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Clinical Trials

MainTitle

3BNC117-LS First-in-Human Phase 1 Study

This study is currently recruiting participants. (see Contacts and Locations)

Verified August 2017 by Rockefeller University

Sponsor
Rockefeller University


Information provided by (Responsible Party)
Rockefeller University
ClinicalTrials.gov Identifier
NCT03254277

First received: August 11, 2017
Last updated: September 1, 2017
Last Verified: August 2017
History of Changes
Purpose

Purpose

This study is a phase 1, open label, dose-escalation study of the mAb 3BNC117-LS administered intravenously in HIV (human immunodeficiency virus)-uninfected individuals and HIV-infected individuals. The objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of a single infusion of 3BNC117-LS in HIV-uninfected and HIV-infected individuals.

Condition Intervention Phase
Human Immunodeficiency Virus

Drug : 3BNC117-LS
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 1, Dose Escalation, First-in-human Study of the Safety and Pharmacokinetics of 3BNC117-LS Administered Intravenously in HIV-infected and HIV-uninfected Individuals

Further study details as provided by Rockefeller University:

Primary Outcome Measures

  • The number of participants who experience adverse events within 2 weeks after 3BNC117-LS infusion in all study groups [ Time Frame: 2 weeks following the 3BNC117-LS infusion ]
    Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
  • Elimination half-life (t1/2) of 3BNC117-LS in all study groups [ Time Frame: 48 weeks ]
    Elimination half-life (t1/2) of 3BNC117-LS in all study groups
  • Clearance (CL/F) of 3BNC117-LS in all study groups [ Time Frame: 48 weeks ]
    Clearance (CL/F) of 3BNC117-LS in all study groups
  • Volume of distribution (Vz/F) of 3BNC117-LS in all study groups [ Time Frame: 48 weeks ]
    Volume of distribution (Vz/F) of 3BNC117-LS in all study groups
  • Area under the curve of 3BNC117-LS in all study groups [ Time Frame: 48 weeks ]
    Area under the curve of 3BNC117-LS in all study groups
  • Decay curve of 3BNC117-LS in all study groups [ Time Frame: 48 weeks ]
    Decay curve of 3BNC117-LS in all study groups
Secondary Outcome Measures:
  • Frequency of induced anti-3BNC117-LS antibodies in all study groups. [ Time Frame: 48 weeks ]
    Frequency of induced anti-3BNC117-LS antibodies in all study groups.
  • Levels of induced anti-3BNC117-LS antibodies in all study groups. [ Time Frame: 48 weeks ]
    Levels of induced anti-3BNC117-LS antibodies in all study groups.
  • The number of participants who experience adverse events during study follow-up [ Time Frame: 48 weeks ]
    Adverse events include signs, symptoms and laboratory abnormalities
Other Outcome Measures:
  • 3BNC117-LS levels in cervicovaginal and rectal fluids [ Time Frame: Day 0 and 2 weeks following 3BNC117-LS infusion ]
    3BNC117-LS levels in cervicovaginal and rectal fluids
  • The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals [ Time Frame: 48 weeks ]
    The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals
  • Analysis of escape viruses in individuals not on ART [ Time Frame: 48 weeks ]
    Phenotypic and genotypic analysis of escape viruses in individuals not on ART.
  • Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion. [ Time Frame: 48 weeks ]
    Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion.
  • Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion. [ Time Frame: 48 weeks ]
    Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion.
  • HIV-specific T and B cell immune responses following 3BNC117-LS infusion [ Time Frame: 48 weeks ]
    HIV-specific T and B cell immune responses following 3BNC117-LS infusion
  • T cell counts after 3BNC117-LS infusion [ Time Frame: 48 weeks ]
    Absolute and relative CD4 + and CD8+ T cell counts after 3BNC117-LS infusion.

Estimated Enrollment: 30
Study Start Date: August 31, 2017
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Group 1A
HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg.
Drug: 3BNC117-LS

Intravenous infusion of 3BNC117-LS

Other Name: Monoclonal Antibody
Experimental: Group 1B
HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
Drug: 3BNC117-LS

Intravenous infusion of 3BNC117-LS

Other Name: Monoclonal Antibody
Experimental: Group 1C
HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
Drug: 3BNC117-LS

Intravenous infusion of 3BNC117-LS

Other Name: Monoclonal Antibody
Experimental: Group 2B
HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
Drug: 3BNC117-LS

Intravenous infusion of 3BNC117-LS

Other Name: Monoclonal Antibody
Experimental: Group 2C
HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
Drug: 3BNC117-LS

Intravenous infusion of 3BNC117-LS

Other Name: Monoclonal Antibody

Detailed Description:

