Testing a new drug to increase CD4 T cells in patients with low immune cell counts

* INCLUSION CRITERIA:

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

1. Aged 18 to 75 years.
2. Able to provide informed consent.
3. Co-enrolled in NIH protocol 09-I-0102, Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia (EPIC) study (NCT0086726).
4. Documented ICL, defined as CD4 T-cell count \<300 cells/microliter in at least 2 different measurements at least 6 weeks apart, at any point in the past.
5. Participants who can become pregnant or who can impregnate their partner must agree to remain abstinent or to use 2 highly effective methods of contraception, at least 1 of which must be a barrier method, when engaging in sexual activities that can result in pregnancy, beginning at the first pre-injection visit until the 30 days after the last injection. Acceptable methods of contraception include the following:

   1. Male or female condom.
   2. Diaphragm or cervical cap with a spermicide.
   3. Hormonal contraception.
   4. Intrauterine device.

Note: Contraception requirements do not apply to participants who are post-menopause (age \>=45 years plus no menses for 12 consecutive months without an alternative medical cause).

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

1. Current moderate or severe acute illness (eg, febrile illness, seizure, myocardial infarction, cerebrovascular accident, pulmonary embolism) that in the opinion of the study team would make the individual unsuitable for the study.
2. Clinical or microbiologic evidence of active progressive cryptococcal central nervous system (CNS) disease or nontuberculous mycobacterial (NTM) infections within the last year. History of stable cryptococcal CNS disease or NTM diseases since more than 1 year can be enrolled but will need to have undetectable CSF cryptococcal antigen and initiate/maintain antifungal or antimycobacterial treatment, respectively.
3. Pregnant or breastfeeding.
4. HIV infection, chronic hepatitis B or C infection, and any other recognized congenital or acquired immunodeficiency (eg, SCID IL-2/JAK3/ADA, MAGT1, MHC1 deficiency, CVID, DOCK8).
5. Serum creatinine \>1.5 X ULN, platelets \<50,000/microliter, hemoglobin \<9 g/dL, AST/ALT\>2.5 X ULN, total bilirubin \>1.5 X ULN (except if due to Gilbert's syndrome), or immunoglobulin (Ig) G level \<450 mg/L.
6. Current (within 3 months of screening) use of systemic glucocorticosteroids or immunomodulants other than corticosteroid nasal spray or inhaler and topical steroids.
7. Any established diagnosis of autoimmune disease requiring systemic treatment except for vitiligo or endocrine disease (including diabetes, thyroid disease, and adrenal disease) controlled by replacement therapy.
8. Malignancy requiring systemic chemotherapy or immunotherapy within 2 months of screening.
9. Receipt of any other investigational agents within 3 months of screening.
10. Any condition that, in the opinion of the study team contraindicates participation in this study.

Participants will be selected in an equitable manner from the available pool of potentially eligible individuals, without regard to factors such as sex, gender, race, ethnicity, or socioeconomic status, except for age.