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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04143594
Recruitment Status : Active, not recruiting
First Posted : October 29, 2019
Results First Posted : December 19, 2022
Last Update Posted : December 19, 2022
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE October 28, 2019
First Posted Date  ICMJE October 29, 2019
Results First Submitted Date  ICMJE September 29, 2022
Results First Posted Date  ICMJE December 19, 2022
Last Update Posted Date December 19, 2022
Actual Study Start Date  ICMJE November 22, 2019
Actual Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Study to Evaluate the Safety and Efficacy of Lenacapavir in Combination With Other Antiretroviral Agents in People Living With HIV
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1-infection
Intervention  ICMJE
  • 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  ICMJE
  • 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 *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 27, 2021)
183
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2019)
175
Estimated Study Completion Date  ICMJE April 2024
Actual Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Dominican Republic,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04143594
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Current Responsible Party Gilead Sciences
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Gilead Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date November 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP