Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection

• ClinicalTrials.gov Identifier: NCT04811040
• Recruitment Status: Active, not recruiting
• First Posted: March 23, 2021
• Last Update Posted: November 8, 2022
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: March 19, 2021
• First Posted Date: March 23, 2021
• Last Update Posted Date: November 8, 2022
• Actual Study Start Date: April 8, 2021
• Actual Primary Completion Date: June 9, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 19, 2021): Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: First dose date up to Week 26 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 4, 2022)

• Proportion 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 ]
• Proportion 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 ]
• Proportion of Participants With Positive Anti-Teropavimab Antibodies [ Time Frame: Week 26 ]
• Proportion of Participants With Positive Anti-zinlirvimab Antibodies [ Time Frame: Week 26 ]
• Change from Baseline in CD4+ Cell Count at Week 26 [ Time Frame: Baseline; Week 26 ]
• Proportion of Participants Who Develop Treatment-Emergent Resistance to Lenacapvir (LEN), Teropavimab, and Zinlirvimab [ Time Frame: Day 1 up to Week 26 ]
• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) [ Time Frame: First dose date up to Week 26 ]
• Pharmacokinetic (PK) Parameter: AUC0-t of Teropavimab, and Zinlirvimab, and LEN [ Time Frame: Day 1 up to Week 52 ]
  AUC0-t is defined as the concentration of drug over time from time zero to time "t".
• PK Parameter: AUClast of Teropavimab, and Zinlirvimab, and LEN [ Time Frame: Day 1 up to Week 52 ]
  AUClast is defined as the concentration of drug from time zero to the last observable concentration.
• PK Parameter: T1/2 of Teropavimab, and Zinlirvimab, and LEN [ Time Frame: Day 1 up to Week 52 ]
  T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
• PK Parameter: Cmax of Teropavimab, and Zinlirvimab, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Cmax is defined as the maximum observed concentration of drug.
• PK Parameter: Tmax of Teropavimab, and Zinlirvimab, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Tmax is defined as the time (observed time point) of Cmax.
• PK Parameter: Tlast of Teropavimab, and Zinlirvimab, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
• PK Parameter: Ct of Teropavimab, and Zinlirvimab, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Ct is the concentration at a particular time (t).

Original Secondary Outcome Measures (submitted: March 19, 2021)

• Proportion 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 ]
• Proportion 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 ]
• Proportion 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 ]
• Proportion 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 ]
• Proportion of Participants With Positive Anti-GS-5423 Antibodies [ Time Frame: Day 1 up to Week 52 ]
• Proportion of Participants With Positive Anti-GS-2872 Antibodies [ Time Frame: Day 1 up to Week 52 ]
• Change from Baseline in CD4+ Cell Count at Week 26 [ Time Frame: Baseline; Week 26 ]
• Change from Baseline in CD4+ Cell Count at Week 52 [ Time Frame: Baseline; Week 52 ]
• Proportion of Participants Who Develop Resistance to Lenacapvir (LEN), GS-5423, and GS-2872 [ Time Frame: Day 1 up to Week 52 ]
• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) [ Time Frame: First dose date up to Week 52 ]
• Pharmacokinetic (PK) Parameter: AUC0-t of GS-5423, and GS-2872, and LEN [ Time Frame: Day 1 up to Week 52 ]
  AUC0-t is defined as the concentration of drug over time from time zero to time "t".
• PK Parameter: AUClast of GS-5423, and GS-2872, and LEN [ Time Frame: Day 1 up to Week 52 ]
  AUClast is defined as the concentration of drug from time zero to the last observable concentration.
• PK Parameter: T1/2 of GS-5423, and GS-2872, and LEN [ Time Frame: Day 1 up to Week 52 ]
  T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
• PK Parameter: Cmax of GS-5423, and GS-2872, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Cmax is defined as the maximum observed concentration of drug.
• PK Parameter: Tmax of GS-5423, and GS-2872, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Tmax is defined as the time (observed time point) of Cmax.
• PK Parameter: Tlast of GS-5423, and GS-2872, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
• PK Parameter: Ct of GS-5423, and GS-2872, and LEN [ Time Frame: Day 1 up to Week 52 ]
  Ct is the concentration at a particular time (t).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection
• Official Title: A Phase 1b Randomized, Blinded, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection
• Brief Summary: The primary objective of this study is to evaluate the safety and tolerability of a combination of the broadly neutralizing antibodies (bNAbs) teropavimab (formerly GS-5423) and zinlirvimab (formerly GS-2872) in combination with the HIV capsid inhibitor lenacapavir (LEN).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Clinical pharmacologist and sponsor are not masked to treatment assignment.

Primary Purpose: Treatment

• Condition: HIV-1 Infection

Intervention

• Drug: Oral Lenacapavir
  Tablets administered without regard to food
  Other Name: GS-6207
• Drug: Subcutaneous Lenacapavir
  Administered in the abdomen via subcutaneous injections
  Other Name: GS-6207
• Biological: Teropavimab
  Administered intravenously
  Other Names:

  • 3BNC117-LS
  • GS-5423
• Biological: Zinlirvimab
  Administered intravenously
  Other Names:

  • 10-1074-LS
  • GS-2872

Study Arms

• Experimental: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C
  Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: Subcutaneous Lenacapavir
  • Biological: Teropavimab
  • Biological: Zinlirvimab
• Experimental: LEN, Teropavimab, Zinlirvimab Dose D
  Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: Subcutaneous Lenacapavir
  • Biological: Teropavimab
  • Biological: Zinlirvimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 4, 2022): 32
• Original Estimated Enrollment (submitted: March 19, 2021): 50
• Estimated Study Completion Date: December 2023
• Actual Primary Completion Date: June 9, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• On first-line antiretroviral therapy (ART) for ≥ 2 years prior to screening. A change in ART regimen ≥ 28 days prior to screening for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed
• No documented historical resistance to the current ART regimen
• Plasma HIV-1 RNA < 50 copies/mL at screening
• Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 18 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable.

• Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening by the PhenoSense mAb Assay (Monogram Biosciences) for inclusion in the Primary Cohort; sensitivity at screening by the PhenoSense mAb Assay (Monogram Biosciences) to 1 mAb, either teropavimab or zinlirvimab, within 18 months prior to enrollment for inclusion in the optional Pilot Cohort

  -- In both cohorts, teropavimab sensitivity is defined as 90% inhibitory concentration (IC90) ≤ 2 μg/mL; zinlirvimab sensitivity is defined as IC90 ≤ 2 μg/mL;

• CD4+ count nadir ≥ 350 cells/μL
• Screening CD4+ count ≥ 500 cells/μL
• Availability of a fully active alternative ART regimen, in the opinion of the investigator, in the event of discontinuation of the current ART regimen with development of resistance

Key Exclusion Criteria:

• Comorbid condition requiring ongoing immunosuppression
• Evidence of current hepatitis B virus (HBV) infection
• Evidence of current hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
• History of opportunistic infection or illness indicative of Stage 3 HIV disease

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04811040
• Other Study ID Numbers: GS-US-536-5816
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: June 2022