, participants will have regular study visits and get 8 doses of the study drug or a placebo by intravenous injection. They will repeat some of the same tests done earlier at the end of the study at assess response.

About 1 month after the last study drug visit, participants will have a final study visit.

Some participants may join a treatment extension for the study drug abatacept with no placebo. They will sign a separate consent form for this.

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

1. Age 8-65 years.

2. Documented CTLA4 mutation (requires documentation of confirmed mutation via Sanger sequencing at a laboratory approved by the Clinical Laboratory Improvement Amendments [CLIA]).

3. At least one of the following established hematologic abnormalities during the past 6 months (including results from outside CLIA-certified laboratories) prior to screening:

-ANC < 750 cells/microL.

-Platelet count < 75,000 cells/microL.

-Hemoglobin < 7.5 g/dL.

4. The above mentioned hematologic abnormalities should require active treatment with steroids, immunomodulatory agents (e.g., mycophenolate mofetil, cyclosporine, tacrolimus, mercaptopurine, methotrexate, sirolimus, high dose intravenous immunoglobulin [IVIG]), and/or other agents (e.g., TPO agonists) for at least 60 days prior to screening.

5. The dose of any concomitant medication(s) aimed at treating cytopenia should be stable in the 60 days prior to screening. Stable is defined as:

-No new concomitant medications for cytopenia were initiated.

-No dose increase of the medication was required.

6. Did not receive blood product transfusions within 30 days prior to screening.

7. Did not receive abatacept within 60 days prior to screening.

8. Did not receive rituximab within 3060 days of screening.

9. Did not receive alemtuzumab at any time.

10. Has access to healthcare provider at home.

11. Able to provide informed consent.

12. Willing to allow storage of biological specimens for future use in medical research.

13. Females of childbearing potential must agree to use appropriate birth control methods when engaging in sexual activities that can result in pregnancy, beginning Day -30 through 30 days after the last dose of study agent. Appropriate methods should include 2 forms of contraception, one from each of the following categories:

-Hormonal contraception or placement of an intrauterine device or intrauterine system.

-Barrier method: Condom or occlusive cap (diaphragm or cervical/vault cap) with a spermicide.


Patients meeting any of the following criteria are not eligible for this study:

1. History of hypersensitivity to abatacept.

2. Any live vaccines (including attenuated live vaccines) within 6 weeks of screening.

3. History of acquired immunodeficiency diseases, including a positive HIV polymerase chain reaction (PCR) test result.

4. Untreated chronic hepatitis B (positive PCR) or hepatitis C (positive PCR) infection. Patients with chronic hepatitis must be on medical treatment for at least 3 months before screening and have evidence of decreased viral loads after starting treatment.

5. EBV viral load > 4log on 2 or more laboratory checks greater than 1 month apart and within 6 months of screening.

6. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of evidence of local recurrence or metastases.

7. Current active infectious disease (bacterial or fungal) including evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON TB-Gold test. Test results within the past 6 months will be accepted. If presence of latent TB is established, then treatment must be completed before the patient can be considered for enrollment. The patient may also be considered for enrollment after completing treatment of any other active bacterial or fungal infection.

8. Contraindication to PFT or CT scan.

9. Pregnancy or breastfeeding.

10. Any condition that, in the opinion of the investigator, contraindicates participation in this study.

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Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, Zhang Y, Liu Z, Fritz JM, Marsh R, Husami A, Kissell D, Nortman S, Chaturvedi V, Haines H, Young LR, Mo J, Filipovich AH, Bleesing JJ, Mustillo P, Stephens M, Rueda CM, Chougnet CA, Hoebe K, McElwee J, Hughes JD, Karakoc-Aydiner E, Matthews HF, Price S, Su HC, Rao VK, Lenardo MJ, Jordan MB. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015 Jul 24;349(6246):436-40. doi: 10.1126/science.aaa1663.

Lee S, Moon JS, Lee CR, Kim HE, Baek SM, Hwang S, Kang GH, Seo JK, Shin CH, Kang HJ, Ko JS, Park SG, Choi M. Abatacept alleviates severe autoimmune symptoms in a patient carrying a de novo variant in CTLA-4. J Allergy Clin Immunol. 2016 Jan;137(1):327-330. doi: 10.1016/j.jaci.2015.08.036. Epub 2015 Oct 21.

Salman J, Ius F, Knoefel AK, Sommer W, Siemeni T, Kuehn C, Tudorache I, Avsar M, Nakagiri T, Preissler G, Hatz R, Greer M, Welte T, Haverich A, Warnecke G. Association of Higher CD4<sup>+</sup> CD25<sup>high</sup> CD127<sup>low</sup> , FoxP3<sup>+</sup> , and IL-2<sup>+</sup> T Cell Frequencies Early After Lung Transplantation With Less Chronic Lung Allograft Dysfunction at Two Years. Am J Transplant. 2017 Jun;17(6):1637-1648. doi: 10.1111/ajt.14148. Epub 2017 Jan 24. PMID: 27931084.

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Principal Investigator

Referral Contact

For more information:

Gulbu Uzel, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
(301) 451-9035

Katherine N. Howe, P.A.-C
National Institute of Allergy and Infectious Diseases (NIAID)
(240) 669-2747

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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