A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Rockefeller University
Sponsor:
Collaborators:
Weill Medical College of Cornell University
Brigham and Women's Hospital
University of Cologne
Information provided by (Responsible Party):
Rockefeller University
ClinicalTrials.gov Identifier:
NCT02018510
First received: December 17, 2013
Last updated: April 20, 2015
Last verified: April 2015
  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
Biological: 30 mg/kg, single dose IV administration of 3BNC117
Biological: 10 mg/kg, two doses IV of 3BNC117
Biological: 30 mg/kg, two doses IV 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 one or two intravenous infusions 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 one or two intravenous infusions 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 1A

HIV-uninfected individuals

1 mg/kg, single dose IV administration of 3BNC117

Biological: 1 mg/kg, single dose IV administration of 3BNC117
1 mg/kg, single dose IV administration of 3BNC117
Experimental: Groups 1B
HIV-uninfected individuals 3 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
Experimental: Group 1C
HIV-uninfected individuals 10 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 1D
HIV-uninfected individuals 10 mg/kg, two doses IV of 3BNC117
Biological: 10 mg/kg, two doses IV of 3BNC117
10 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
Experimental: Group 1E
HIV-uninfected individuals 30 mg/kg, single dose IV administration of 3BNC117
Biological: 30 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
Experimental: Group 1F
HIV-uninfected individuals 30 mg/kg, two doses IV of 3BNC117
Biological: 30 mg/kg, two doses IV of 3BNC117
30 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
Experimental: Group 2A

HIV-infected individuals on or off ART

1 mg/kg, single dose IV administration of 3BNC117

Biological: 1 mg/kg, single dose IV administration of 3BNC117
1 mg/kg, single dose IV administration of 3BNC117
Experimental: Group 2B
HIV-infected individuals on or off ART 3 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
Experimental: Group 2C
HIV-infected individuals on or off ART 10 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 2D
HIV-infected individuals on or off ART 30 mg/kg, single dose IV administration of 3BNC117
Biological: 30 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
Experimental: Group 2E
HIV-infected individuals off ART, VL 2,000-100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Biological: 30 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
Experimental: Group 3
HIV-infected individuals off ART, VL < 2,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Biological: 30 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
Experimental: Group 4
HIV-infected individuals on ART, VL < 100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Biological: 30 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
Experimental: Group 5A
HIV-infected individuals on ART, VL < 20 copies/ml 10 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 5B
HIV-infected individuals on ART, VL < 20 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Biological: 30 mg/kg, single dose IV administration of 3BNC117
30 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02018510

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Brian Engelson    617-525-7327    BENGELSON@partners.org   
Principal Investigator: Lindsey Baden, MD         
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         
Weill Cornell Medical Center Recruiting
New York, New York, United States, 10065
Contact: Kirsis Ham    212-746-4177    kah9003@med.cornell.edu   
Principal Investigator: Leah Burke, MD         
Germany
University of Cologne Recruiting
Cologne, Germany, 50937
Contact: Gisela Kremer, RN    +41-221-478-3324    gisela.kremer@uk-koeln.de   
Principal Investigator: Gerd Kaetkenheuer, MD         
Sponsors and Collaborators
Rockefeller University
Weill Medical College of Cornell University
Brigham and Women's Hospital
University of Cologne
Investigators
Principal Investigator: Marina Caskey, MD Rockefeller Univesrity
  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: April 20, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Rockefeller University:
Healthy Volunteers
HIV

ClinicalTrials.gov processed this record on September 02, 2015