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

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: NCT03254277
Recruitment Status : Active, not recruiting
First Posted : August 18, 2017
Last Update Posted : February 6, 2020
Sponsor:
Information provided by (Responsible Party):
Rockefeller University

Brief Summary:
The proposed study is a phase 1 study of the mAb 3BNC117-LS administered intravenously in HIV uninfected individuals and HIV-infected individuals, and subcutaneously in HIV-uninfected individuals.The objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of a single administration of 3BNC117-LS.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: 3BNC117-LS Drug: Placebo Phase 1

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.

This study consists of two parts. In part A, study participants will be enrolled in an open label manner to receive a single intravenous infusion of 3BNC117-LS at one of three increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg). Participants in Part B will also receive a single administration of 3BNC117-LS, however, the product administered in Part B of the study derives from a new manufacturing lot. The manufacturing lot used in Part A had incomplete glycosylation of the 3BNC117-LS light chain, which has been corrected in the new lot. Participants in Part B will receive 3BNC117-LS intravenously at 30 mg/kg in an open label manner (HIV-uninfected and HIV-infected) or will be randomized to receive a subcutaneous injection of 3BNC117-LS or placebo in a double-blinded fashion (HIV-uninfected only).

Part A has already been enrolled with 21 participants. Part B has a planned enrollment of 22 participants.

Part A

  • Group 1A (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg.
  • Group 1B (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
  • Group 1C (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
  • Group 2B (n=6) - 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.
  • Group 2C (n=6) - 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.

Part B

  • Group 1D (n=3) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
  • Group 2D (n=3) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
  • Group 1E (n=8) - HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
  • Group 1F (n=8) - HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.

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 administration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 1 First-in-human Study of the Safety and Pharmacokinetics of 3BNC117-LS in HIV-infected and HIV-uninfected Individuals
Actual Study Start Date : September 13, 2017
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 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 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

Experimental: Group 1D
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 2D
HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 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

Experimental: Group 1E
HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
Drug: 3BNC117-LS
Intravenous infusion of 3BNC117-LS
Other Name: Monoclonal Antibody

Drug: Placebo
Placebo

Experimental: Group 1F
HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
Drug: 3BNC117-LS
Intravenous infusion of 3BNC117-LS
Other Name: Monoclonal Antibody

Drug: Placebo
Placebo




Primary Outcome Measures :
  1. 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.

  2. 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

  3. Clearance (CL/F) of 3BNC117-LS in all study groups [ Time Frame: 48 weeks ]
    Clearance (CL/F) of 3BNC117-LS in all study groups

  4. 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

  5. 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

  6. 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 :
  1. 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.

  2. 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.

  3. 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:
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. T cell counts after 3BNC117-LS infusion [ Time Frame: 48 weeks ]
    Absolute and relative CD4 + and CD8+ T cell counts after 3BNC117-LS infusion.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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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-1F (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-2D (HIV-infected):

  1. Males and females, age 18 to 65.
  2. HIV-1 infection confirmed by two laboratory assays.
  3. 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). Group 2D will only enroll HIV-infected individuals on ART.
  4. Current CD4+ T cell count > 300 cells/μl.
  5. 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-1F (HIV-uninfected):

  1. Confirmed HIV-1 or HIV-2 infection.
  2. 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.
  3. Any clinically significant acute or chronic medical condition (such as autoimmune diseases) that in the opinion of the investigator would preclude participation.
  4. Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
  5. 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.
  6. 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.
  7. Pregnancy or lactation.
  8. Any vaccination within 14 days prior to 3BNC117-LS infusion.
  9. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
  10. History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
  11. Individuals with known hypersensitivity to any constituent of the investigational product.
  12. 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-2D (HIV-infected):

  1. Have a history of AIDS-defining illness within 3 years prior to enrollment.
  2. History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
  3. 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.
  4. 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.
  5. 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.
  6. Pregnancy or lactation.
  7. Any vaccination within 14 days prior to 3BNC117-LS infusion.
  8. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
  9. History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
  10. Individuals with known hypersensitivity to any constituent of the investigational product.
  11. 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): NCT03254277


Locations
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United States, New York
The Rockefeller University
New York, New York, United States, 10065
Sponsors and Collaborators
Rockefeller University
Investigators
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Principal Investigator: Marina Caskey, MD The Rockefeller University

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Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT03254277    
Other Study ID Numbers: YCO-0946
First Posted: August 18, 2017    Key Record Dates
Last Update Posted: February 6, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs