Study to Assess the Effectiveness and Safety of Lenacapavir for Human Immunodeficiency Virus (HIV) Pre-Exposure Prophylaxis (PURPOSE 2)

• ClinicalTrials.gov Identifier: NCT04925752
• Recruitment Status: Recruiting
• First Posted: June 14, 2021
• Last Update Posted: July 26, 2022
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: May 28, 2021
• First Posted Date: June 14, 2021
• Last Update Posted Date: July 26, 2022
• Actual Study Start Date: June 28, 2021
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 23, 2022)

• Incidence Phase: Background HIV Incidence Reported Per 100-Person-Years (PY) [ Time Frame: At Screening ]
• Randomized Phase: Background HIV Incidence Reported Per 100-PY of Follow-up [ Time Frame: When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]

Original Primary Outcome Measures (submitted: June 11, 2021)

• Incidence Phase: Background HIV Incidence Reported Per 100-Person-Years (PY) [ Time Frame: At Screening ]
• Randomized Phase: Background HIV Incidence Reported Per 100-PY of Follow-up [ Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]

Current Secondary Outcome Measures (submitted: February 23, 2022)

• HIV Incidence Among Participants While Adherent to Study Drug [ Time Frame: When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]
• Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]
• Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities [ Time Frame: When all participants have completed a minimum of 52 weeks of follow-up in the study, or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]

Original Secondary Outcome Measures (submitted: June 11, 2021)

• HIV Incidence Among Participants While Adherent to Study Drug [ Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]
• Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]
• Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities [ Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 130 weeks) ]

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

Descriptive Information

• Brief Title: Study to Assess the Effectiveness and Safety of Lenacapavir for Human Immunodeficiency Virus (HIV) Pre-Exposure Prophylaxis
• Official Title: A Phase 3, Double-Blind, Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Subcutaneous Twice Yearly Long-Acting Lenacapavir for HIV Pre-Exposure Prophylaxis in Cisgender Men, Transgender Women, Transgender Men, and Gender Nonbinary People ≥ 16 Years of Age Who Have Sex With Male Partners and Are at Risk for HIV Infection

Brief Summary

The primary objective of this study is to evaluate the efficacy of lenacapavir (LEN) in preventing the risk of human immunodeficiency virus (HIV) - 1 infection relative to the background HIV-1 incidence rate.

The study will be conducted in 2 parts: a cross-sectional study (Incidence Phase) and a double-blind, randomized study (Randomized Phase). The Incidence Phase will include initial assessments that will provide an estimate of the concurrent background HIV-1 incidence rate. The Randomized Phase of the study will have a Blinded Phase, a LEN Open-label Extension (OLE) Phase, and a pharmacokinetic (PK) Tail Phase.

The primary objective for the Incidence Phase of this study is to estimate the HIV-1 background incidence rate. The primary objective of the Randomized Blinded Phase of this study is to evaluate the efficacy of lenacapavir for HIV-1 pre-exposure prophylaxis (PrEP) in cisgender men (CGM), transgender women (TGW), transgender men (TGM), and gender nonbinary people (GNB) ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV-1 infection.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Pre-Exposure Prophylaxis of HIV Infection

Intervention

• Drug: Oral Lenacapavir (LEN)
  Tablets administered orally without regard to food
  Other Name: GS-6207
• Drug: F/TDF
  Tablets administered orally
  Other Name: Truvada®
• Drug: Sub-cutaneous (SC) Lenacapavir (LEN)
  Administered via SC injections
  Other Name: GS-6207
• Drug: Placebo SC LEN
  Administered via SC injections
• Drug: PTM F/TDF
  Tablets administered orally
• Drug: PTM Oral LEN
  Tablets administered orally
• Drug: F/TAF (for US participants only)
  F/TAF tablets administered orally once daily

Study Arms

• Experimental: Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF

  Participants will receive the following for at least 52 weeks:

  • Subcutaneous (SC) lenacapavir (LEN) 927 mg every 26 weeks
  • Oral PTM Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) once daily
  • Oral LEN 600 mg on Days 1 and 2

  Participants will receive oral LEN if SC injections are not available

  Interventions:

  • Drug: Oral Lenacapavir (LEN)
  • Drug: Sub-cutaneous (SC) Lenacapavir (LEN)
  • Drug: PTM F/TDF
• Experimental: Blinded Phase: Placebo LEN + F/TDF

  Participants will receive the following for at least 52 weeks:

  • SC LEN placebo every 26 weeks
  • Oral F/TDF 200/300 mg once daily
  • PTM Oral LEN on Days 1 and 2

  Participants will receive oral LEN placebo if SC injections are not available

  Interventions:

  • Drug: F/TDF
  • Drug: Placebo SC LEN
  • Drug: PTM Oral LEN
• Experimental: LEN Open-Label Extension (OLE) Phase

  After completion of the Blinded phase, participants will be offered entry into the LEN OLE Phase.

  Participants randomized to LEN will continue to receive SC LEN 927 mg every 26 weeks for a total of 2 doses.

  Participants randomized to F/TDF will receive SC LEN 927 mg on OLE Day 1, OLE Week 26, and will also receive oral LEN 600 mg on OLE Days 1 and 2.

  Interventions:

  • Drug: Oral Lenacapavir (LEN)
  • Drug: Sub-cutaneous (SC) Lenacapavir (LEN)
• Experimental: PK Tail Phase

  At the completion of the LEN OLE phase, participants will transition into the PK Tail phase.

  Additionally, participants that prematurely discontinue the study drug during blinded phase and participants that were randomized to LEN who choose not to continue in the LEN OLE Phase are also eligible to transition to the PK Tail Phase.

  Participants will receive oral F/TDF (or Emtricitabine/Tenofovir Alafenamide (F/TAF) for US participants only) once daily for 78 weeks beginning 26 weeks after the last injection of LEN.

  Interventions:

  • Drug: F/TDF
  • Drug: F/TAF (for US participants only)

• Publications *: Cespedes M, Das M, Hojilla JC, Blumenthal J, Mounzer K, Ramgopal M, Hodge T, Torres TS, Peterson C, Shibase S, Elliott A, Demidont AC, Callaghan L, Watson CC, Carter C, Kintu A, Baeten JM, Ogbuagu O. Proactive strategies to optimize engagement of Black, Hispanic/Latinx, transgender, and nonbinary individuals in a trial of a novel agent for HIV pre-exposure prophylaxis (PrEP). PLoS One. 2022 Jun 3;17(6):e0267780. doi: 10.1371/journal.pone.0267780. eCollection 2022.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 11, 2021): 3000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2027
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

Incidence Phase

• CGM, TGW, TGM, and GNB who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV infection.
• HIV-1 status unknown at screening and no prior HIV-1 testing within the last 3 months

• Sexually active with ≥ 1 partner assigned male at birth (condomless receptive anal sex) in the last 12 months and 1 of the following:

  • Condomless receptive anal sex with ≥ 2 partners in the last 12 weeks
  • History of syphilis, rectal gonorrhea, or rectal chlamydia in the last 24 weeks
  • Self-reported use of stimulants with sex in the last 12 weeks

Randomized Phase

• Negative local rapid fourth generation HIV-1/2 Ab/Ag, central fourth generation HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT)
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr)

Key Exclusion Criteria:

Incidence Phase

• Prior use of oral PrEP (including F/TDF or F/TAF) in the past 12 weeks or any prior use of long-acting systemic PrEP (including cabotegravir or islatravir)
• Prior recipient of an HIV vaccine or HIV broadly neutralizing antibody formulation

Randomized Phase

• Acute viral hepatitis A, B or C or evidence of chronic hepatitis B or C infection
• Severe hepatic impairment or a history of or current clinical decompensated liver cirrhosis

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

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Cisgender male, Transgender male, Transgender female, and Gender non-binary

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

• Listed Location Countries: Puerto Rico, South Africa, United States

Administrative Information

• NCT Number: NCT04925752
• Other Study ID Numbers: GS-US-528-9023; DOH-27-102021-6681 ( Other Identifier: South African National Clinical Trial Registry )
• Has Data Monitoring Committee: Yes

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: July 2022