Ignite Creation Date:
2024-05-06 @ 6:17 PM
Last Modification Date:
2024-10-26 @ 2:45 PM
Study NCT ID:
NCT05612178
Status:
RECRUITING
Last Update Posted:
2024-06-25
First Post:
2022-11-09
Brief Title:
A Study to Evaluate the Safety and Effects of Repeated Doses of 3BNC117-LS and 10-1074-LS on Persistent Viral Reservoirs in People Living With HIV and on Suppressive Antiretroviral Therapy
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Placebo-controlled Study to Evaluate the Safety and Effects of Repeated Doses of 3BNC117-LS and 10-1074-LS on Persistent Viral Reservoirs in People Living With HIV and on Suppressive Antiretroviral Therapy
Status:
RECRUITING
Status Verified Date:
2024-10-22
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
Antiretroviral therapy ART can suppress HIV to undetectable levels in people but the virus rebounds quickly if the drug treatment is stopped this is because HIV can remain dormant in a pool of blood cells called the persistent viral reservoir PVR Yet lifelong ART is expensive and can lead to serious side effects over the long term Some drugs may be more effective at reducing the PVR
Objective
To see if 2 study drugs 3BNC117-LS and 10-1074-LS are safe and if they can lower the number of HIV-infected blood cells in people with HIV who are on ART
Eligibility
People aged 18 to 70 years with HIV who are on ART
Design
Participants will be screened They will have a physical exam and blood and urine tests They will undergo leukapheresis Leukapheresis is a procedure where blood is drawn from a needle in one arm The blood will pass through a machine that separates out the white blood cells The remaining blood will be given back through a second needle in the other arm
The study drugs or placebo normal saline will be administered 3 times at 20-week intervals The drugs will be given through a tube attached to a needle inserted into a vein in the arm This will take 1 hour Some participants will receive only a saline solution They will not know if they are getting the drugs or the placebo
Participants will undergo leukapheresis up to 4 more times during the study
Participants will have follow-up visits every 10 weeks until the study ends
Antiretroviral therapy ART can suppress HIV to undetectable levels in people but the virus rebounds quickly if the drug treatment is stopped this is because HIV can remain dormant in a pool of blood cells called the persistent viral reservoir PVR Yet lifelong ART is expensive and can lead to serious side effects over the long term Some drugs may be more effective at reducing the PVR
Objective
To see if 2 study drugs 3BNC117-LS and 10-1074-LS are safe and if they can lower the number of HIV-infected blood cells in people with HIV who are on ART
Eligibility
People aged 18 to 70 years with HIV who are on ART
Design
Participants will be screened They will have a physical exam and blood and urine tests They will undergo leukapheresis Leukapheresis is a procedure where blood is drawn from a needle in one arm The blood will pass through a machine that separates out the white blood cells The remaining blood will be given back through a second needle in the other arm
The study drugs or placebo normal saline will be administered 3 times at 20-week intervals The drugs will be given through a tube attached to a needle inserted into a vein in the arm This will take 1 hour Some participants will receive only a saline solution They will not know if they are getting the drugs or the placebo
Participants will undergo leukapheresis up to 4 more times during the study
Participants will have follow-up visits every 10 weeks until the study ends
Detailed Description:
Study Description
This is randomized placebo-controlled study of the safety and virologic activity of the 3BNC117-LS plus 10-1074-LS broadly neutralizing antibody bNAb combination during standard antiretroviral therapy ART
Participants will be enrolled sequentially and randomized to receive 3BNC117-LS plus 10-1074-LS or placebo sterile saline at a 11 ratio Participants will receive two intravenous infusions of 3BNC117-LS dosed at 30 mgkg and 10-1074-LS dosed at 10 mgkg or placebo at weeks 0 and 20 Participants will remain on ART during the study
Objectives
Primary Objectives
-To evaluate the safety and tolerability of repeated doses of 3BNC117-LS and 10-1074-LS in adults living with human immunodeficiency virus HIV during suppressive ART
Secondary Objectives
To evaluate the impact of 3BNC117-LS and 10-1074-LS on intact human immunodeficiency type 1 HIV-1 proviruses over time in adults living with HIV during suppressive ART
To determine the effects of repeated doses of 3BNC117-LS and 10- 1074-LS during suppressive ART on HIV-1 specific cellular immune responses by enzyme-linked immunosorbent spot ELISpot
To describe the pharmacokinetic parameters of the repeated doses of 3BNC117-LS and 10-1074-LS in adults living with HIV during suppressive ART
Exploratory Objectives
To characterize the HIV-1 reservoir in peripheral blood during and following repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
To evaluate effects on HIV-1 transcriptional activity during and following repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
To characterize host HIV-1 specific humoral cellular and innate immune responses during and following repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
To correlate HIV-1 specific immune responses and effects on intact proviruses
To correlate virologic outcomes with bNAb sensitivity of reservoir proviruses
EndpointsTAB
Primary Endpoints
-The occurrence of solicited and unsolicited grade 3 or higher adverse events AE including confirmed laboratory abnormalities that are possibly probably or definitely related to 3BNC117-LS andor 10- 1074-LS or premature study treatment discontinuation due to an AE regardless of grade
Secondary Endpoints
The occurrence of serious adverse events regardless of relationship to 3BNC117-LS andor 10-1074-LS
Change in the intact proviral reservoir size measured by quadruplex polymerase chain reaction Q4PCR andor intact proviral deoxyribonucleic acid assay IPDA from baseline to weeks 40 and
80 after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Changes in HIV-1 specific T cell immune responses in peripheral blood measured by ELISpot before during and after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Pharmacokinetic parameters including peak concentrations half- life area under curve and clearance rate of repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
