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3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04250636
Recruitment Status : Not yet recruiting
First Posted : January 31, 2020
Last Update Posted : February 6, 2020
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Weill Medical College of Cornell University
Perelman School of Medicine University of Pennsylvania
Information provided by (Responsible Party):
Rockefeller University

Brief Summary:
The proposed study is a phase 1, open label, single arm study to evaluate the safety, pharmacokinetics and antiviral activity of single intravenous infusions of 3BNC117-LS and 10-1074-LS, each monoclonal antibody (mAb) dosed at 30 mg/kg in viremic human immunodeficiency virus (HIV)-infected individuals.

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

Detailed Description:

The proposed study is a phase 1, open label, single arm study to evaluate the safety, pharmacokinetics and antiviral activity of single intravenous infusions of 3BNC117-LS and 10-1074-LS in viremic HIV-infected individuals.

Ten eligible participants will be enrolled sequentially in the study and will receive each mAb, dosed at 30 mg/kg intravenously and in sequence on study day 0. Following mAb administration, study participants will return for safety assessments on days 1 and 3, and weeks 1, 2, 3 and 4 following dosing, then bi-weekly or monthly until the end of study follow up. All participants will be followed for 24 weeks after 3BNC117-LS and 10-1074-LS administration.

Safety assessments will be performed at multiple time points following 3BNC117-LS and 10-1074-LS infusions. Serum samples for pharmacokinetic (PK) measurements will be collected before and at the end each mAb infusion 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 3BNC117-LS and 10-1074-LS infusions (screen and day 0) and at every follow up visit. T cell subsets will also be monitored during study follow up. Assessments will also include measurement of anti-drug antibody responses and sequencing of plasma envelope before infusions and after viral rebound (first time point after viremia nadir is reached and viral load (VL) is > 1,000 copies/ml).

Participants will be advised and encouraged to start antiretroviral therapy (ART) within 4 weeks of receiving 3BNC117-LS and 10-1074-LS infusions or sooner if: VL fails to decrease by > 0.5 log10 copies/ml within 2 weeks of antibody infusions, VL increases > 0.5 log10 copies/ml between weekly measurements or significant T-cell decline (confirmed CD4+ T cells < 200 cells/μl) is noted.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Single Arm Study of the Safety, Pharmacokinetics and Antiretroviral Activity of the Combination of 3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals.
Estimated Study Start Date : February 28, 2020
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Study Participants
HIV-infected individuals, off ART, and with plasma HIV-1 RNA levels between 500 and 100,000 copies/ml by standard assays. Study participants will receive a single intravenous infusion of 3BNC117-LS and a single infusion of 10-1074-LS. The antibodies will be administered sequentially and dosed at 30 mg/kg.
Drug: 3BNC117-LS
Intravenous infusion of 3BNC117-LS at 30mg/kg
Other Name: Monoclonal Antibody

Drug: 10-1074-LS
Intravenous infusion of 10-1074-LS at 30mg/kg
Other Name: Monoclonal Antibody




Primary Outcome Measures :
  1. Grade 3 and serious adverse events [ Time Frame: 24 weeks ]
    The number of participants with treatment-related solicited and unsolicited grade 3 and serious adverse events (including confirmed laboratory abnormalities).

  2. Peak concentration [ Time Frame: 24 weeks ]
    Peak concentration of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.

  3. Half-life [ Time Frame: 24 weeks ]
    Half-life of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.

  4. Area under curve [ Time Frame: 24 weeks ]
    Area under curve of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.

  5. Clearance Rate [ Time Frame: 24 weeks ]
    Clearance rate of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.

  6. The decline in plasma HIV-1 RNA level [ Time Frame: 4 weeks ]
    - The decline in plasma HIV-1 RNA level after 3BNC117-LS plus 10-1074-LS intravenous infusions in viremic HIV-infected individuals through week 4 after infusions.


Secondary Outcome Measures :
  1. Anti-drug Antibodies [ Time Frame: 24 weeks ]
    Proportion of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response.

  2. Adverse Events [ Time Frame: 24 weeks ]
    The number of adverse events that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.

  3. Laboratory Abnormalities [ Time Frame: 24 weeks ]
    The number of confirmed laboratory abnormalities that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females, >18 years of age.
  2. Confirmed HIV-1 infection.
  3. Off ART for at least 4 weeks with a HIV-1 plasma RNA level between 500 and 100,000 copies/mL (ART-naïve or off ART due to intolerance or by choice).
  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 six months after 3BNC117-LS and 10-1074-LS administration.

Exclusion Criteria:

  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 > 1.25 x ULN;
    • eGFR < 60 mL/min/1.73m2.
  6. Pregnancy or lactation.
  7. Any vaccination within 14 days prior to mAb infusions, except for influenza vaccine.
  8. 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.
  9. Receipt of any experimental HIV vaccine or anti-HIV monoclonal antibody therapy 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 products.

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): NCT04250636


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

Locations
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United States, New York
Weill Cornell Medical Center Clinical Trials Unit
New York, New York, United States, 10021
Contact: Timothy Wilkin, MD    212-746-4177    tiw2001@med.cornell.edu   
The Rockefeller University
New York, New York, United States, 10065
Contact: Recruitment Specialist, MD    800-782-2737    rucares@rockefeller.edu   
Principal Investigator: Marina Caskey, MD         
United States, Pennsylvania
Perelman School of Medicine University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Contact: Pablo Tebas, MD    215-349-8091    pablo.tebas@uphs.upenn.edu   
Sponsors and Collaborators
Rockefeller University
National Institute of Allergy and Infectious Diseases (NIAID)
Weill Medical College of Cornell University
Perelman School of Medicine University of Pennsylvania
Investigators
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Principal Investigator: Marina Caskey The Rockefeller University

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Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT04250636    
Other Study ID Numbers: MCA-0994
1U01AI145921 ( U.S. NIH Grant/Contract )
First Posted: January 31, 2020    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:
3BNC117-LS
10-1074-LS
Broadly Neutralizing Antibody
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
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents