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NCT Number: NCT05729568

A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (TAB; GS-5423) and zinlirvimab (ZAB; GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection.

The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

HIV-1 Infection

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

East Sydney Doctors, Darlinghurst, New South Wales, Australia

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About this study

Participants will be randomized in Treatment Groups 1 and 2 to receive LEN, TAB, and ZAB, with differing doses of TAB and ZAB between the 2 groups and in Treatment Group 3 to continue their baseline oral ART for 52 weeks. Eligible participants in Treatment Groups 1 through 3 will have the option of participating in the study extension phase to receive LEN, TAB and ZAB after completing study follow-up through Week 52.

Treatment Group 2 was removed prior to dosing of all groups during Protocol Amendment 2.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
  • No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
  • Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) < 50 copies/mL at screening visit 2.
  • Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
  • Proviral phenotypic sensitivity to both teropavimab and zinlirvimab by the PhenoSense Assay (Monogram Biosciences).
  • Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.

Key Exclusion Criteria:

  • Comorbid condition requiring ongoing immunosuppression.
  • Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.
  • Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2.
  • History of opportunistic infection or illness indicative of Stage 3 HIV disease.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

Teropavimab

Drug

Administered intravenously

Other names: GS-5423, 3BNC117-LS

Zinlirvimab

Drug

Administered intravenously

Other names: GS-2872, 10-1074-LS

Lenacapavir Tablet

Drug

Administered orally

Other names: GS-6207

Lenacapavir Injection

Drug

Administered subcutaneously

Other names: GS-6207, Sunlenca®

Antiretroviral therapy

Drug

Antiretroviral therapy, administered orally may include regimens such as: bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide.

Primary outcomes

  1. Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 Copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm

    Time frame: Week 26

    Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; or b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to adverse event (AE) or death and had last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL.

    Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.

Secondary outcomes

  1. Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 52

    Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 52 analysis window; or b) who did not have on-treatment HIV-1 RNA data in the Week 52 analysis window and i) discontinued study drug prior to or in the Week 52 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 52 analysis window due to adverse event (AE) or death and had last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 52 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL.

    Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.

  2. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 26

    Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 26 was analyzed using the US FDA-defined snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA < 50 copies/mL in the Week 26 analysis window.

    The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.

  3. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 52

    Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 52 was analyzed using the US FDA-defined snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA < 50 copies/mL in the Week 52 analysis window. The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.

  4. Change From Baseline in Clusters of Differentiation 4 (CD4) + T-cell Counts at Week 26

    Time frame: Baseline, Week 26

  5. Change From Baseline in CD4+ T-cell Counts at Week 52

    Time frame: Baseline, Week 52

  6. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

    Time frame: Up to approximately 6 years

  7. Trough Concentration at Week 26 Predose for TAB and ZAB

    Time frame: Week 26 predose

    Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

  8. Trough Concentration at Week 26 Predose for LEN

    Time frame: Week 26 predose

    Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

  9. Trough Concentration at Week 52 Predose for TAB and ZAB

    Time frame: Week 52 predose

    Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

  10. Trough Concentration at Week 52 Predose for LEN

    Time frame: Week 52 predose

    Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

  11. Pharmacokinetic (PK) Parameter: AUC0-tau for TAB and ZAB

    Time frame: Up to approximately 6 years

    AUC0-tau is defined as the partial area under the concentration versus time curve from time "0" to time "t".

  12. PK Parameter: t1/2 for TAB and ZAB

    Time frame: Up to approximately 6 years

    t1/2 is defined as the terminal elimination half-life.

  13. PK Parameter: Cmax for TAB and ZAB

    Time frame: Up to approximately 6 years

    Cmax is defined as the maximum observed concentration of drug.

  14. PK Parameter: Cmax for LEN

    Time frame: Up to approximately 6 years

    Cmax is defined as the maximum observed concentration of drug.

  15. PK Parameter: Tmax for TAB, ZAB, and LEN

    Time frame: Up to approximately 6 years

    Tmax is defined as the time (observed time point) of Cmax.

  16. Percentage of Participants With Treatment-emergent Anti-TAB and Anti-ZAB Antibodies

    Time frame: Up to approximately 6 years

    Anti-TAB and anti-ZAB antibodies incidence referred to the percentage of participants who have treatment-emergent anti-TAB and anti-ZAB antibodies among all participants evaluable for anti-drug antibody (ADA) incidence.

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study title

A Phase 2 Randomized, Open-label Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With the Capsid Inhibitor Lenacapavir as Long-Acting Treatment Dosed Every 6 Months in Virologically Suppressed Adults With HIV-1 Infection

Important dates

Study start
2023
Primary completion
2024
Study completion
2030
First posted
Feb 15, 2023
Registry last updated
Apr 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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