A Single Dose of Pembrolizumab in HIV-Infected People
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|ClinicalTrials.gov Identifier: NCT03367754|
Recruitment Status : Recruiting
First Posted : December 11, 2017
Last Update Posted : June 21, 2018
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
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.
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).
Participants will be screened with:
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.
Sponsoring Institute: National Institute of Health Clinical Center
|Condition or disease||Intervention/treatment||Phase|
|Human Immunodeficiency Virus||Other: Placebo Drug: Pembrolizumab||Phase 1|
Expanded Access : National Institutes of Health Clinical Center (CC) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
A subset of HIV-infected patients, those with poor immunologic response to combined antiretroviral therapy (CD4+ T-cell count of less than 300-350 cells/mm^3) despite control of viremia, are at increased risk for both HIV-related and non-HIV-related complications compared to immunologic responders. Thus, novel approaches for treating HIV infection are needed to facilitate management of this patient population.
One potential drug target for HIV treatment is the T-cell receptor PD-1. Binding of PD-1 to its ligands, PD-L1 and PD-L2, inhibits proliferation of T cells and production of cytokines. This naturally serves to dampen potentially harmful excessive immune responses. Upregulation of PD-1 and/or its ligands can be observed in tumors and people with chronic viral infection, including HIV. This upregulation can inhibit T-cell immune surveillance, which may result in tumor growth or poor control of infection.
Pembrolizumab is an IgG4 kappa monoclonal antibody that binds to PD-1, thus blocking the receptor from binding with its ligands. In cancer indications, inhibition of PD-1 induces an antitumor immune response, which in turn reduces tumor growth. The Food and Drug Administration has approved pembrolizumab for treatment of unresectable or metastatic melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, and other cancers. Similarly, in animal models of HIV and in vitro studies, PD-1 blockade was associated with a decrease in viral load and an increase in CD8+ T cells. A clinical trial to examine the effects of PD-1 inhibition by pembrolizumab on HIV infection is thus supported by the data.
The purpose of this study is to evaluate, in a randomized, double-blind, placebo-controlled study, the safety and tolerability of a single dose of pembrolizumab in HIV-infected participants who have controlled viremia with a low T-cell count (less than or equal to 350 cells/mm^3). Study participants will be followed for 96 weeks after receiving the study drug and will be assessed for adverse events, CD4+ and CD8+ T-cell counts, PD-1 expression, CD8+ T-cell anti-HIV activity, and viral load. If a single dose of pembrolizumab appears to be safe and tolerable, then larger multi-dose and efficacy studies can be planned.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled Study of a Single Dose of Pembrolizumab in HIV-Infected People|
|Estimated Study Start Date :||June 26, 2018|
|Estimated Primary Completion Date :||November 30, 2021|
|Estimated Study Completion Date :||November 30, 2021|
Single dose of 200 mg (IV infusion)
Pembrolizumab, 200 mg, or placebo via intravenous (IV) infusion, single dose.
Placebo Comparator: 2
Single dose (IV infusion)
- The occurrence of Grade 3 or higher AEs. [ Time Frame: 96 weeks after receiving the study drug ]
- Grade 2 or higher autoimmune events requiring corticosteroid therapy. [ Time Frame: 96 weeks after receiving the study drug ]
- Magnitude and duration of decreased expression of PD-1 relative to baseline levels on lymphocytes. [ Time Frame: 96 weeks after receiving the study drug. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03367754
|Contact: Julia B Purdy, C.R.N.P.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Joseph A Kovacs, M.D.||National Institutes of Health Clinical Center (CC)|