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.
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
  Purpose

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.


Condition Intervention Phase
Healthy
HIV
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
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Rockefeller University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 61
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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 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)
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 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
Biological: 10 mg/kg, single dose IV administration of 3BNC117
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
Biological: 10 mg/kg, single dose IV administration of 3BNC117
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
Biological: 10 mg/kg, single dose IV administration of 3BNC117
10 mg/kg, single dose IV administration of 3BNC117

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02018510

Locations
United States, New York
The Rockefeller University Recruiting
New York, New York, United States, 10065
Contact: Lauren Corregano    800-782-2737    rucares@rockefeller.edu   
Principal Investigator: Marina Caskey, MD         
Sponsors and Collaborators
Rockefeller University
  More Information

No publications provided

Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT02018510     History of Changes
Other Study ID Numbers: MCA-0835
Study First Received: December 17, 2013
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Rockefeller University:
Healthy Volunteers
HIV

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014