NCT07682961

Brief Summary

The goal of this clinical study is to compare how effective a long-acting injectable treatment of lenacapavir (LEN), teropavimab (TAB), and zinlirvimab (ZAB) versus (CAB) and rilpivirine (RPV) injections given every 8 weeks in adults with HIV-1 whose virus is well controlled on daily oral treatment, after 1 year (52 weeks) of the treatment. The primary objective of this study are to evaluate the efficacy of switching to the regimen of LEN, TAB, and ZAB versus switching to CAB and RPV in virologically suppressed people with HIV-1 (PWH) as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
590

participants targeted

Target at P50-P75 for phase_3 hiv-infections

Timeline
80mo left

Started Jul 2026

Longer than P75 for phase_3 hiv-infections

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress1%
Jul 2026Mar 2033

First Submitted

Initial submission to the registry

June 26, 2026

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 6, 2026

Completed
8 days until next milestone

Study Start

First participant enrolled

July 14, 2026

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2029

Expected
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2033

Last Updated

July 22, 2026

Status Verified

July 1, 2026

Enrollment Period

2.6 years

First QC Date

June 26, 2026

Last Update Submit

July 20, 2026

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

  • Proportion of Participants With HIV-1 ribonucleic acid (RNA) ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm.

    Week 52

Secondary Outcomes (12)

  • Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 92 as Defined by the US FDA Snapshot Algorithm.

    Week 92

  • Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm

    Week 52

  • Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 92 as Determined by the US FDA Snapshot Algorithm.

    Week 92

  • Change From Baseline in clusters of differentiation 4 (CD4) (CD4)+ T-cell Counts at Week 52

    Baseline, Week 52

  • Change From Baseline in CD4+ T-cell Counts at Week 92

    Baseline, Week 92

  • +7 more secondary outcomes

Study Arms (2)

Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)

EXPERIMENTAL

Participants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92. After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.

Drug: LenacapavirDrug: Lenacapavir TabletDrug: TeropavimabDrug: Zinlirvimab

Treatment Group 2: Cabotegravir (CAB) + Rilpivirine (RPV)

ACTIVE COMPARATOR

Participants will discontinue their baseline oral antiretroviral therapy (ART) and will receive intramuscular (IM) CAB 600 mg + RPV 900 mg on Day 1, Week 4 and then every 8 weeks for up to 92 weeks. After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discounting the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.

Drug: CabotegravirDrug: Rilpivirine

Interventions

LenacapavirDRUG

Administered subcutaneously

Also known as: LEN
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
Lenacapavir TabletDRUG

Administered orally

Also known as: LEN
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
TeropavimabDRUG

Administered intravenously (IV)

Also known as: TAB, GS-5423
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
ZinlirvimabDRUG

Administered IV

Also known as: ZAB, GS-2872
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
CabotegravirDRUG

Administered intramuscular (IM)

Also known as: CAB
Treatment Group 2: Cabotegravir (CAB) + Rilpivirine (RPV)
RilpivirineDRUG

Administered IM

Also known as: RPV
Treatment Group 2: Cabotegravir (CAB) + Rilpivirine (RPV)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria:
  • \) Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening.
  • At least 1 documented HIV-1 RNA level measured between 6 months and 12 months (+2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). A single virologic elevation of ≥ 50 copies/mL and \< 400 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable if the subsequent plasma HIV-1 RNA level is \< 50 copies/mL.
  • A plasma HIV-1 RNA test \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) within the last 6 months prior to screening.
  • \) If \> 1 plasma HIV-1 RNA measurements in the last 6 months prior to screening are available, all must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
  • On a stable oral ARV therapy (ART) for ≥ 6 months prior to screening.
  • A change in ART regimen ≥ 3 months prior to the screening visit for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed; individuals with a change in ART regimen ≥ 3 months prior to screening must have been on the regimen for ≥ 3 months prior to screening, and all HIV-1 RNA measurements in that period must be \< 50 copies/mL. There are no permitted changes to ART regimens between screening and Day 1.

You may not qualify if:

  • History of an opportunistic infection or illness indicative of Stage 3 HIV disease.
  • History of treatment failure.
  • Known or suspected resistance to either CAB or RPV.
  • Resistance to CAB defined as the following mutations: G118R, Q148K, Q148R, T66K+L74M, E92Q+N155H, E138A+Q148R, E138K+Q148K/R, G140C+Q148R, G140S+Q148H/K/R, Y143H+N155H, and Q148R+N155H.
  • Resistance to RPV defined as the following mutations: K101E and P; E138A, G, K, R, and Q; V179L; Y181C, I, and V; Y188L; H221Y; F227C; M230I and L, and the combination of L100I/K103N.
  • Individuals with a dermatologic condition or implanted prothesis overlying the gluteal injection site for CAB + RPV.
  • Known hypersensitivity to the study intervention, its metabolites, or formulation excipients.
  • Active, serious infections (other than HIV-1) requiring therapy \< 30 days prior to randomization.
  • Active tuberculosis infection.
  • Acute hepatitis of any cause \< 30 days before randomization.
  • History of, or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or severe hepatic impairment (Child-Pugh Class C).
  • Active malignancy requiring acute systemic therapy.
  • Have poor venous access that would limit phlebotomy or intravenous (IV) infusion of study drugs.
  • Prior use of, or exposure to, LEN or a broadly neutralizing antibody (bNAb) for HIV-1.
  • Prior use of, or exposure to, long-acting (LA) injectable CAB or LA injectable RPV.
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

CAN Community Health Fort Lauderdale

Fort Lauderdale, Florida, 33316, United States

RECRUITING

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

RECRUITING

Be Well Medical Center

Berkley, Michigan, 48072, United States

RECRUITING

Related Links

MeSH Terms

Conditions

HIV Infections

Interventions

lenacapavircabotegravirRilpivirine

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

NitrilesOrganic ChemicalsPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

1-833-445-3230 (GILEAD-0)GileadClinicalTrials@gilead.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 26, 2026

First Posted

July 6, 2026

Study Start

July 14, 2026

Primary Completion (Estimated)

March 1, 2029

Study Completion (Estimated)

March 1, 2033

Last Updated

July 22, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will not share

Locations

US(3)