Clinical Trials

MainTitle

First-in-human Study of 10-1074-LS Alone and in Combination With 3BNC117-LS

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

Verified June 2019 by Rockefeller University

Sponsor
Rockefeller University


Information provided by (Responsible Party)
Rockefeller University
ClinicalTrials.gov Identifier
NCT03554408

First received: May 31, 2018
Last updated: June 26, 2019
Last Verified: June 2019
History of Changes
Purpose

Purpose

This first clinical study of 10-1074-LS will evaluate its safety, tolerability and pharmacokinetics profile when administered alone or in combination with 3BNC117-LS to HIV (human immunodeficiency virus) -infected and HIV-uninfected individuals.

Condition Intervention Phase
Human Immunodeficiency Virus

Drug : 10-1074-LS
Drug : 3BNC117-LS
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 1, Dose Escalation, First-in-human Study of the Safety and Pharmacokinetics of the Subcutaneous and Intravenous Administration of 10-1074-LS Alone and in Combination With 3BNC117-LS 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 10-1074-LS intravenous infusions and subcutaneous injections. [ Time Frame: 2 weeks ]
    Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
  • The number of participants who experience adverse events within 2 weeks after 10-1074-LS and 3BNC117-LS intravenous infusions and subcutaneous injections. [ Time Frame: 2 weeks ]
    Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
  • Elimination half-life (t1/2) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups. [ Time Frame: 48-72 weeks ]
    Elimination half-life (t1/2) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.
  • The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups. [ Time Frame: 48-72 weeks ]
    The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.
  • The volume of distribution (Vz) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups [ Time Frame: 48-72 weeks ]
    The volume of distribution (Vz) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups
  • Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups. [ Time Frame: 48-72 weeks ]
    Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.
  • Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups. [ Time Frame: 48-72 weeks ]
    Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.
Secondary Outcome Measures:
  • Frequency of induced anti-10-1074-LS antibodies [ Time Frame: 48-72 weeks ]
    Frequency of induced anti-10-1074-LS antibodies
  • Level of induced anti-10-1074-LS antibodies [ Time Frame: 48-72 weeks ]
    Level of induced anti-10-1074-LS antibodies
  • Frequency of induced anti-3BNC117-LS antibodies [ Time Frame: 48-72 weeks ]
    Frequency of induced anti-3BNC117-LS antibodies
  • Level of induced anti-3BNC117-LS antibodies [ Time Frame: 48-72 weeks ]
    Level of induced anti-3BNC117-LS antibodies
  • The number of participants that experience who experience adverse events during the study follow up period after 10-1074-LS and/or 3BNC117-LS administration in all study groups. [ Time Frame: 48-72 weeks ]
    Adverse events include signs, symptoms and laboratory abnormalities

Estimated Enrollment: 75
Study Start Date: June 20, 2018
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Group 1A
HIV-uninfected individuals will be administered one 1 mL (approximately 150 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.
Drug: 10-1074-LS

Subcutaneous injection of 10-1074-LS

Other Name: Monoclonal antibody
Experimental: Group 1B
HIV-uninfected individuals will be administered one 2 mL (approximately 300 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.
Drug: 10-1074-LS

Subcutaneous injection of 10-1074-LS

Other Name: Monoclonal antibody
Experimental: Group 2A
HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 3 mg/kg.
Drug: 10-1074-LS

Intravenous infusion of 10-1074-LS

Other Name: Monoclonal antibody
Experimental: Group 2B
HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg.
Drug: 10-1074-LS

Intravenous infusion of 10-1074-LS

Other Name: Monoclonal antibody
Experimental: Group 2C
HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.
Drug: 10-1074-LS

Intravenous infusion of 10-1074-LS

Other Name: Monoclonal antibody
Experimental: Group 3B
HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg
Drug: 10-1074-LS

Intravenous infusion of 10-1074-LS

Other Name: Monoclonal antibody
Experimental: Group 3C
HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.
Drug: 10-1074-LS

Intravenous infusion of 10-1074-LS

Other Name: Monoclonal antibody
Experimental: Group 4A
HIV-uninfected individuals will be administered one 2 mL (approximately 150 mg of each mAb) subcutaneous injection of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.
Drug: 10-1074-LS

Subcutaneous injection of 10-1074-LS

Other Name: Monoclonal antibody
Drug: 3BNC117-LS

Subcutaneous injection of 3BNC117-LS

Other Name: Monoclonal antibody
Experimental: Group 4B
HIV-uninfected individuals will be administered two 2 mL (approximately 300 mg of each mAb) subcutaneous injections of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.
Drug: 10-1074-LS

Subcutaneous injection of 10-1074-LS

Other Name: Monoclonal antibody
Drug: 3BNC117-LS

Subcutaneous injection of 3BNC117-LS

Other Name: Monoclonal antibody
Experimental: Group 5
HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.
Drug: 10-1074-LS

Intravenous infusion of 10-1074-LS

Other Name: Monoclonal antibody
Drug: 3BNC117-LS

Intravenous infusion of 3BNC117-LS

Other Name: Monoclonal antibody
Experimental: Group 6
HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.
Drug: 10-1074-LS

Intravenous infusion of 10-1074-LS

Other Name: Monoclonal antibody
Drug: 3BNC117-LS

Intravenous infusion of 3BNC117-LS

Other Name: Monoclonal antibody
Experimental: Group 7
HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (100 mg) admixed with 3BNC117-LS (200 mg) (2 mL) at weeks 0, 12, and 24.
Drug: 10-1074-LS

Subcutaneous injection of 10-1074-LS

Other Name: Monoclonal antibody
Drug: 3BNC117-LS

Subcutaneous injection of 3BNC117-LS

Other Name: Monoclonal antibody
Experimental: Group 8
HIV-infected individuals (on ART) will be administered three subcutaneous injections of 10-1074-LS (75 mg) admixed with 3BNC117-LS (225 mg) (2 mL) at weeks 0, 12, and 24.
Drug: 10-1074-LS

