3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals
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|ClinicalTrials.gov Identifier: NCT04250636|
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : August 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Human Immunodeficiency Virus||Drug: 3BNC117-LS Drug: 10-1074-LS||Phase 1|
The proposed study is a phase 1, open label, single arm study to evaluate the safety, pharmacokinetics and antiviral activity of single intravenous infusions of 3BNC117-LS and 10-1074-LS in viremic HIV-infected individuals.
Ten eligible participants will be enrolled sequentially in the study and will receive each mAb, dosed at 30 mg/kg intravenously and in sequence on study day 0. Following mAb administration, study participants will return for safety assessments on days 1 and 3, and weeks 1, 2, 3 and 4 following dosing, then bi-weekly or monthly until the end of study follow up. All participants will be followed for 24 weeks after 3BNC117-LS and 10-1074-LS administration.
Safety assessments will be performed at multiple time points following 3BNC117-LS and 10-1074-LS infusions. Serum samples for pharmacokinetic (PK) measurements will be collected before and at the end each mAb infusion administration and at multiple subsequent time points during study follow up. Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS and 10-1074-LS infusions (screen and day 0) and at every follow up visit. T cell subsets will also be monitored during study follow up. Assessments will also include measurement of anti-drug antibody responses and sequencing of plasma envelope before infusions and after viral rebound (first time point after viremia nadir is reached and viral load (VL) is > 1,000 copies/ml).
Participants will be advised and encouraged to start antiretroviral therapy (ART) within 4 weeks of receiving 3BNC117-LS and 10-1074-LS infusions or sooner if: VL fails to decrease by > 0.5 log10 copies/ml within 2 weeks of antibody infusions, VL increases > 0.5 log10 copies/ml between weekly measurements or significant T-cell decline (confirmed CD4+ T cells < 200 cells/μl) is noted.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label, Single Arm Study of the Safety, Pharmacokinetics and Antiretroviral Activity of the Combination of 3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals.|
|Actual Study Start Date :||August 6, 2020|
|Estimated Primary Completion Date :||February 28, 2022|
|Estimated Study Completion Date :||February 28, 2022|
Experimental: Study Participants
HIV-infected individuals, off ART, and with plasma HIV-1 RNA levels between 500 and 100,000 copies/ml by standard assays. Study participants will receive a single intravenous infusion of 3BNC117-LS and a single infusion of 10-1074-LS. The antibodies will be administered sequentially and dosed at 30 mg/kg.
Intravenous infusion of 3BNC117-LS at 30mg/kg
Other Name: Monoclonal Antibody
Intravenous infusion of 10-1074-LS at 30mg/kg
Other Name: Monoclonal Antibody
- Grade 3 and serious adverse events [ Time Frame: 24 weeks ]The number of participants with treatment-related solicited and unsolicited grade 3 and serious adverse events (including confirmed laboratory abnormalities).
- Peak concentration [ Time Frame: 24 weeks ]Peak concentration of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
- Half-life [ Time Frame: 24 weeks ]Half-life of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
- Area under curve [ Time Frame: 24 weeks ]Area under curve of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
- Clearance Rate [ Time Frame: 24 weeks ]Clearance rate of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
- The decline in plasma HIV-1 RNA level [ Time Frame: 4 weeks ]- The decline in plasma HIV-1 RNA level after 3BNC117-LS plus 10-1074-LS intravenous infusions in viremic HIV-infected individuals through week 4 after infusions.
- Anti-drug Antibodies [ Time Frame: 24 weeks ]Proportion of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response.
- Adverse Events [ Time Frame: 24 weeks ]The number of adverse events that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.
- Laboratory Abnormalities [ Time Frame: 24 weeks ]The number of confirmed laboratory abnormalities that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.
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): NCT04250636
|Contact: Recruitment Specialistfirstname.lastname@example.org|
|United States, New York|
|Weill Cornell Medical Center Clinical Trials Unit||Not yet recruiting|
|New York, New York, United States, 10021|
|Contact: Timothy Wilkin, MD 212-746-4177 email@example.com|
|The Rockefeller University||Recruiting|
|New York, New York, United States, 10065|
|Contact: Recruitment Specialist, MD 800-782-2737 firstname.lastname@example.org|
|Principal Investigator: Marina Caskey, MD|
|United States, Pennsylvania|
|Perelman School of Medicine University of Pennsylvania||Not yet recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Pablo Tebas, MD 215-349-8091 email@example.com|
|Principal Investigator:||Marina Caskey||The Rockefeller University|