A Single Dose of Pembrolizumab in HIV-Infected People

• Status: Recruiting
• Trial end date: 2022-11-20
• Target enrollment: 0
• Participant gender: All

Summary

Background:

Human immunodeficiency virus (HIV) attacks the immune system. Some people with HIV have a low CD4+ T-cell count despite taking antiviral medicines that control HIV replication. These cells fight disease, so a low count makes it easier for people to become sick. Researchers want to see if a new drug can improve the immune system, including T cells. The drug is called pembrolizumab

Objective:

To see if pembrolizumab is safe to use in people with HIV who have a low CD4+ T cell count despite taking medcines that control HIV replication, and to see if it strengthens the immune system.

Eligibility:

People age 18 years or older with HIV who are taking antiretroviral drugs as treatment, have blood HIV levels below detection limits of commercial assays, and have a low CD4+ T-cell count (below 350 cells/mm3).

Design:

Participants will be screened with:

Medical history

Physical exam

Heart, blood, and urine tests

Sexually active participants must use 2 kinds of birth control.

Participants will have leukapheresis. Blood will be removed through a needle in one arm. A machine will remove white blood cells. The rest of the blood will be returned into the other arm.

Participants will have a baseline visit. They will have blood tests. They may have a pregnancy test.

A needle will insert a thin plastic tube (IV) into an arm vein. The participants will get the study drug or a placebo through the IV for 30 minutes. They will be watched for a couple hours after.

Participants will have 11 follow-up visits over the next 48 weeks. They will have a physical exam, vital signs, medical review, and blood tests.

Participants may have another leukapheresis.

Participants will be called every 12 weeks after their last follow-up visit to talk about how they feel and their health. Participation ends after the week 96 phone call.

...

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Treatments: Pembrolizumab

Criteria

• INCLUSION CRITERIA:

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

1. Greater than or equal to 18 years of age.

2. Documented HIV-1 infection (eg, positive standard enzyme-linked immunosorbent assay or rapid HIV-1/HIV-2 antibody test with a confirmatory test such as western blot, or documentation of repeated HIV RNA of greater than 1000 copies/mL). Outside documentation will be acceptable.

3. Absolute neutrophil count greater than 1000/microL.

4. Platelet count greater than 125,000/microL.

5. Hemoglobin greater than 10 g/dL.

6. Aspartate transaminase (AST) and alanine transaminase (ALT) less than 1.5 times the upper limit of normal (ULN). Total bilirubin less than 1.1 x ULN (unless participant is taking atazanavir or has Gilbert syndrome).

7. Calculated creatinine clearance (estimated glomerular filtration rate) greater than or equal to 60 mL/min/1.73 m^2.

8. Thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) within normal limits. If TSH is not within normal limits then the participant may be eligible if thyroxine (T4) is within normal limits. Participants will not be excluded if they are on a stable dose of replacement thyroid medication; dose may be adjusted as needed.

9. No significant underlying pulmonary, cardiac, renal, or hepatic disease, as defined by a need for drug treatment or ongoing physician care.

10. Under the care of a primary care physician.

11. Willing to comply with study requirements and procedures including storage of biological specimens for future use in medical research.

12. Willing to allow genetic testing.

13. Able to provide informed consent.

14. Participants of reproductive potential must agree to not become pregnant or to impregnate a partner beginning 30 days before the dose of pembrolizumab through 120 days postdose. Non-reproductive potential is defined as azoospermia, postmenopausal, surgical sterilization at least 6 weeks before screening, or a congenital or acquired condition that definitively prevents conception. Further, postmenopausal is defined as at least 12 consecutive months with no menses at age 50 or older, and also a high follicle-stimulating hormone level in postmenopausal range at ages 45-50 years, for participants not using hormonal contraception or hormone replacement therapy.

Participants of reproductive potential must either practice complete and uninterrupted abstinence from heterosexual activity or use two of the following methods of contraception with their partners. The 2 methods must include one from each group, both of which must be consistently use:

• Barrier methods:

• a. Diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide).