Subcutaneous injection of 10-1074-LS

Other Name: Monoclonal antibody
Drug: 3BNC117-LS

Subcutaneous injection of 3BNC117-LS

Other Name: Monoclonal antibody
Experimental: Group 9
HIV-infected individuals (on ART) will be administered three subcutaneous injections of 10-1074-LS (60 mg) admixed with 3BNC117-LS (250 mg) (2 mL) at weeks 0, 12, and 24.
Drug: 10-1074-LS

Subcutaneous injection of 10-1074-LS

Other Name: Monoclonal antibody
Drug: 3BNC117-LS

Subcutaneous injection of 3BNC117-LS

Other Name: Monoclonal antibody

Detailed Description:

The proposed study is a Phase 1, dose escalation cohort study of 10-1074-LS alone or in combination with 3BNC117-LS, administered intravenously and subcutaneously in HIV uninfected and HIV-1 infected individuals.
Study participants will be administered a single intravenous infusion of 10-1074-LS at 3, 10 or 30 mg/kg, single infusions of the combination of 10-1074-LS and 3BNC117-LS, each dosed at 30 mg/kg, or subcutaneous injections of 10-1074-LS alone or in combination with 3BNC117-LS, and three subcutaneous injections of 10-1074-LS in combination with 3BNC117-LS at three dose ratios. The first four groups administered subcutaneous injections of the product(s) will be randomized, double-blinded, and placebo-controlled to assess potential differences in safety and tolerability of the antibody formulation versus the formulation buffer alone. In the dose ratio portion of the study, participants will be randomized into one of three groups, but the products will be administered in an open-label manner. Groups administered intravenous infusions will be enrolled in an open-label manner.
PART A
Group 1A (n=8) - HIV-uninfected individuals will be administered one 1 mL (approximately 150 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.
Group 1B (n=8) - HIV-uninfected individuals will be administered one 2 mL (approximately 300 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.
Group 2A (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 3 mg/kg.
Group 2B (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg.
Group 2C (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.
Group 3B (n=3) - HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg.
Group 3C (n=3) - HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.
PART B
Part B will begin after the Safety Monitoring Committee (SMC) evaluates available safety data from Part A, as detailed below. The SMC will also review available safety data with 3BNC117-LS administered intravenously collected under protocol YCO-0946 prior to enrollment in Part B of this study. The SMC will also review subcutaneous dosing at approximately 150 mg (1 mL) and 300 mg (2 mL), collected under IND 131873 when available and prior to enrollment in Part B of this study.
Group 4A (n=8) - HIV-uninfected individuals will be administered one 2 mL (approximately 150 mg of each mAb) subcutaneous injection of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.
Group 4B (n=8) - HIV-uninfected individuals will be administered two 2 mL (approximately 300 mg of each mAb) subcutaneous injections of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.
Group 5 (n=5) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.
Group 6 (n=5) - HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.
Group 7 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (100 mg) admixed with 3BNC117-LS (200 mg) (2 mL).
Group 8 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (75 mg) admixed with 3BNC117-LS (225 mg) (2 mL).
Group 9 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (60 mg) admixed with 3BNC117-LS (240 mg) (2 mL).
Following mAb or placebo administration, study participants will return for safety assessments on days 1 and 3, and weeks 1, 2 and 4 following each dose, then bi-monthly or monthly until the end of study follow up.
All participants will be followed for 48 weeks after last mAb or placebo administration. Serum samples for PK measurements will be collected before and at the end each mAb or placebo administration and at multiple subsequent time points during study follow up.
Samples will also be collected for measurement of HIV-1 plasma RNA levels before 10-1074-LS and 3BNC117-LS infusions and at follow up visits according to protocol.

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-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (HIV-uninfected):

  • Males and females, age 18 to 65
  • Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
  • 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 nine months after 10-1074-LS and/or 3BNC117-LS administration.
  • 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 3B-3C, 6 (HIV-infected):
  • Males and females, age 18 to 65.
  • Confirmed HIV-1 infection.
  • HIV-infected individuals on ART with HIV-1 plasma RNA levels < 50 copies/mL.
  • 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 nine months after 10-1074-LS and/or 3BNC117-LS administration.


Exclusion Criteria:

    Groups 1A-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (HIV-uninfected):
  • Confirmed HIV-1 or HIV-2 infection.
  • Weight > 110 kg (subcutaneous groups only: 1A-1B, 4A-4B).
  • History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant
  • 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;
  • ALT ≥ 1.25 x ULN;
  • AST ≥ 1.25 x ULN;
  • Alkaline phosphatase ≥ 1.5 x ULN;by the trial physician within the last 6 months.
  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to mAb infusions.
  • 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 products.
  • 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 3B-3C, 6 (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 MAb infusions.
  • 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 products.
  • 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: NCT03554408

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: Marina Caskey, MD
Sub-Investigator: Allison Butler, NP

Sponsors and Collaborators

Rockefeller University

Investigators

Principal Investigator: Marina Caskey, MD The Rockefeller University
More Information

More Information


Responsible Party: Rockefeller University  
ClinicalTrials.gov Identifier: NCT03554408   History of Changes  
Other Study ID Numbers: YCO-0971  
Study First Received: May 31, 2018  
Last Updated: June 26, 2019  
Individual Participant Data    
Plan to Share IPD: No  

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

Keywords provided by Rockefeller University:

10-1074-LS
3BNC117-LS
First in Human
Dose Escalation

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Immunological

ClinicalTrials.gov processed this data on July 22, 2019
This information is provided by ClinicalTrials.gov.