Ignite Creation Date:
2024-05-06 @ 10:21 AM
Last Modification Date:
2024-10-26 @ 12:29 PM
Study NCT ID:
NCT03239899
Status:
COMPLETED
Last Update Posted:
2024-02-13
First Post:
2017-08-03
Brief Title:
PD-1 Inhibition to Determine CNS Reservoir of HIV-Infection
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
PD-1 Inhibition to Determine CNS Reservoir of HIV-Infection
Status:
COMPLETED
Status Verified Date:
2023-02-13
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
HIV affects millions of people The disease may hide in the brain even in people with well-controlled HIV without cancer Then it may wake up and continue The drug pembrolizumab uses the bodys immune system to fight cells like cancer cells It is approved to treat some cancers but not HIV Researchers want to see if it is safe for HIV-positive people without cancer This study is not for HIV treatment only one dose of the drug will be used
Objective
To learn if the drug pembrolizumab used to treat certain cancers is safe for HIV-positive people
Eligibility
Adults ages 18 and older with HIV who are in another NIH protocol
Design
Participants will be screened with
Medical history
Physical and neurological exams
Blood tests
Lumbar puncture The lower back will be numbed A needle will remove fluid from between back bones
FDG-PETCT A radioactive sugar will be injected in a thin plastic tube catheter inserted in an arm vein Participants will rest for an hour urinate then lie in the scanner A mask will hold the head still
Leukapheresis An optional procedure at baseline White blood cells are removed from you using a serum cell separator machine
Women who can become pregnant cannot take pembrolizumab Men who take it must use 2 kinds of contraception
Participants will have up to 7 more visits which repeat some screening tests
At 1 visit participants will get one dose of pembrolizumab by catheter for 30 minutes They will get allergy and pain medicines
At 2 visits participants will have a brain MRI They will get a contrast agent by catheter They will lie in a metal cylinder that takes pictures for 1-2 hours They will get earplugs for loud sounds
HIV affects millions of people The disease may hide in the brain even in people with well-controlled HIV without cancer Then it may wake up and continue The drug pembrolizumab uses the bodys immune system to fight cells like cancer cells It is approved to treat some cancers but not HIV Researchers want to see if it is safe for HIV-positive people without cancer This study is not for HIV treatment only one dose of the drug will be used
Objective
To learn if the drug pembrolizumab used to treat certain cancers is safe for HIV-positive people
Eligibility
Adults ages 18 and older with HIV who are in another NIH protocol
Design
Participants will be screened with
Medical history
Physical and neurological exams
Blood tests
Lumbar puncture The lower back will be numbed A needle will remove fluid from between back bones
FDG-PETCT A radioactive sugar will be injected in a thin plastic tube catheter inserted in an arm vein Participants will rest for an hour urinate then lie in the scanner A mask will hold the head still
Leukapheresis An optional procedure at baseline White blood cells are removed from you using a serum cell separator machine
Women who can become pregnant cannot take pembrolizumab Men who take it must use 2 kinds of contraception
Participants will have up to 7 more visits which repeat some screening tests
At 1 visit participants will get one dose of pembrolizumab by catheter for 30 minutes They will get allergy and pain medicines
At 2 visits participants will have a brain MRI They will get a contrast agent by catheter They will lie in a metal cylinder that takes pictures for 1-2 hours They will get earplugs for loud sounds
Detailed Description:
Objective
In this Phase I proof-of-concept study we aim to determine the safety and tolerability of pembrolizumab an FDA-approved monoclonal antibody against programmed cell death protein PD-1 in viremically suppressed human immunodeficiency virus-1 HIV positive patients We are examining the correlation of immune activation and suppression markers in viremically suppressed HIV positive patients with the effects of pembrolizumab on immune restoration function eg CD4 count HIV viral load and immune activation eg HIV-specific T-cell responses
Study Population
HIV is estimated to infect 376 million people globally with 690000 deaths and 15 million new infections occurring yearly There is no cure Opportunistic infections and neoplasms contribute to a large portion of mortality and morbidity within the HIV-positive population Even in well- controlled viremically suppressed patients neurologic complications including HIV-associated neurocognitive disorder continue to contribute to disease morbidity and mortality
