Combination Therapy With 3BNC117 and 10-1074 in HIV-Infected Individuals
- Conditions
- HIV
- Interventions
- Biological: PlaceboBiological: 3BNC117 and 10-1074
- Registration Number
- NCT03571204
- Brief Summary
Background:
Human immunodeficiency virus (HIV) affects the immune system. The main function of the immune system is protect you from infections and other diseases such as cancer. HIV attacks and cripples the immune system making people more susceptible to a variety of infections and cancers. Currently, the standard treatment for HIV infection is a daily administration of anti-HIV drugs. These drugs are called combination antiretroviral therapy (ART). ART is very effective at suppressing HIV, but does not cure HIV infection. ART must be taken continuously for life to be effective. ART can stop being effective if not taken correctly and can cause permanent side effects. Researchers want to see if two new products can control HIV infection without the use of ART. The products are the antibodies 3BNC117 and 10-1074.
Objective:
To see if 3BNC117 and 10-1074 are safe and can control HIV levels in the blood of people who are not taking ART or people who stop taking their ART during the study. .
Eligibility:
Adults ages 18-65 with HIV who are:
* on ART and willing to stop treatment for at least 28 weeks
* OR not taking ART with low levels of HIV in the blood
Design:
Participants will be screened with a physical exam, medical history, and blood, heart, and urine tests.
Participants will get the 2 study products or salt water (placebo). A thin tube will be placed in an arm vein. Each product will be given directly into the vein for about 1 hour.
To help collect blood cells to study in the laboratory, participants may have a procedure known as leukapheresis in which blood will be removed through a needle in the arm. Some of the white blood cells will be separated from the blood and used for research studies to see how 3BNC117 and 10-1074 effects HIV and the immune system. The rest of the blood will be returned to the person through another needle in the arm.
Participants will have 18 study visits over 28 weeks. They will repeat some screening tests. They may have leukapheresis again.
At 8 study visits, participants will get the study products or placebo.
All participants will be followed for at least 24 weeks after their last dose of the study infusions. Participants who are in the Group that stops ART will be monitored closely to make sure the levels of virus in their blood do not go to high. If at any time during this the study a person develops HIV-related symptoms, or if the viral levels go up to high levels for more than 4 weeks, ART will be restarted and no further infusions of 3BNC117 and 10-1074 will be given.
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- Detailed Description
Recent advances in antibody cloning technologies have led to the discovery of a number of highly potent and HIV-specific broadly neutralizing monoclonal antibodies (bNAbs) from B cells of HIV-infected individuals. It has been shown that certain bNAbs can prevent acquisition of the virus, suppress viral replication, delay and/or prevent plasma viral rebound following treatment interruption in Simian Immunodeficiency virus (SIV)-infected animals and block cell-to-cell transmission of laboratory-adapted HIV in vitro. In light of these encouraging outcomes, a number of clinical trials have been conducted in recent years in order to explore the feasibility of achieving sustained virologic suppression using a single bNAb in HIV-infected individuals following analytical treatment interruption (ATI). Despite the fact that repeated administration of a single bNAb was safe and well-tolerated, the vast majority of study subjects experienced plasma viral rebound following ATI, clearly demonstrating that successful passive immunotherapy will require different approach, including the use of a combination of 2 or more bNAbs to achieve extended periods of virologic suppression.
Given a major emphasis on current HIV research lies in the possibility of achieving ART-free virologic remission, it is of great interest to investigate whether a combination of potent HIV- specific bNAbs, such as 3BNC117 and 10-1074, can prevent plasma viral rebound in infected individuals upon discontinuation of ART or suppress viral replication in subjects who are not taking ART.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 27
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group 1: ART prior to placebo treatment in HIV-1 subject Placebo Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks. Group 1: ART prior to 3BNC117 + 10-1074 in HIV-1 subject 3BNC117 and 10-1074 Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks. Group 2: 3BNC117 + 10-1074 in HIV-1 subject 3BNC117 and 10-1074 Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.
- Primary Outcome Measures
Name Time Method Participants With Grade 3 or Higher Adverse Events 29 months Participants with grade 3 or higher adverse events (AE), including serious adverse advents. AE severity was graded according to the Division of Aids Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1, July, 2017
- Secondary Outcome Measures
Name Time Method Participants Who Experienced Rebound of Plasma Viremia 28 weeks Difference between the treatment and placebo arms in the number of participants who experienced rebound of plasma viremia and met criteria to restart ART prior to study week 28.
Participants Who Achieved Suppression of Viremia 28 weeks Participants who achieved suppression of viremia to \<40 copies/ml by study week 28
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States