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

HIV-1-infection Clinical Trial

— CALIBRATE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04143594
• Other study ID #: GS-US-200-4334
• Status: Completed
• Phase: Phase 2
• Start date: November 22, 2019
• Est. completion date: September 13, 2023

Study information

• Verified date: October 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: September 13, 2023
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Oral Lenacapavir
Tablets administered without regard to food
• F/TAF
Tablets administered without regard to food
• Subcutaneous Lenacapavir
Administered in the abdomen via subcutaneous injections
• TAF
Tablets administered without regard to food
• BIC
Tablets administered without regard to food
• B/F/TAF
Tablets administered without regard to food

Locations

Country	Name	City	State
Dominican Republic	Instituto Dominicano de Estudios Virológicos (IDEV)	Santo Domingo
Puerto Rico	Clinical Research Puerto Rico	San Juan
Puerto Rico	HOPE Clinical Research	San Juan
Puerto Rico	Proyecto ACTU, School of Medicine, University of Puerto Rico	San Juan
United States	Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)	Annandale	Virginia
United States	Atlanta ID Group, PC	Atlanta	Georgia
United States	August University Medical Center	Augusta	Georgia
United States	University of Colorado, Denver, University of Colorado Hospital	Aurora	Colorado
United States	Central Texas Clinical Research	Austin	Texas
United States	St Hope Foundation	Bellaire	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	Montefiore Medical Center	Bronx	New York
United States	Howard Brown Health Center	Chicago	Illinois
United States	Northstar Healthcare	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case Clinical Research Site/University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	North Texas Infectious Diseases Consultants, P.A.	Dallas	Texas
United States	Prism Health North Texas	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Midland Florida Clinical Research Center, LLC	DeLand	Florida
United States	Denver Public Health	Denver	Colorado
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Texas Centers for Infectious Disease Associates	Fort Worth	Texas
United States	East Carolina University, The Brody School of Medicine	Greenville	North Carolina
United States	Floridian Clinical Research	Hialeah	Florida
United States	The Crofoot Research Center, Inc.	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Indiana University Infectious Diseases Research	Indianapolis	Indiana
United States	KC CARE Health Center	Kansas City	Missouri
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Mills Clinical Research at Men's Health Foundation	Los Angeles	California
United States	Ruane Clinical Research Group Inc	Los Angeles	California
United States	Mercer University, Department of Internal Medicine	Macon	Georgia
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	AHF-The Kinder Medical Group	Miami	Florida
United States	AIDS Healthcare Foundation - South Beach	Miami Beach	Florida
United States	Yale University; School of Medicine	New Haven	Connecticut
United States	AHF-Midtown	New York	New York
United States	Orlando Immunology Center	Orlando	Florida
United States	Eisenhower Health Center at Rimrock	Palm Springs	California
United States	Pueblo Family Physicians	Phoenix	Arizona
United States	Valleywise Community Health Center - McDowell	Phoenix	Arizona
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Chatham County Health Department	Savannah	Georgia
United States	Peter Shalit, M.D.	Seattle	Washington
United States	St. John Newland Medical Associates	Southfield	Michigan
United States	MultiCare Rockwood HIV Critical Care Clinic	Spokane	Washington
United States	St. Joseph's Hospital Comprehensive Research Institute	Tampa	Florida
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Washington Health Institute	Washington	District of Columbia
United States	Whitman-Walker Institute, Inc.	Washington	District of Columbia
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Dominican Republic,  Puerto Rico, 

References & Publications (2)

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)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).	Week 54
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm	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).	Week 28
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm	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).	Week 38
Secondary	Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm		Week 80
Secondary	Change From Baseline in Log10 HIV-1 RNA at Week 28		Baseline; Week 28
Secondary	Change From Baseline in Log10 HIV-1 RNA at Week 38		Baseline; Week 38
Secondary	Change From Baseline in Log10 HIV-1 RNA at Week 54		Baseline; Week 54
Secondary	Change From Baseline in Log10 HIV-1 RNA at Week 80		Baseline; Week 80
Secondary	Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 28		Baseline; Week 28
Secondary	Change From Baseline in CD4+ Cell Count at Week 38		Baseline; Week 38
Secondary	Change From Baseline in CD4+ Cell Count at Week 54		Baseline; Week 54
Secondary	Change From Baseline in CD4+ Cell Count at Week 80		Baseline; Week 80
Secondary	Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	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.	First dose date up to 54 weeks
Secondary	Percentage of Participants Who Experienced Laboratory Abnormalities	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.	First dose date up to 54 weeks
Secondary	Pharmacokinetics (PK) of TAF (Tenofovir Alafenamide)and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) 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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Secondary	PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) 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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Secondary	PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) 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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Secondary	PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) 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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
Secondary	PK of TAF and TFV: AUClast at Weeks 16, 22, or 28	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of TAF and TFV: Cmax at Weeks 16, 22, or 28	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of TAF and TFV: Tmax at Weeks 16, 22, or 28	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of TFV: Clast at Weeks 16, 22, or 28	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of TAF: AUClast at Week 38	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of TAF: Cmax at Week 38	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of TAF: Tmax at Week 38	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22	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.	0 hours (Predose) and at 1, 2, and 6 hours postdose
Secondary	PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22	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.	0 hours (Predose) and at 1, 2, and 6 hours postdose
Secondary	PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22	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.	0 hours (Predose) and at 1, 2, and 6 hours postdose
Secondary	PK of Bictegravir (BIC): AUClast at Week 38	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of BIC: Cmax at Week 38	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of BIC: Tmax at Week 38	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Secondary	PK of BIC: Clast at Week 38	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.	0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

External Links

•   Gilead Clinical Trials Website