A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117
- Conditions
- HealthyHIV
- Interventions
- Biological: 3 mg/kg, single dose IV administration of 3BNC117Biological: 10 mg/kg, two doses IV of 3BNC117Biological: 1 mg/kg, single dose IV administration of 3BNC117Biological: 30 mg/kg, single dose IV administration of 3BNC117Biological: 30 mg/kg, two doses IV of 3BNC117Biological: 10 mg/kg, single dose IV administration of 3BNC117
- Registration Number
- NCT02018510
- Lead Sponsor
- Rockefeller University
- Brief Summary
The proposed study is a first-in-man phase I study that aims to evaluate the safety, tolerability and pharmacokinetics of 3BNC117 in HIV-infected and HIV-uninfected subjects, and its antiretroviral activity in HIV-infected subjects.
- Detailed Description
In preclinical studies carried out in humanized mice and non-human primates, 3BNC117 alone or in combination with other neutralizing antibodies led to protection from HIV-1 or SHIV infection and also to sustained suppression of HIV-1 plasma viremia. The aims of this protocol are to evaluate the safety, tolerability and pharmacokinetics profile of 3BNC117 in both HIV-infected and HIV-uninfected subjects,and its antiretroviral activity in HIV-infected subjects.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
-
Group 1 (HIV-uninfected):
- Adult males and females, age 18 to 65
- Amenable to HIV risk reduction counseling and agrees to maintaining behavior consistent with low risk of HIV exposure;
- If a sexually active male or female, participating in sexual activity that could lead to pregnancy, agrees to use an effective method of contraception throughout the study.
-
Groups 2-5 (HIV-infected):
- Age 18 to 65
- HIV infection confirmed by ELISA and immunoblot
- Groups 2A-D - on ART with HIV-1 plasma RNA levels below 100,000 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA level between 2,000-100,000 copies/ml by standard assays on 2 occasions at least 1 week apart;
- Group 2E - Untreated HIV-infected (not on ART for at least 8 weeks): HIV-1 RNA plasma levels between 2,000 - 100,000 copies/ml;
- Group 3 - Untreated HIV controllers (not on ART for at least 8 weeks): HIV-1 RNA plasma level of < 2,000 copies/ml by standard assays, on 2 occasions, at least 1 week apart, and ART-naive.
- Group 4 - ART treated with HIV-1 RNA plasma level of > 20 copies/ml by standard assays on 2 occasions, at least 1 week apart, while on combination antiretroviral therapy;
- Groups 5A and 5B - ART treated with HIV-1 RNA plasma level of < 20 copies/ml by standard assays on 2 occasions, at least 1 week apart, while on combination antiretroviral therapy;
- Current CD4 cell count > 300 cells/µl
- If sexually active male and female, participating in sexual activity that could lead to pregnancy, agrees to use an effective method of contraception throughout the study.
Exclusion criteria:
-
Group 1 (HIV-uninfected):
-
Confirmed HIV-1 or HIV-2 infection;
-
History of immunodeficiency or autoimmune disease; use 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 that in the opinion of the investigator would preclude participation;
-
Within the 12 months prior to enrollment, the volunteer has a history of sexually transmitted disease;
-
Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);
-
Laboratory abnormalities in the parameters listed below:
- Absolute neutrophil count ≤ 2,000
- Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male
- Platelet count ≤ 140,000
- ALT ≥ 1.25 x ULN
- AST ≥ 1.25 x ULN
- Total bilirubin ≥ 1.1 ULN
- Creatinine ≥ 1.1 x ULN
- Coagulation parameters (PT, PTT, INR) ≥ 1.1 x ULN
-
Pregnancy or breastfeeding;
-
Any vaccination within 14 days prior to 3BNC117 administration;
-
Receipt of any experimental HIV vaccine in the past or monoclonal antibody therapy of any kind in the past;
-
Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
-
-
Groups 2-5 (HIV-infected):
-
History of AIDS-defining illness
-
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, other than HIV infection, that in the opinion of the investigator would preclude participation;
-
Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);
-
Laboratory abnormalities in the parameters listed below:
- Absolute neutrophil count ≤ 1,300
- Hemoglobin ≤ 10 gm/dL
- Platelet count ≤ 125,000
- ALT ≥ 2.0 x ULN
- AST ≥ 2.0 x ULN
- Total bilirubin ≥ 1.1 ULN
- Creatinine ≥ 1.1 x ULN
- Coagulation parameters ≥ 1.1 x ULN;
-
Current antiretroviral regimen includes either maraviroc or enfuvirtide;
-
Pregnancy or breastfeeding;
-
Any vaccination within 14 days prior to 3BNC117 administration;
-
Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past;
-
Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
-
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Groups 1B 3 mg/kg, single dose IV administration of 3BNC117 HIV-uninfected individuals 3 mg/kg, single dose IV administration of 3BNC117 Group 1D 10 mg/kg, two doses IV of 3BNC117 HIV-uninfected individuals 10 mg/kg, two doses IV of 3BNC117 Group 1A 1 mg/kg, single dose IV administration of 3BNC117 HIV-uninfected individuals 1 mg/kg, single dose IV administration of 3BNC117 Group 1E 30 mg/kg, single dose IV administration of 3BNC117 HIV-uninfected individuals 30 mg/kg, single dose IV administration of 3BNC117 Group 1F 30 mg/kg, two doses IV of 3BNC117 HIV-uninfected individuals 30 mg/kg, two doses IV of 3BNC117 Group 2C 10 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals on or off ART 10 mg/kg, single dose IV administration of 3BNC117 Group 2D 30 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals on or off ART 30 mg/kg, single dose IV administration of 3BNC117 Group 2E 30 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals off ART, VL 2,000-100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117 Group 3 30 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals off ART, VL \< 2,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117 Group 5B 30 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals on ART, VL \< 20 copies/ml 30 mg/kg, single dose IV administration of 3BNC117 Group 1C 10 mg/kg, single dose IV administration of 3BNC117 HIV-uninfected individuals 10 mg/kg, single dose IV administration of 3BNC117 Group 5A 10 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals on ART, VL \< 20 copies/ml 10 mg/kg, single dose IV administration of 3BNC117 Group 4 30 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals on ART, VL \< 100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117 Group 2A 1 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals on or off ART 1 mg/kg, single dose IV administration of 3BNC117 Group 2B 3 mg/kg, single dose IV administration of 3BNC117 HIV-infected individuals on or off ART 3 mg/kg, single dose IV administration of 3BNC117
- Primary Outcome Measures
Name Time Method Safety and tolerability 24 weeks To evaluate the safety and tolerability profile of one or two intravenous infusions of 3BNC117 at 3 increasing dose levels in HIV-infected and HIV-uninfected individuals.
- Secondary Outcome Measures
Name Time Method Pharmacokinetic profile 24 hours post infusion To determine the pharmacokinetic profile of one or two intravenous infusions of 3BNC117 in HIV-uninfected and HIV-infected subjects.
Trial Locations
- Locations (4)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Cologne
🇩🇪Cologne, Germany
The Rockefeller University
🇺🇸New York, New York, United States
Weill Cornell Medical Center
🇺🇸New York, New York, United States