The proposed study is a Phase 1, open label, dose escalation cohort study of 3BNC117-LS administered intravenously in HIV-uninfected and HIV-1 infected participants.
Study participants will be administered a single intravenous infusion of 3BNC117-LS at one of three increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg) and will be followed for 48 weeks after 3BNC117-LS administration.
This trial will enroll 15 to 30 participants into 5 study groups.
First, eligible participants will be enrolled in Group 1A (n=3-6; HIV-uninfected, 3 mg/kg) and participants will be administered 3BNC117-LS at least one day apart. No more than 2 participants in Group 1A will be administered 3BNC117-LS in a given week.
Enrollment in Group 1B (n=3-6; HIV-uninfected, 10 mg/kg) and Group 2B (n=3-6; HIV-infected on or off ART (antiretroviral therapy), 10 mg/kg) will begin after participants enrolled in Group 1A reach day 42 with ≤ 1 dose limiting toxicity (DLT: any adverse event of grade 3 or greater toxicity, if the study investigators recognize a probable or definite attribution to 3BNC117-LS). Participants will be administered 3BNC117-LS at least one day apart.
Enrollment in Group 1C (n=3-6; HIV-uninfected, 30 mg/kg) will begin after participants enrolled in Group 1B reach day 42 with ≤ 1 DLT. The first 3 participants enrolled in Group 1C will be administered 3BNC117-LS at least one day apart, and no more than 2 participants will be administered 3BNC117-LS in a given week. After the first 3 participants enrolled in Group 1C reach day 42 with ≤ 1 DLT, the remaining 3 participants will be enrolled, and administered 3BNC117-LS at least one day apart.
Enrollment in Group 2C (n=3-6; HIV-infected on or off ART, 30 mg/kg) will begin after participants enrolled in Group 2B reach day 42 with ≤ 1 DLT. The first 3 participants enrolled in Group 2C will be administered 3BNC117-LS at least one day apart. After the first 3 participants enrolled in Group 2C reach day 42 with ≤ 1 DLT, the remaining 3 participants will be enrolled, and administered 3BNC117-LS at least one day apart.
Following 3BNC117-LS infusion, study participants will return for safety assessments at weeks 1, 2 and 4 following infusion, then bi-monthly or monthly until the end of study follow up.
Serum samples for PK (pharmacokinetic) measurements will be collected before 3BNC117-LS infusion, at the end of the infusion, and at multiple time points during study follow up.
Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS infusion (screen, pre-infusion and day 0) and at all follow up visits in Groups 2B and 2C.
All participants will be followed for 48 weeks after 3BNC117-LS infusion.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 65 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:
Groups 1A-1C (HIV-uninfected):

  1. Males and females, age 18 to 65
  2. Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
  3. If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.
    • Female study participants of reproductive potential are defined as pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.

Groups 2B-2C (HIV-infected):
  • Males and females, age 18 to 65.
  • HIV-1 infection confirmed by two laboratory assays.
  • HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays (ART-naïve or off ART due to intolerance or by choice), or on ART with HIV-1 plasma RNA levels < 20 copies/ml. HIV-1 RNA levels should be measured on 2 occasions, at least 1 week apart. At least one measurement must be performed within 49 days prior to enrollment (day 0).
  • Current CD4+ T cell count > 300 cells/μl.
  • If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.

  • Exclusion Criteria:

  • Groups 1A-1C (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 (such as autoimmune diseases) that in the opinion of the investigator would preclude participation.
  • Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
  • Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
  • Laboratory abnormalities in the parameters listed:
    • Absolute neutrophil count ≤ 1,500 cells/µL;
    • Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;
    • Platelet count ≤ 125,000 cells/µL;
    • Alanine transaminase (ALT) ≥ 1.25 x ULN;
    • Aspartate transaminase (AST) ≥ 1.25 x ULN;
    • Alkaline phosphatase ≥ 1.5 x ULN;
    • Total bilirubin > 1 x ULN;
    • Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.
  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to 3BNC117-LS infusion.
  • Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
  • History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
  • Individuals with known hypersensitivity to any constituent of the investigational product.
  • Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.

  • Groups 2B-2C (HIV-infected):
  • Have a history of AIDS-defining illness within 3 years prior to enrollment.
  • 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 (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
  • Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
  • Laboratory abnormalities in the parameters listed below:
    • Absolute neutrophil count ≤ 1,000 cells/μl;
    • Hemoglobin ≤ 10 gm/dL;
    • Platelet count ≤ 100,000 cells/μl;
    • ALT ≥ 1.5 x ULN;
    • AST ≥ 1.5 x ULN;
    • Alkaline phosphatase ≥ 1.5 x ULN;
    • Total bilirubin > 1 x ULN;
    • eGFR < 60 mL/min/1.73m2.
  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to 3BNC117-LS infusion.
  • Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
  • History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
  • Individuals with known hypersensitivity to any constituent of the investigational product.
  • Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.

    contacts and locations

    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: NCT03254277

    Contacts

    Contact:   Recruitment Specialist 800-782-2737 rucares@rockefeller.edu

    Locations

    United States, New York
    The Rockefeller University Recruiting
    New York, New York, United States, 10065
    Contact: Recruitment Specialist    800-782-2737    rucares@rockefeller.edu
    Principal Investigator: Yehuda Cohen, MD
    Sub-Investigator: Marina Caskey, MD
    Sub-Investigator: Allison Butler, NP

    Sponsors and Collaborators

    Rockefeller University

    Investigators

    Principal Investigator: Yehuda Cohen, MD The Rockefeller University
    More Information

    More Information


    Responsible Party: Rockefeller University  
    ClinicalTrials.gov Identifier: NCT03254277   History of Changes  
    Other Study ID Numbers: YCO-0946  
    Study First Received: August 11, 2017  
    Last Updated: September 1, 2017  

    Studies a U.S. FDA-regulated Drug Product: Yes  
    Studies a U.S. FDA-regulated Device Product: No  

    Keywords provided by Rockefeller University:

    Broadly Neutralizing Antibody
    3BNC117-LS
    First in Human
    Dose Escalation

    Additional relevant MeSH terms:
    Immunologic Deficiency Syndromes
    Acquired Immunodeficiency Syndrome
    HIV Infections
    Antibodies

    ClinicalTrials.gov processed this data on October 16, 2017
    This information is provided by ClinicalTrials.gov.