• b. Cervical cap with spermicide (only for nulliparous partners).

• c. Contraceptive sponge (only for nulliparous partners).

• d. Male or female condom (cannot be used together).

• Non-barrier methods:

• a. Intrauterine device.

• b. Hormonal contraception: pill (estrogen/progestin or progestin-only), skin patch, vaginal ring, rod implanted in the skin, or subcutaneous injection.

15. Participants must meet criteria for INR, defined as follows:

• a. Has been on a cART regimen for at least 12 months and on a stable regimen for at least 4 weeks.

• b. Has evidence of viral suppression, defined as viral load less than 40 copies/mL, and documented suppression for at least 12 months prior to screening. A viral load of less than 500 copies/mL once in the year preceding screening will be allowed if there is documentation of a viral load less than 40 copies/mL on subsequent testing and at screening.

• c. CD4+ T-cell count greater than 100 cells/mm^3 and less than or equal to 350 cells/mm^3.

EXCLUSION CRITERIA:

1. Has used an investigational drug agent or investigational device within 12 weeks of baseline. However, ARVs obtained through expanded access programs are permitted.

2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

3. Known allergy to any component of the pembrolizumab formulation.

4. Systemic steroid therapy or other immunosuppressive therapy in the 3 months prior to enrollment. (Inhaled or topical corticosteroids are permitted.)

5. Has used an immunotherapeutic agent (eg, cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, sirolimus, therapies targeting tumor necrosis factor- ) within 6 months of baseline necrolysis. Replacement therapy (eg, T4.) is not considered a form of systemic treatment.

6. Has received any vaccine, live or inactivated, within 30 days of baseline, or plans to receive any vaccine within 16 weeks of receiving pembrolizumab.

7. Has active autoimmune disease or a history of autoimmune disease that has required systemic treatment (eg, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Such autoimmune diseases include for example psoriasis, systemic lupus erythematosus, autoimmune uveitis, autoimmune hepatitis, inflammatory colitis, rheumatoid arthritis, Guillain-Barr(SqrRoot)(Copyright) syndrome, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Replacement therapy (eg, T4.) is not considered a form of systemic

treatment.

8. Has known history of, or any evidence of active, non-infectious pneumonitis.

9. Malignancy requiring systemic therapy, or a history of malignancy that required systemic therapy within the past 5 years. However, cutaneous basal cell carcinoma or cutaneous Kaposi sarcoma not requiring systemic therapy will not be exclusionary.

10. Has known active hepatitis B (HBV) or potential for HBV reactivation (eg, hepatitis B surface antigen [HBS] reactive, HBV DNA positive, or isolated anti-core antibody positive; individuals who are anti-HBS antibody positive with or without anti-core Ab are eligible).

11. Has known active hepatitis C (HCV; eg, HCV RNA [qualitative] is detected). Patients who have sustained virologic response (SVR) to anti-HCV treatment are eligible if at least 24 weeks have passed since achieving SVR.

12. Females who are pregnant, planning to become pregnant, or are breastfeeding..

13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

14. History or other clinical evidence of:

• a. Significant or unstable cardiac disease (eg, angina, congestive heart failure, myocardial infarction).

• b. Significant pulmonary disease (eg, chronic obstructive pulmonary disease, asthma requiring systemic therapy).

• c. Severe illness, chronic liver disease, malignancy, immunodeficiency other than HIV, active systemic infection (other than HIV) requiring therapy.

15. Opportunistic infection requiring maintenance therapy, including toxoplasmosis, fungal infections other than candida (eg, cryptococcosis, histoplasmosis, coccidioidomycosis), atypical mycobacterial infection. Secondary Pneumocystis, candida, and HSV prophylaxis will be permitted.

16. Active or history of tuberculosis (TB), or positive TB QuantiFERON Gold test.

17. Known osteoporosis or diabetes mellitus.

18. Hemoglobin A1c greater than 6%.

19. Fasting triglyceride greater than 300 mg/dL.

20. Any condition that, in the opinion of the investigator, would make the participant unsuitable for the study.