Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117 Monoclonal Antibody in HIV-infected and HIV-uninfected Volunteers

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Rockefeller University
Sponsor:
Information provided by (Responsible Party):
Rockefeller University
ClinicalTrials.gov Identifier:
NCT02018510
First received: December 17, 2013
Last updated: February 26, 2014
Last verified: February 2014

December 17, 2013
February 26, 2014
January 2014
January 2016   (final data collection date for primary outcome measure)
Safety and tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
To evaluate the safety and tolerability profile of a single intravenous infusion of 3BNC117 at 3 increasing dose levels in HIV-infected and HIV-uninfected individuals.
Same as current
Complete list of historical versions of study NCT02018510 on ClinicalTrials.gov Archive Site
Pharmacokinetic profile [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: No ]
To determine the pharmacokinetic profile of a single intravenous administration of 3BNC117 in HIV-uninfected and HIV-infected subjects.
Same as current
Not Provided
Not Provided
 
A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117 Monoclonal Antibody in HIV-infected and HIV-uninfected Volunteers
A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117 Monoclonal Antibody in HIV-infected and HIV-uninfected Volunteers

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Healthy
  • HIV
  • Biological: 1 mg/kg, single dose IV administration of 3BNC117
    1 mg/kg, single dose IV administration of 3BNC117
  • Biological: 3 mg/kg, single dose IV administration of 3BNC117
    3 mg/kg, single dose IV administration of 3BNC117
  • Biological: 10 mg/kg, single dose IV administration of 3BNC117
    10 mg/kg, single dose IV administration of 3BNC117
  • Experimental: Group 1, single dose IV of 3BNC117
    Group 1 (HIV-uninfected individuals): 1A (1 mg/kg, single dose, IV), 1B (3 mg/kg, single dose, IV), 1C (10 mg/kg, single dose, IV) and expansion subgroup 1D (10 mg/kg, single dose, IV).
    Interventions:
    • Biological: 1 mg/kg, single dose IV administration of 3BNC117
    • Biological: 3 mg/kg, single dose IV administration of 3BNC117
    • Biological: 10 mg/kg, single dose IV administration of 3BNC117
  • Experimental: Group 2, single dose IV of 3BNC117
    Group 2 (HIV-infected individuals, with HIV-1 RNA levels of 2,000-100,000 copies/ml), off ART): 2A (1 mg/kg, single dose, IV), 2B (3 mg/kg, single dose, IV), 2C (10 mg/kg, single dose, IV) and expansion subgroup 2D (10 mg/kg, single dose, IV)
    Interventions:
    • Biological: 1 mg/kg, single dose IV administration of 3BNC117
    • Biological: 3 mg/kg, single dose IV administration of 3BNC117
    • Biological: 10 mg/kg, single dose IV administration of 3BNC117
  • Experimental: Group 3 single dose IV of 3BNC117
    Group 3 (HIV-infected individuals, controllers with HIV-1 RNA levels of < 2,000 copies/ml and off ART): 10 mg/kg, single dose, IV
    Intervention: Biological: 10 mg/kg, single dose IV administration of 3BNC117
  • Experimental: Group 4 single dose IV of 3BNC117
    Group 4 (HIV-infected individuals, on ART with plasma HIV-1 RNA levels of 21-500 copies/ml): 10 mg/kg, single dose, IV
    Intervention: Biological: 10 mg/kg, single dose IV administration of 3BNC117
  • Experimental: Group 5 single dose IV of 3BNC117
    Group 5 (HIV-infected individuals, on ART with plasma HIV-1 RNA levels of 1-20 copies/ml): 10 mg/kg, single dose, IV
    Intervention: Biological: 10 mg/kg, single dose IV administration of 3BNC117
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
61
January 2016
January 2016   (final data collection date for primary outcome measure)

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 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 period

Groups 2 - 5 (HIV-infected):

  • Age 18 to 65
  • HIV-1 infection confirmed by ELISA and immunoblot
  • Group 2: Untreated HIV non-controllers (off ART for at least 8 weeks): HIV-1 RNA plasma level of 2,000 -100,000 copies/ml by standard assays, in 2 occasions, at least 1 week apart;
  • Group 3: Untreated HIV controllers (off ART for at least 8 weeks): HIV-1 RNA plasma level of < 2,000 copies/ml by standard assays, in 2 occasions, at least 1 week apart
  • Group 4: ART-treated with HIV-1 RNA plasma level of 21-500 copies/ml by standard assays in 2 occasions, at least 1 week apart, while on combination antiretroviral therapy
  • Group 5: ART treated with HIV-1 RNA plasma level of 1-20 copies/ml by a single copy assay in 2 occasions, at least 1 week apart, while on combination antiretroviral therapy
  • CD4 cell count > 300 cells/μl and CD4 nadir > 200 cell/μl
  • If 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 period.

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 infection
  • Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies)
  • Laboratory abnormalities in the parameters listed below:

    • Absolute neutrophil count equal to or less than 2,000 /mcL
    • Hemoglobin equal to or less than 12 gm/dL if female and 13.5 gm/dL if male
    • Platelet count equal to or less than 140,000 /mcL
    • ALT equal to or higher than 1.25 x ULN
    • AST equal to or higher than 1.25 x ULN
    • Total bilirubin equal to or higher than 1.1 ULN
    • Creatinine equal to or higher than 1.1 x ULN
    • Coagulation parameters (PT, PTT, INR) equal to or higher than 1.1 x ULN
  • Pregnancy or lactation
  • 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):

  • Have a 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 equal to or less than 1,300 / mcL
    • Hemoglobin equal to or less than 10 gm/dL
    • Platelet count equal to or less than 125,000
    • ALT equal to or higher than 2.0 x ULN
    • AST equal to or higher than 2.0 x ULN
    • Total bilirubin equal to or higher than 1.1 ULN
    • Creatinine equal to or higher than 1.1 x ULN
  • Coagulation parameters equal to or higher than 1.1 x ULN
  • Pregnancy or lactation
  • 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
  • Current ART regimen includes either maraviroc or enfuvirtide
Both
18 Years to 65 Years
Yes
United States
 
NCT02018510
MCA-0835
Yes
Rockefeller University
Rockefeller University
Not Provided
Not Provided
Rockefeller University
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP