a phase 1, open label, dose-escalation study of the safety, pharmacokinetics and antiretroviral activity of 3bnc117

Conditions: Healthy; HIV

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.

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.

Eligibility criteria:
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.

Keywords: healthy volunteers hiv