Exploratory Endpoints
Size of the latent HIV-1 reservoir measured by quantitative viral outgrowth assay QVOA andor other appropriate assays before during and after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Composition of the intact proviral reservoir before and after immunotherapy with 3BNC117-LS and 10-1074-LS during suppressive ART by Q4PCR or other appropriate assays that may become available
The half-life of the HIV-1 intact proviral reservoir during 3BNC117- LS and 10-1074-LS therapy and ART suppression
HIV-1 transcriptional activity as determined by spliced and unspliced HIV-1 ribonucleic acid RNA in circulating total CD4 T cells andor other appropriate assays before during and after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Changes in HIV-1 specific T cell immune responses in peripheral blood measured by assays such as polyfunctional intracellular cytokine staining ICS and viral inhibition assay before during and after immunotherapy with 3BNC117-LS and 10-1074-LS during suppressive ART
Changes in antibody dependent cell-mediated cytotoxicity ADCC against HIV-1-infected CD4 T-cells by ex vivo autologous natural killer cells before and after immunotherapy with 3BNC117-LS and 10-1074-LS during suppressive ART
Correlation between magnitude breadth and functionality of HIV-1 specific T cell immune responses and effects on intact proviruses
Correlation between changes in intact proviruses and bNAb sensitivity of reservoir proviruses determined by Env sequencing
Correlation between HIV-1 transcriptional activity and changes in the composition of the intact proviral reservoir
This is randomized placebo-controlled study of the safety and virologic activity of the 3BNC117-LS plus 10-1074-LS broadly neutralizing antibody bNAb combination during standard antiretroviral therapy ART
Participants will be enrolled sequentially and randomized to receive 3BNC117-LS plus 10-1074-LS or placebo sterile saline at a 11 ratio Participants will receive two intravenous infusions of 3BNC117-LS dosed at 30 mgkg and 10-1074-LS dosed at 10 mgkg or placebo at weeks 0 and 20 Participants will remain on ART during the study
Objectives
Primary Objectives
-To evaluate the safety and tolerability of repeated doses of 3BNC117-LS and 10-1074-LS in adults living with human immunodeficiency virus HIV during suppressive ART
Secondary Objectives
To evaluate the impact of 3BNC117-LS and 10-1074-LS on intact human immunodeficiency type 1 HIV-1 proviruses over time in adults living with HIV during suppressive ART
To determine the effects of repeated doses of 3BNC117-LS and 10- 1074-LS during suppressive ART on HIV-1 specific cellular immune responses by enzyme-linked immunosorbent spot ELISpot
To describe the pharmacokinetic parameters of the repeated doses of 3BNC117-LS and 10-1074-LS in adults living with HIV during suppressive ART
Exploratory Objectives
To characterize the HIV-1 reservoir in peripheral blood during and following repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
To evaluate effects on HIV-1 transcriptional activity during and following repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
To characterize host HIV-1 specific humoral cellular and innate immune responses during and following repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
To correlate HIV-1 specific immune responses and effects on intact proviruses
To correlate virologic outcomes with bNAb sensitivity of reservoir proviruses
EndpointsTAB
Primary Endpoints
-The occurrence of solicited and unsolicited grade 3 or higher adverse events AE including confirmed laboratory abnormalities that are possibly probably or definitely related to 3BNC117-LS andor 10- 1074-LS or premature study treatment discontinuation due to an AE regardless of grade
Secondary Endpoints
The occurrence of serious adverse events regardless of relationship to 3BNC117-LS andor 10-1074-LS
Change in the intact proviral reservoir size measured by quadruplex polymerase chain reaction Q4PCR andor intact proviral deoxyribonucleic acid assay IPDA from baseline to weeks 40 and
80 after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Changes in HIV-1 specific T cell immune responses in peripheral blood measured by ELISpot before during and after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Pharmacokinetic parameters including peak concentrations half- life area under curve and clearance rate of repeated doses of 3BNC117-LS and 10-1074-LS during suppressive ART
Exploratory Endpoints
Size of the latent HIV-1 reservoir measured by quantitative viral outgrowth assay QVOA andor other appropriate assays before during and after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Composition of the intact proviral reservoir before and after immunotherapy with 3BNC117-LS and 10-1074-LS during suppressive ART by Q4PCR or other appropriate assays that may become available
The half-life of the HIV-1 intact proviral reservoir during 3BNC117- LS and 10-1074-LS therapy and ART suppression
HIV-1 transcriptional activity as determined by spliced and unspliced HIV-1 ribonucleic acid RNA in circulating total CD4 T cells andor other appropriate assays before during and after dosing with 3BNC117-LS and 10-1074-LS during suppressive ART
Changes in HIV-1 specific T cell immune responses in peripheral blood measured by assays such as polyfunctional intracellular cytokine staining ICS and viral inhibition assay before during and after immunotherapy with 3BNC117-LS and 10-1074-LS during suppressive ART
Changes in antibody dependent cell-mediated cytotoxicity ADCC against HIV-1-infected CD4 T-cells by ex vivo autologous natural killer cells before and after immunotherapy with 3BNC117-LS and 10-1074-LS during suppressive ART
Correlation between magnitude breadth and functionality of HIV-1 specific T cell immune responses and effects on intact proviruses
Correlation between changes in intact proviruses and bNAb sensitivity of reservoir proviruses determined by Env sequencing
Correlation between HIV-1 transcriptional activity and changes in the composition of the intact proviral reservoir
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 |
|---|---|---|---|
| 001037-I | None | None | None |