Ignite Creation Date:
2024-05-06 @ 10:51 AM
Last Modification Date:
2024-10-26 @ 12:36 PM
Study NCT ID:
NCT03367754
Status:
RECRUITING
Last Update Posted:
2024-05-30
First Post:
2017-12-08
Brief Title:
A Single Dose of Pembrolizumab in HIV-Infected People
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Double-Blind Placebo-Controlled Study of a Single Dose of Pembrolizumab in HIV-Infected Patients
Status:
RECRUITING
Status Verified Date:
2024-05-28
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 cellsmm3
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
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 cellsmm3
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
Detailed Description:
A subset of HIV-infected patients those with poor immunologic response to combined antiretroviral therapy CD4 T-cell count of less than 300-350 cellsmm3 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 andor 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 100 cellsmm3 and less than or equal to 350 cellsmm3 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
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 andor 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 100 cellsmm3 and less than or equal to 350 cellsmm3 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 18-CC-0013 | None | None | None |