Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1

NCT03739996 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ACTG A535730005
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 18

Brief Summary

The purpose of this study was to assess the safety, tolerability, antiviral activity, and pharmacokinetics of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody VRC-HIVMAB075-00-AB (VRC07-523LS), in adults living with HIV-1 with suppressed plasma viremia.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) or Premature Discontinuation Due to an AE (Regardless of Grade) That is Related To Step 2 Study Treatment (CAB LA Plus VRC07-523LS)

  The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event OR premature discontinuation due to an adverse event (regardless of grade) that the clinical management committee judged to be at least possibly related to the CAB LA plus VRC07-523LS combination. Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017

  Measured from Step 2 entry through the remaining study follow-up (e.g., any time on Step 2 or Step 3 for a maximum follow-up time of 96 weeks).

• Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 44

  Virologic failure is defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL at or prior to Step 2 Week 44 of the CAB LA plus VRC07-523LS combination.

  Measured from Step 2 entry through Step 2 Week 44

Secondary Outcomes (13)

• Median Concentrations of VRC07-523LS

  Measured at Step 2 Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

• Median Concentration of CAB LA

  Measured at Step 2 Week 4, 8, 24, and 48

• ARV Resistance of Breakthrough Isolates

  Measured from Step 2 entry through Step 2 Week 48

• Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 24

  Measured from Step 2 entry through Step 2 Week 24

• Cumulative Probability of Confirmed Virologic Failure or Premature Treatment Discontinuation at or Prior to Step 2 Week 44

  Measured from Step 2 entry through Step 2 Week 44

Study Arms (1)

CAB LA + VRC07-523LS

EXPERIMENTAL

Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for up to 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44 (for a total of 12 injections). VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40 (for a total of 6 infusions). Step 3: Standard of Care (SOC) ART regimen for approximately 48 weeks.

Drug: Oral Cabotegravir (CAB); Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Long-Acting Injectable Cabotegravir (CAB LA); Biological: VRC07-523LS; Drug: Standard of Care (SOC) ART

Interventions

Oral Cabotegravir (CAB) DRUG

30 mg tablets administered orally

CAB LA + VRC07-523LS

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) DRUG

NRTIs were not provided by the study. Participants obtained NRTIs outside of the study through routine care.

CAB LA + VRC07-523LS

Long-Acting Injectable Cabotegravir (CAB LA) DRUG

600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection

CAB LA + VRC07-523LS

VRC07-523LS BIOLOGICAL

40 mg/kg administered as an intravenous (IV) infusion

Also known as: VRC-HIVMAB075-00-AB

CAB LA + VRC07-523LS

Standard of Care (SOC) ART DRUG

SOC ART was not provided by the study. Participants obtained SOC ART outside of the study through routine care.

CAB LA + VRC07-523LS

Eligibility Criteria

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

You may qualify if:

• Individual with HIV-1
• On a three-drug ART regimen for at least 8 weeks that includes a boosted protease inhibitor (PI), a nonnuceloside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (INSTI) plus two nuclesodie reverse transcriptase inhibitors (NRTI) with no history of switch due to virologic failure.
• CD4+ cell count greater than or equal to 350 cells/mm\^3
• Virally suppressed (\< 50 copies/mL) within 2 years prior to study entry
• Susceptibility to VRC07-523LS based on IC50 less than or equal to 0.25 ug/mL and a Maximum Percent Inhibition \> 98% using the Monogram PhenoSense Assay
• Certain laboratory values obtained within 60 days prior to study entry and in an acceptable range
• For participants of child-bearing potential:
• A negative serum or urine pregnancy test within 48 hours prior to study entry
• If participating in sexual activity that could lead to pregnancy, must agree to use an effective form of contraception.
• Negative HBsAg result
• Negative hepatitis C virus antibody
• Ability and willingness to provide written informed consent

You may not qualify if:

• Any previous receipt of humanized or human monoclonal antibody (licensed or investigational).
• Weight greater than 115 kg or less than 53 kg.
• AIDS-defining illness within 60 days prior to study entry.
• History of a severe allergic reaction within 2 years prior to study entry.
• Currently breastfeeding or pregnant.
• Active drug or alcohol use or dependence that would interfere with adherence to study requirements.
• Acute or serious illness that requires systemic treatment, quarantine, and/or hospitalization within 30 days prior to entry.
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry.
• Treatment for hepatitis C within 24 weeks prior to study entry.
• Vaccinations within 7 days prior to study entry.
• Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records).
• Personal or known family history of prolonged QT syndrome or a clinically significant finding on the screening electrocardiogram (ECG) based on an assessment of the screening ECG by that site investigator.
• Unstable liver disease or known biliary abnormalities
• Moderate or severe hepatic impairment (Class B or C) as determined by Child-Pugh classification.
• History of seizures or treatment for seizures within the past 2 years prior to study entry.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• ViiV Healthcare: collaborator

Study Sites (18)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10065, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (1)

• Kuritzkes DR. Broadly neutralizing antibodies and long-acting antiretroviral drugs as treatments for HIV. Curr Opin HIV AIDS. 2023 Jul 1;18(4):225-228. doi: 10.1097/COH.0000000000000801. Epub 2023 May 9.

  PMID: 37265259 DERIVED

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir; Standard of Care

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

This single-arm trial was conducted during the COVID-19 and Mpox public health emergencies, which prompted several countermeasures, including widespread use of multiple doses of new vaccines that can potentially impact virologic response.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

ACTG Network Coordinating Cent

Study Officials

• Babafemi Taiwo, MBBS

  Northwestern University CRS

  STUDY CHAIR

• Pablo Tebas, MD

  Hospital of the University of Pennsylvania CRS

  STUDY CHAIR

• Leah Burke, MD

  Weill Cornell Chelsea CRS

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 14, 2018
• Study Start: December 31, 2019
• Primary Completion: April 29, 2024
• Study Completion: April 29, 2024
• Last Updated: May 23, 2025
• Results First Posted: May 23, 2025

Record last verified: 2025-04

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 Advancing Clinical Therapeutics Globally (ACTG) by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. * For what types of analyses? * To achieve aims in the proposal approved by the ACTG. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the ACTG "Data Request" form at:https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Locations

US (17); PR (1)