Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02018510
Recruitment Status : Completed
First Posted : December 23, 2013
Last Update Posted : December 26, 2016
Sponsor:
Collaborators:
Weill Medical College of Cornell University
Brigham and Women's Hospital
University of Cologne
Information provided by (Responsible Party):
Rockefeller University

Tracking Information
First Submitted Date  ICMJE December 17, 2013
First Posted Date  ICMJE December 23, 2013
Last Update Posted Date December 26, 2016
Study Start Date  ICMJE January 2014
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 15, 2014)
Safety and tolerability [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
Safety and tolerability [ Time Frame: 24 weeks ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2014)
Pharmacokinetic profile [ Time Frame: 24 hours post infusion ]
To determine the pharmacokinetic profile of one or two intravenous infusions of 3BNC117 in HIV-uninfected and HIV-infected subjects.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
Pharmacokinetic profile [ Time Frame: 24 hours post infusion ]
To determine the pharmacokinetic profile of a single intravenous administration of 3BNC117 in HIV-uninfected and HIV-infected subjects.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Healthy
  • HIV
Intervention  ICMJE
  • 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
  • Biological: 30 mg/kg, single dose IV administration of 3BNC117
    30 mg/kg, single dose IV administration of 3BNC117
  • Biological: 10 mg/kg, two doses IV of 3BNC117
    10 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
  • Biological: 30 mg/kg, two doses IV of 3BNC117
    30 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
Study Arms  ICMJE
  • Experimental: Group 1A

    HIV-uninfected individuals

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

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

    HIV-infected individuals on or off ART

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

    Intervention: Biological: 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
    Intervention: Biological: 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
    Intervention: Biological: 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
    Intervention: Biological: 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
    Intervention: Biological: 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
    Intervention: Biological: 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
    Intervention: Biological: 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
    Intervention: Biological: 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
    Intervention: Biological: 30 mg/kg, single dose IV administration of 3BNC117
Publications * Schoofs T, Klein F, Braunschweig M, Kreider EF, Feldmann A, Nogueira L, Oliveira T, Lorenzi JC, Parrish EH, Learn GH, West AP Jr, Bjorkman PJ, Schlesinger SJ, Seaman MS, Czartoski J, McElrath MJ, Pfeifer N, Hahn BH, Caskey M, Nussenzweig MC. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science. 2016 May 20;352(6288):997-1001. doi: 10.1126/science.aaf0972. Epub 2016 May 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 1, 2016)
49
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2013)
61
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02018510
Other Study ID Numbers  ICMJE MCA-0835
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rockefeller University
Study Sponsor  ICMJE Rockefeller University
Collaborators  ICMJE
  • Weill Medical College of Cornell University
  • Brigham and Women's Hospital
  • University of Cologne
Investigators  ICMJE
Principal Investigator: Marina Caskey, MD Rockefeller Univesrity
PRS Account Rockefeller University
Verification Date December 2016

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