Back to results3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals
Primary Purpose
Human Immunodeficiency Virus
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
3BNC117-LS
10-1074-LS
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus focused on measuring 3BNC117-LS, 10-1074-LS, Broadly Neutralizing Antibody
Eligibility Criteria
Inclusion Criteria:
- Males and females, >18 years of age.
- Confirmed HIV-1 infection.
- Off ART for at least 4 weeks with a HIV-1 plasma RNA level between 500 and 100,000 copies/mL (ART-naïve or off ART due to intolerance or by choice).
- Current CD4+ T cell count > 300 cells/μl.
- If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and six months after 3BNC117-LS and 10-1074-LS administration.
Exclusion Criteria:
- Have a history of AIDS-defining illness within 3 years prior to enrollment.
- History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
- Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
- Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
Laboratory abnormalities in the parameters listed below:
- Absolute neutrophil count ≤ 1,000 cells/μl;
- Hemoglobin ≤ 10 gm/dL;
- Platelet count ≤ 100,000 cells/μl;
- ALT ≥ 1.5 x ULN;
- AST ≥ 1.5 x ULN;
- Alkaline phosphatase ≥ 1.5 x ULN;
- Total bilirubin > 1.25 x ULN;
- eGFR < 60 mL/min/1.73m2.
- Pregnancy or lactation.
- Any vaccination within 14 days prior to mAb infusions, except for influenza vaccine.
- Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.
- Receipt of any experimental HIV vaccine or anti-HIV monoclonal antibody therapy in the past.
- History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
- Individuals with known hypersensitivity to any constituent of the investigational products.
Sites / Locations
- Weill Cornell Medical Center Clinical Trials Unit-CLOSED SITE
- The Rockefeller University
- Perelman School of Medicine University of Pennsylvania
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study Participants
Arm Description
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.
Outcomes
Primary Outcome Measures
Grade 3 and Serious Adverse Events
The number of participants with treatment-related solicited and unsolicited grade 3 and serious adverse events (including confirmed laboratory abnormalities).
Peak Concentration
Peak concentration of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
Half-life
Half-life of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
Area Under Curve
Area under curve of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
Maximum Decline in Plasma HIV-1 RNA Level
Maximum 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.
Secondary Outcome Measures
Anti-drug Antibodies
Number of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response.
Adverse Events
The number of adverse events that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.
Laboratory Abnormalities
The number of confirmed laboratory abnormalities that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.
Full Information
NCT ID
NCT04250636
First Posted
January 30, 2020
Last Updated
June 1, 2023
Sponsor
Rockefeller University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Weill Medical College of Cornell University, University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT04250636
Brief Title
3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals
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.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 13, 2020 (Actual)
Primary Completion Date
January 21, 2022 (Actual)
Study Completion Date
February 11, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rockefeller University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Weill Medical College of Cornell University, University of Pennsylvania
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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, each monoclonal antibody (mAb) dosed at 30 mg/kg in viremic human immunodeficiency virus (HIV)-infected individuals.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus
Keywords
3BNC117-LS, 10-1074-LS, Broadly Neutralizing Antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study Participants
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
3BNC117-LS
Other Intervention Name(s)
Monoclonal Antibody
Intervention Description
Intravenous infusion of 3BNC117-LS at 30mg/kg
Intervention Type
Drug
Intervention Name(s)
10-1074-LS
Other Intervention Name(s)
Monoclonal Antibody
Intervention Description
Intravenous infusion of 10-1074-LS at 30mg/kg
Primary Outcome Measure Information:
Title
Grade 3 and Serious Adverse Events
Description
The number of participants with treatment-related solicited and unsolicited grade 3 and serious adverse events (including confirmed laboratory abnormalities).
Time Frame
24 weeks
Title
Peak Concentration
Description
Peak concentration of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
Time Frame
24 weeks
Title
Half-life
Description
Half-life of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
Time Frame
24 weeks
Title
Area Under Curve
Description
Area under curve of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.
Time Frame
24 weeks
Title
Maximum Decline in Plasma HIV-1 RNA Level
Description
Maximum 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.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Anti-drug Antibodies
Description
Number of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response.
Time Frame
24 weeks
Title
Adverse Events
Description
The number of adverse events that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.
Time Frame
24 weeks
Title
Laboratory Abnormalities
Description
The number of confirmed laboratory abnormalities that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females, >18 years of age.
Confirmed HIV-1 infection.
Off ART for at least 4 weeks with a HIV-1 plasma RNA level between 500 and 100,000 copies/mL (ART-naïve or off ART due to intolerance or by choice).
Current CD4+ T cell count > 300 cells/μl.
If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and six months after 3BNC117-LS and 10-1074-LS administration.
Exclusion Criteria:
Have a history of AIDS-defining illness within 3 years prior to enrollment.
History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
Laboratory abnormalities in the parameters listed below:
Absolute neutrophil count ≤ 1,000 cells/μl;
Hemoglobin ≤ 10 gm/dL;
Platelet count ≤ 100,000 cells/μl;
ALT ≥ 1.5 x ULN;
AST ≥ 1.5 x ULN;
Alkaline phosphatase ≥ 1.5 x ULN;
Total bilirubin > 1.25 x ULN;
eGFR < 60 mL/min/1.73m2.
Pregnancy or lactation.
Any vaccination within 14 days prior to mAb infusions, except for influenza vaccine.
Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.
Receipt of any experimental HIV vaccine or anti-HIV monoclonal antibody therapy in the past.
History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
Individuals with known hypersensitivity to any constituent of the investigational products.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marina Caskey
Organizational Affiliation
The Rockefeller University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medical Center Clinical Trials Unit-CLOSED SITE
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
The Rockefeller University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Perelman School of Medicine University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals
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