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

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.

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Drug: 3BNC117-LS; Drug: 10-1074-LS

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • The Rockefeller University
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center Clinical Trials Unit-CLOSED SITE
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman School of Medicine University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Monoclonal Antibody; Drug: 10-1074-LS; Intravenous infusion of 10-1074-LS at 30mg/kg; Other Names: Monoclonal Antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Half-life	Half-life of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.	24 weeks
Grade 3 and Serious Adverse Events	The number of participants with treatment-related solicited and unsolicited grade 3 and serious adverse events (including confirmed laboratory abnormalities).	24 weeks
Peak Concentration	Peak concentration of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.	24 weeks
Area Under Curve	Area under curve of 3BNC117-LS and 10-1074-LS when administered intravenously and in combination to viremic HIV-infected individuals.	24 weeks
Maximum Decline in Plasma HIV-1 RNA Level	Maximum 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.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The number of adverse events that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.	24 weeks
Laboratory Abnormalities	The number of confirmed laboratory abnormalities that occur during the study follow up period after 3BNC117-LS and 10-1074-LS administration.	24 weeks
Anti-drug Antibodies	Number of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response.	24 weeks

Collaborators and Investigators

• Sponsor: Rockefeller University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of Pennsylvania; Weill Medical College of Cornell University
• Investigators: Principal Investigator: Marina Caskey, The Rockefeller University

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Actual): January 21, 2022
• Study Completion (Actual): February 11, 2022

Study Registration Dates

• First Submitted: January 30, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): June 26, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: 10-1074-LS; 3BNC117-LS; Broadly Neutralizing Antibody
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: MCA-0994; 1U01AI145921 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No