There is evidence that HIV reservoirs contribute to the inability to cure HIV infection In the brain macrophages and astrocytes harbor HIV It is theorized that the brain is a potential reservoir for replication competent HIV PD-1 expression is elevated in patients with HIV compared to uninfected controls Upregulated PD-1 expression is associated with higher viral load and increased mortality in infections1 PD-1 co-expression on regulatory T-cells has been shown to correlate with disease progression in perinatally-infected HIV-positive children Drugs targeting the PD-1 pathway in HIV infection have shown upregulation of T-cell responses that are potentially critical to eradication of infection Pembrolizumab is an attractive option due to its mechanism of action although it has been rarely used in the HIV population
Design
In this single-center single-arm open label baseline-versus-treatment phase I clinical trial twelve patients with HIV-1 infection receive a one-time dose of 200mg pembrolizumab with a baseline study period of 3 weeks a one-day treatment phase and a 6-month post treatment phase Outcome measures are collected every 3 to 6 weeks for the duration of the study
Outcome Measures
The primary outcome is the safety and tolerability of pembrolizumab which is measured by clinical exam laboratory studies and adverse event tabulations using the Common Terminology Criteria for Adverse Events CTCAE v50
In addition viral and immunologic outcome measures investigating the impact of pembrolizumab on HIV-1 biology and its effects on immune function is measured in the CSF and periphery including single copy HIV analysis CD4 T-cell count PD-1 lymphocyte expression and T-cell phenotype analysis T-cell proliferation against HIV-proteins CSF cytokine analysis andor CSF antibody profiling LIPS These additional studies offer indirect proof of a HIV viral reservoir in the CNS as well as potential efficacy of pembrolizumab in reversing immune exhaustion against latent HIV
In this Phase I proof-of-concept study we aim to determine the safety and tolerability of pembrolizumab an FDA-approved monoclonal antibody against programmed cell death protein PD-1 in viremically suppressed human immunodeficiency virus-1 HIV positive patients We are examining the correlation of immune activation and suppression markers in viremically suppressed HIV positive patients with the effects of pembrolizumab on immune restoration function eg CD4 count HIV viral load and immune activation eg HIV-specific T-cell responses
Study Population
HIV is estimated to infect 376 million people globally with 690000 deaths and 15 million new infections occurring yearly There is no cure Opportunistic infections and neoplasms contribute to a large portion of mortality and morbidity within the HIV-positive population Even in well- controlled viremically suppressed patients neurologic complications including HIV-associated neurocognitive disorder continue to contribute to disease morbidity and mortality
There is evidence that HIV reservoirs contribute to the inability to cure HIV infection In the brain macrophages and astrocytes harbor HIV It is theorized that the brain is a potential reservoir for replication competent HIV PD-1 expression is elevated in patients with HIV compared to uninfected controls Upregulated PD-1 expression is associated with higher viral load and increased mortality in infections1 PD-1 co-expression on regulatory T-cells has been shown to correlate with disease progression in perinatally-infected HIV-positive children Drugs targeting the PD-1 pathway in HIV infection have shown upregulation of T-cell responses that are potentially critical to eradication of infection Pembrolizumab is an attractive option due to its mechanism of action although it has been rarely used in the HIV population
Design
In this single-center single-arm open label baseline-versus-treatment phase I clinical trial twelve patients with HIV-1 infection receive a one-time dose of 200mg pembrolizumab with a baseline study period of 3 weeks a one-day treatment phase and a 6-month post treatment phase Outcome measures are collected every 3 to 6 weeks for the duration of the study
Outcome Measures
The primary outcome is the safety and tolerability of pembrolizumab which is measured by clinical exam laboratory studies and adverse event tabulations using the Common Terminology Criteria for Adverse Events CTCAE v50
In addition viral and immunologic outcome measures investigating the impact of pembrolizumab on HIV-1 biology and its effects on immune function is measured in the CSF and periphery including single copy HIV analysis CD4 T-cell count PD-1 lymphocyte expression and T-cell phenotype analysis T-cell proliferation against HIV-proteins CSF cytokine analysis andor CSF antibody profiling LIPS These additional studies offer indirect proof of a HIV viral reservoir in the CNS as well as potential efficacy of pembrolizumab in reversing immune exhaustion against latent HIV
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 |
|---|---|---|---|
| 17-N-0145 | None | None | None |