Healthy, HIV
Conditions
Keywords
Healthy Volunteers, HIV
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.
Interventions
BIOLOGICAL1 mg/kg, single dose IV administration of 3BNC117
1 mg/kg, single dose IV administration of 3BNC117
BIOLOGICAL3 mg/kg, single dose IV administration of 3BNC117
3 mg/kg, single dose IV administration of 3BNC117
BIOLOGICAL10 mg/kg, single dose IV administration of 3BNC117
10 mg/kg, single dose IV administration of 3BNC117
BIOLOGICAL30 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
BIOLOGICAL10 mg/kg, two doses IV of 3BNC117
10 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
BIOLOGICAL30 mg/kg, two doses IV of 3BNC117
30 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
Sponsors
Weill Medical College of Cornell University
Brigham and Women's Hospital
University of Cologne
Rockefeller University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Germany, United States
Outcome results
None listed