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NCT Number: NCT06544733

Study of Oral Weekly Lepetegravir (Formerly GS-1720) and Lenacapavir Pacfosacil (Formerly GS-4182) Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed

The goal of this clinical study is to learn more about the experimental drugs lepetegravir and lenacapavir pacfosacil; to compare the combination of lepetegravir and lenacapavir pacfosacil with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), to see if the combination of lepetegravir and lenacapavir pacfosacil is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection.

This study has two phases: Phase 2 and Phase 3.

The primary objectives of this study are:

Phase 2: To evaluate the efficacy of switching to oral weekly lepetegravir in combination with lenacapavir pacfosacil versus continuing BVY in virologically suppressed people with HIV-1 (PWH) at Week 24.

Phase 3: To evaluate the efficacy of switching to oral weekly lepetegravir /lenacapavir pacfosacil Fixed-dose combination (FDC) tablet regimen versus continuing BVY in virologically suppressed PWH at Week 48.

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 and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Centro Ararat, Inc., San Juan, PR, Puerto Rico

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 24 weeks before and at screening.
  • Receiving BVY for ≥ 24 weeks prior to screening.

Key Exclusion Criteria:

  • Prior use of, or exposure to LEN, lepetegravir, or lenacapavir pacfosacil.
  • History of virologic failure while on an integrase strand-transfer inhibitor (INSTI)-based regimen.
  • Documented integrase strand-transfer inhibitor (INSTI) resistance, specifically, resistance-associated mutations (RAMs) E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.
  • Prior use of any long-acting (LA) parenteral antiretrovirals (ARV) such as monoclonal antibodies (mAbs) or broadly neutralizing antibodies (bNAbs) targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine.
  • Any of the following laboratory values at screening:
  • Clusters of differentiation 4 (CD4) cell count < 200 cells/mm^3 at screening
  • Glomerular filtration rate < 60 mL/min according to the Modification of Diet in Renal Disease formula
  • Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN)
  • Direct bilirubin > 1.5 × ULN
  • Platelets count < 50,000 cells/mm^3
  • Hemoglobin < 8.0 g/dL
  • Active or occult hepatitis B virus (HBV) infection.
  • Active hepatitis C virus (HCV).

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

Treatment and study plan

Lepetegravir

Drug

Tablets administered orally without regard to food

Other names: GS-1720

Lenacapavir pacfosacil

Drug

Tablets administered orally without regard to food

Other names: GS-4182

Placebo to Match BVY

Drug

Tablets administered orally without regard to food

bictegravir/emtricitabine/tenofovir alafenamide

Drug

Tablets administered orally without regard to food

Other names: Biktarvy®

Lepetegravir/Lenacapavir pacfosacil FDC

Drug

Tablets administered orally without regard to food

Other names: GS-1720/GS-4182 FDC

Placebo to Match GS1720/GS-4182 FDC

Drug

Tablets administered orally without regard to food

Primary outcomes

  1. Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm

    Time frame: Week 24

  2. Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 48

Secondary outcomes

  1. Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 12

  2. Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 48

  3. Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 12

  4. Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 24

  5. Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 48

  6. Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4+) T-cell Count at Week 12

    Time frame: Baseline, Week 12

  7. Phase 2: Change From Baseline in CD4+ T-cell Count at Week 24

    Time frame: Baseline, Week 24

  8. Phase 2: Change From Baseline in CD4+ T-cell Count at Week 48

    Time frame: Baseline, Week 48

  9. Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Through Week 12

    Time frame: First dose date up to Week 12

  10. Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24

    Time frame: First dose date up to Week 24

  11. Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48

    Time frame: First dose date up to Week 48

  12. Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12

    Time frame: First dose date up to Week 12

  13. Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 24

    Time frame: First dose date up to Week 24

  14. Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48

    Time frame: First dose date up to Week 48

  15. Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Lepetegravir and Lenacapavir (LEN)

    Time frame: Day 1 up to Week 48

    Cmax is defined as the maximum observed concentration of drug.

  16. Phase 2: PK Parameter: Tmax of Lepetegravir and LEN

    Time frame: Day 1 up to Week 48

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

  17. Phase 2: PK Parameter: Ctau of Lepetegravir and LEN

    Time frame: Day 1 up to Week 48

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  18. Phase 2: PK Parameter: AUCtau of Lepetegravir and LEN

    Time frame: Day 1 up to Week 48

    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  19. Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 96

  20. Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 48

  21. Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: Week 96

  22. Phase 3: Change From Baseline in CD4+ T-cell Count at Week 48

    Time frame: Baseline, Week 48

  23. Phase 3: Change From Baseline in CD4+ T-cell Count at Week 96

    Time frame: Baseline, Week 96

  24. Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48

    Time frame: First dose date up to Week 48

  25. Phase 3: Proportion of Participants Experiencing TEAEs Through Week 96

    Time frame: First dose date up to Week 96

  26. Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48

    Time frame: First dose date up to Week 48

  27. Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96

    Time frame: First dose date up to Week 96

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study title

An Operationally Seamless Phase 2/3, Randomized, Active-Controlled Study Evaluating the Safety and Efficacy of an Oral Weekly Regimen of GS-1720 in Combination With GS-4182 Versus Biktarvy in Virologically Suppressed People With HIV-1

Acronym: WONDERS1

Important dates

Study start
2024
Primary completion
2028
Study completion
2029
First posted
Aug 9, 2024
Registry last updated
Apr 17, 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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