Broadly Neutralizing Antibodies 3BNC117-LS & 10-1074-LS to Prevent Relapse During ATI

NCT05079451 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: A536437546
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Participants will receive an infusion of both study drugs (3BNC117-LS and 10-1074-LS) and will discontinue antiretroviral therapy (which is the treatment for HIV) two days later. Participants will receive a second dose of the first study drug (3BNC117-LS) at week 12 if the HIV infection is maintained and participants remain off of antiretroviral therapy. The study hypothesizes that intravenous infusions (which means medication is delivered directly into a participant's vein) of the combination of study drugs will be safe and well tolerated, will maintain control of the HIV infection without antiretroviral therapy, and may be associated with a decrease in HIV found in cells that were previously infected with HIV but not actively producing HIV in the body.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Occurrence of Grade ≥3 systemic AE related to combination of 3BNC117-LS and 10-1074-LS or premature study treatment discontinuation due to an AE (regardless of grade) that is related to combination of 3BNC117-LS and 10-1074-LS.

  72 weeks

• Viral rebound defined as confirmed HIV-1 RNA >200 copies/mL at or prior to week 24 of ART discontinuation.

  24 weeks

Secondary Outcomes (9)

• Actual body exposure to drug after administration of a dose of the drug (known as the "Area under the curve (AUC)") of weeks 0-24 for 3BNC117-LS and 10-1074-LS.

  72 weeks

• Actual body exposure to drug after administration of a dose of the drug (known as the "Area under the curve (AUC)") of weeks 0-infinity for 3BNC117-LS and 10-1074-LS.

  72 weeks

• Frequency of induced anti-study drug antibodies (ADA).

  72 weeks

• CD4+ cell counts (cells/mm3) through entire study follow-up.

  72 weeks

• Viral suppression (defined as plasma HIV-1 RNA levels <50 copies/mL) at and prior to week 24 after ART discontinuation

  24 weeks

Study Arms (1)

Study Participants

EXPERIMENTAL

Participants will receive an infusion of both study drugs (3BNC117-LS and 10-1074-LS) and will then discontinue antiretroviral therapy two days later.

Drug: 3BNC117-LS; Drug: 10-1074-LS

Interventions

3BNC117-LS DRUG

3BNC117-LS will be administered by intravenous infusion (directly into the participants vein) over a period of 30 to 60 minutes. The total time needed to administer the study drug may be longer, based on factors such as participant tolerance. The participant's dose will be calculated using their most current weight on record.

Study Participants

10-1074-LS DRUG

10-1074-LS will be administered by intravenous infusion (directly into the participants vein) over a period of 30 to 60 minutes. The total time needed to administer the study drug may be longer, based on factors such as participant tolerance. The participant's dose will be calculated using their most current weight on record.

Study Participants

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness of participant to provide informed consent to enter the Screening and Pre-Entry segment of the study.
• Individuals age ≥18 to ≤70 years.
• Weight greater than or equal to 50 kg (110 pounds) and less than or equal to 115 kg (253.5 pounds).
• Documented HIV-1 infection.
• For participants who can become pregnant, a negative pregnancy test at Screening must be obtained.
• For participants who can become pregnant, participant must agree to use two methods of contraception.
• Participants who can impregnate a partner and who are engaging in sexual activity that could lead to pregnancy must agree to use condoms from 10 days prior to the first dose of study drugs, while receiving the study drugs, and for 12 months after the last dose of study drug to avoid impregnating a partner who can get pregnant.
• Willingness to use barrier protection (male or female) during sexual activity.

You may not qualify if:

• \. Currently breastfeeding or pregnancy.
• On stable suppressive Antiretroviral Therapy (ART) for at least 48 weeks prior to Step 1 study entry with no interruption of ART for 7 consecutive days or longer in the 48 weeks prior to entry in Step 1.
• If on an NNRTI-based regimen, willing to switch to an integrase inhibitor-based regimen at least 4 weeks prior to discontinuing ART.
• CD4+ cell count \>450 cells/µL obtained within 90 days prior to study Step 1 entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
• CD4+ cell % ≥15% obtained within 90 days prior to study Step 1 entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
• Nadir CD4+ cell count ≥200 cells/µL. (NOTE: If documentation is not available, then participant recall is acceptable.)
• Plasma HIV-1 RNA levels of \<50 copies/mL for at least 48 weeks prior to Step 1 entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent (NOTE: At least two viral load measurements within 48 weeks prior to the Step 0 screening visit must be available for review. A single plasma HIV-1 RNA \>50 copies/mL but \<200 copies/mL that is followed by an HIV-1 RNA \<50 copies/mL is permitted.)
• BNC117-LS IC90 less than 1 mcg/mL and MPI \>98% in PBMCs or plasma with the Monogram PhenoSense assay. (NOTE: Monogram PhenoSense assay obtained for eligibility to other clinical trials may be used for eligibility.)
• LS IC90 less than 1 mcg/mL and MPI \>98% in PBMCs or plasma with the Monogram PhenoSense assay. (NOTE: Monogram PhenoSense assay obtained for eligibility to other clinical trials may be used for eligibility.)
• The following laboratory values obtained within 90 days prior to Step 1 entry by any US laboratory that has a CLIA certification or its equivalent:
• absolute neutrophil count (ANC) ˃1,000/mm3
• hemoglobin \>10 g/dL
• platelet count ˃100,000/mm3
• eGFR ≥60 mL/min/1.73m2
• AST (SGOT), ALT (SGPT), and total bilirubin \<1.5 x ULN

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Rockefeller University: collaborator

Study Sites (1)

Alabama CRS

Birmingham, Alabama, 35222, United States

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Katharine J Bar, M.D.

  University of Pennsylvania

  STUDY CHAIR

• Marina Caskey, M.D.

  The Rockefeller University Non-Network CRS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Open-label, single-arm, multi-step study

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: October 15, 2021
• Study Start: January 1, 2024
• Primary Completion: January 15, 2024
• Study Completion: February 15, 2024
• Last Updated: September 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

US (1)