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

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ClinicalTrials.gov Identifier: NCT03554408
Recruitment Status : Recruiting
First Posted : June 13, 2018
Last Update Posted : June 13, 2018
Sponsor:
Information provided by (Responsible Party):
Rockefeller University

Brief Summary:
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 or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: 10-1074-LS Drug: 3BNC117-LS Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Groups 1A, 1B, 4A, and 4B are double-blinded; All other arms are open label.
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
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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 6A
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 6B
HIV-infected individuals (off ART) will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion 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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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 weeks ]
    Elimination half-life (t1/2) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  4. The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups. [ Time Frame: 48 weeks ]
    The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  5. 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 weeks ]
    The volume of distribution (Vz) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups

  6. Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups. [ Time Frame: 48 weeks ]
    Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  7. Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups. [ Time Frame: 48 weeks ]
    Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.


Secondary Outcome Measures :
  1. Frequency of induced anti-10-1074-LS antibodies [ Time Frame: 48 weeks ]
    Frequency of induced anti-10-1074-LS antibodies

  2. Level of induced anti-10-1074-LS antibodies [ Time Frame: 48 weeks ]
    Level of induced anti-10-1074-LS antibodies

  3. Frequency of induced anti-3BNC117-LS antibodies [ Time Frame: 48 weeks ]
    Frequency of induced anti-3BNC117-LS antibodies

  4. Level of induced anti-3BNC117-LS antibodies [ Time Frame: 48 weeks ]
    Level of induced anti-3BNC117-LS antibodies

  5. 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 weeks ]
    Adverse events include signs, symptoms and laboratory abnormalities



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Groups 1A-1B, 2A-2C, 4A-4B, 5 (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, 6A-6B (HIV-infected):

  • Males and females, age 18 to 65.
  • Confirmed HIV-1 infection.
  • Groups 3B-3C and 6A: HIV-infected individuals on ART with HIV-1 plasma RNA levels < 50 copies/mL.
  • Group 6B: 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).
  • 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 (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, 6A-6B (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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   
Sub-Investigator: Marina Caskey, MD         
Principal Investigator: Yehuda Cohen, MD         
Sub-Investigator: Allison Butler, NP         
Sponsors and Collaborators
Rockefeller University
Investigators
Principal Investigator: Yehuda Cohen, MD The Rockefeller University

Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT03554408     History of Changes
Other Study ID Numbers: YCO-0971
First Posted: June 13, 2018    Key Record Dates
Last Update Posted: June 13, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
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
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs