Study to Evaluate the Safety and Efficacy of Lenacapavir in Combination With Other Antiretroviral Agents in People Living With HIV (CALIBRATE)

• ClinicalTrials.gov Identifier: NCT04143594
• Recruitment Status: Completed
• First Posted: October 29, 2019
• Results First Posted: December 19, 2022
• Last Update Posted: October 10, 2023
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: October 28, 2019
• First Posted Date: October 29, 2019
• Results First Submitted Date: September 29, 2022
• Results First Posted Date: December 19, 2022
• Last Update Posted Date: October 10, 2023
• Actual Study Start Date: November 22, 2019
• Actual Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2022)

Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm [ Time Frame: Week 54 ]

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 54 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 54 window was between Day 323 and 413 (inclusive).

• Original Primary Outcome Measures (submitted: October 28, 2019): Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Week 54 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 54 ]

Current Secondary Outcome Measures (submitted: November 22, 2022)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 28 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 28 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 28 window was between Days 176 and 231 (inclusive).
• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 38 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 38 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Days 232 and 322 (inclusive).
• Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 80 ]
• Change From Baseline in Log10 HIV-1 RNA at Week 28 [ Time Frame: Baseline; Week 28 ]
• Change From Baseline in Log10 HIV-1 RNA at Week 38 [ Time Frame: Baseline; Week 38 ]
• Change From Baseline in Log10 HIV-1 RNA at Week 54 [ Time Frame: Baseline; Week 54 ]
• Change From Baseline in Log10 HIV-1 RNA at Week 80 [ Time Frame: Baseline; Week 80 ]
• Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 28 [ Time Frame: Baseline; Week 28 ]
• Change From Baseline in CD4+ Cell Count at Week 38 [ Time Frame: Baseline; Week 38 ]
• Change From Baseline in CD4+ Cell Count at Week 54 [ Time Frame: Baseline; Week 54 ]
• Change From Baseline in CD4+ Cell Count at Week 80 [ Time Frame: Baseline; Week 80 ]
• Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to 54 weeks ]
  TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug.
• Percentage of Participants Who Experienced Laboratory Abnormalities [ Time Frame: First dose date up to 54 weeks ]
  Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline visit, up to last exposure date for participants who permanently discontinued study drug, or the last available date in the database snapshot for participants who were still on treatment at the time of an interim analysis. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening.
• Pharmacokinetics (PK) of TAF (Tenofovir Alafenamide)and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 ]
  AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2) and at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.
• PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 ]
  Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.
• PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 ]
  Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.
• PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 ]
  Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK sub study analysis was conducted for Group 1 and 2 on Day 1.
• PK of TAF and TFV: AUClast at Weeks 16, 22, or 28 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
• PK of TAF and TFV: Cmax at Weeks 16, 22, or 28 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
• PK of TAF and TFV: Tmax at Weeks 16, 22, or 28 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
• PK of TFV: Clast at Weeks 16, 22, or 28 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TFV was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
• PK of TAF: AUClast at Week 38 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.
• PK of TAF: Cmax at Week 38 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.
• PK of TAF: Tmax at Week 38 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.
• PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22 [ Time Frame: 0 hours (Predose) and at 1, 2, and 6 hours postdose ]
  AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A peripheral blood mononuclear cell (PBMC) substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
• PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22 [ Time Frame: 0 hours (Predose) and at 1, 2, and 6 hours postdose ]
  Cmax is defined as the maximum observed concentration of drug. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
• PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22 [ Time Frame: 0 hours (Predose) and at 1, 2, and 6 hours postdose ]
  Tmax is defined as the time (observed time point) of Cmax. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.
• PK of Bictegravir (BIC): AUClast at Week 38 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.
• PK of BIC: Cmax at Week 38 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.
• PK of BIC: Tmax at Week 38 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.
• PK of BIC: Clast at Week 38 [ Time Frame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose ]
  Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2.

Original Secondary Outcome Measures (submitted: October 28, 2019)

• Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 28 ]
• Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 38 ]
• Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 80 ]
• Change from Baseline in Log10 HIV-1 RNA at Week 28 [ Time Frame: Baseline; Week 28 ]
• Change from Baseline in Log10 HIV-1 RNA at Week 38 [ Time Frame: Baseline; Week 38 ]
• Change from Baseline in Log10 HIV-1 RNA at Week 54 [ Time Frame: Baseline; Week 54 ]
• Change from Baseline in Log10 HIV-1 RNA at Week 80 [ Time Frame: Baseline; Week 80 ]
• Change from Baseline in CD4+ Cell Count at Week 28 [ Time Frame: Baseline; Week 28 ]
• Change from Baseline in CD4+ Cell Count at Week 38 [ Time Frame: Baseline; Week 38 ]
• Change from Baseline in CD4+ Cell Count at Week 54 [ Time Frame: Baseline; Week 54 ]
• Change from Baseline in CD4+ Cell Count at Week 80 [ Time Frame: Baseline; Week 80 ]

• 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 Lenacapavir in Combination With Other Antiretroviral Agents in People Living With HIV
• Official Title: A Phase 2 Randomized, Open Label, Active Controlled Study Evaluating the Safety and Efficacy of Long-acting Capsid Inhibitor GS-6207 in Combination With Other Antiretroviral Agents in People Living With HIV
• Brief Summary: The primary objective of this study is to evaluate the efficacy of lenacapavir (formerly GS-6207) containing regimens in people living with human immunodeficiency virus (HIV) (PLWH).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1-infection

Intervention

• Drug: Oral Lenacapavir
  Tablets administered without regard to food
  Other Name: GS-6207
• Drug: F/TAF
  Tablets administered without regard to food
  Other Name: Descovy®
• Drug: Subcutaneous Lenacapavir
  Administered in the abdomen via subcutaneous injections
  Other Name: GS-6207
• Drug: TAF
  Tablets administered without regard to food
• Drug: BIC
  Tablets administered without regard to food
• Drug: B/F/TAF
  Tablets administered without regard to food
  Other Name: Biktarvy®

Study Arms

• Experimental: Lenacapavir, F/TAF, and TAF

  Induction: Participants will receive oral lenacapavir 600 mg, 600 mg, and 300 mg at Days 1, 2, and 8, respectively. Participants will also begin oral daily emtricitabine/tenofovir alafenamide (F/TAF) 200/25mg from Day 1 onwards for a total of 28 weeks. On Day 15 participants will receive subcutaneous (SC) lenacapavir 927 mg.

  Maintenance: Participants will receive SC lenacapavir 927 mg at Week 28 and every 26 weeks. Participants will discontinue oral daily F/TAF 200/25 mg at Week 28 and begin taking oral daily TAF 25 mg.

  May require oral weekly bridging if an SC injection of GS-6207 cannot be administered for any reason within the protocol visit window.

  Participants willing to continue the study beyond Week 80 will continue to receive SC lenacapavir 927 mg every 6 months (26 weeks) and oral daily TAF 25 mg from Week 80 onwards.

  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: F/TAF
  • Drug: Subcutaneous Lenacapavir
  • Drug: TAF
• Experimental: Lenacapavir, F/TAF, and BIC

  Induction: Participants will receive oral lenacapavir 600 mg, 600 mg, and 300 mg at Days 1, 2, and 8, respectively. Participants will also begin oral daily F/TAF 200/25 mg from Day 1 onward for a total of 28 weeks. On Day 15 participants will receive SC lenacapavir 927 mg.

  Maintenance: Participants will receive SC lenacapavir 927 mg at Week 28 and every 26 weeks. Participants will discontinue oral daily F/TAF 200/25 mg at Week 28 and begin oral daily bictegravir (BIC) 75 mg.

  May require oral weekly bridging if an SC injection of GS-6207 cannot be administered for any reason within the protocol visit window.

  Participants willing to continue the study beyond Week 80 will continue to receive SC lenacapavir 927 mg every 6 months (26 weeks) and oral daily bictegravir (BIC) 75 mg from Week 80 onwards.

  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: F/TAF
  • Drug: Subcutaneous Lenacapavir
  • Drug: BIC
• Experimental: Lenacapavir and F/TAF

  Participants will receive oral lenacapavir 600 mg at Day 1 and Day 2. On Day 3, participants will begin oral daily lenacapavir 50 mg. Participants will begin oral daily F/TAF 200/25 mg from Day 1 onwards.

  Participants willing to continue the study beyond Week 80 will continue to receive oral daily lenacapavir 50 mg and oral daily F/TAF 200/25 mg from Week 80 onwards.

  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: F/TAF
• Active Comparator: B/F/TAF
  Participants will receive oral daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg at Day 1 and throughout their participation in the study.
  Intervention: Drug: B/F/TAF

Publications *

• Gupta SK, Berhe M, Crofoot G, et al. Long-Acting Subcutaneous Lenacapavir Dosed Every 6 Months as part of a Combination Regimen in Treatment-Naïve People with HIV: Interim 16-week Results of a Randomized, Open-label, Phase 2 Induction-Maintenance Study (CALIBRATE)
• VanderVeen, L, Margot N, Naik V, et al. Interim Resistance Analysis of Long-Acting Lenacapavir in Treatment-Naïve People with HIV at 28 Weeks (CALIBRATE)
• Harris P, Henderson R, Hayward P. Highlights from the 11th IAS Conference on Science. Lancet HIV. 2021 Aug;8(8):e459. doi: 10.1016/S2352-3018(21)00161-2. No abstract available.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 27, 2021): 183
• Original Estimated Enrollment (submitted: October 28, 2019): 175
• Actual Study Completion Date: September 13, 2023
• Actual Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Antiretroviral (ARV) naive with no use of any ARV within one month of screening. Use of pre-exposure prophylaxis (PrEP) (any duration), post-exposure prophylaxis (PEP) (any duration), or HIV-1 treatment (< 10 days therapy total) > 1 month prior to screening is permitted
• HIV-1 ribonucleic acid (RNA) ≥ 200 copies/mL at screening
• Cluster Determinant 4+ (CD4+) cell count ≥ 200 cells/microliter at screening

Key Exclusion Criteria:

• Current Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Dominican Republic, Puerto Rico, United States

Administrative Information

• NCT Number: NCT04143594
• Other Study ID Numbers: GS-US-200-4334
• 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: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gileadclinicaltrials.com/transparency-policy#Commitment

• 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: October 2023