Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Lenacapavir Administered Subcutaneously in Human Immunodeficiency Virus (HIV) -1 Infected Adults

HIV-1 Infection Clinical Trial

Official title:

A Phase 1b Randomized, Double-Blinded, Placebo Controlled, Multi-Cohort Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-6207 Administered Subcutaneously in HIV-1 Infected Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03739866
• Other study ID #: GS-US-200-4072
• Status: Completed
• Phase: Phase 1
• Start date: November 26, 2018
• Est. completion date: June 15, 2020

Study information

• Verified date: March 2021
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are: Part A: To evaluate the short-term antiviral activity of lenacapavir (formerly GS-6207) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 compared to placebo in HIV-1 infected adults who are antiretroviral treatment naive or are experienced but capsid inhibitor (CAI) naive. Part B: To evaluate the short-term antiviral activity of tenofovir alafenamide (TAF) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 in HIV-1 infected adult subjects who are antiretroviral treatment naïve or are experienced but without resistance to TAF.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: June 15, 2020
• Est. primary completion date: November 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

• Plasma HIV-1 RNA = 5,000 copies/mL but = 400,000 copies/mL and CD4+ cell count > 200 cells/mm^3
• Treatment naive or experienced but CAI (for Part A only) and integrase strand transfer inhibitor (INSTI) naïve, and have not received any antiretroviral therapy (ART) within 12 weeks of screening
• Screening genotype report must show sensitivity to B/F/TAF to allow its initiation on Day 10
• Screening genotype report must show sensitivity to at least one agent in either non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) class to allow its use as part of standard of care oral antiretroviral treatment in the future
• Have adequate renal function (estimated glomerular filtration rate = 70 mL/min)
• No clinically significant abnormalities in electrocardiography (ECG) at Screening
• Willing to initiate B/F/TAF on Day 10 after completion of all assessments

Key Exclusion Criteria:

• Pregnant or lactating females Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Lenacapavir
Administered subcutaneously in the abdomen
• Placebo
Administered subcutaneously in the abdomen
• B/F/TAF
50/200/25 mg tablets administered orally once daily
• TAF
Tablets administered orally

Locations

Country	Name	City	State
United States	Be Well Medical Center	Berkley	Michigan
United States	AIDS Arms, Inc., DBA Prism Health North Texas	Dallas	Texas
United States	North Texas Infectious Diseases Consultants, P.A.	Dallas	Texas
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)	Houston	Texas
United States	Mills Clinical Research	Los Angeles	California
United States	Ruane Clinical Research Group, Inc.	Los Angeles	California
United States	Orlando Immunology Center PA	Orlando	Florida
United States	One Community	Sacramento	California
United States	The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (5)

Daar ES, McDonald C, Crofoot G, Ruane P, Sinclair G, Begley R, et al. Dose-response relationship of subcutaneous long-acting HIV capsid inhibitor GS-6207 [Poster]. Presented at: Conference on Retroviruses and Opportunistic Infections; 2020 March 8-11; Bos

Daar ES, McDonald C, Crofoot G, Ruane P, Sinclair G, Patel H, et al. Safety and antiviral activity over 10 days following a single dose of subcutaneous GS-6207, a first-in-class, long acting HIV capsid inhibitor in people living with HIV [Poster]. Present

Daar ES, McDonald C, Crofoot G, Ruane P, Sinclair G, Patel H, et al. Single doses of long acting capsid inhibitor GS-6207 administered by subcutaneous injection are safe and efficacious in people living with HIV [Poster]. Presented at: 17th European AIDS

Link JO, Rhee MS, Tse WC, Zheng J, Somoza JR, Rowe W, Begley R, Chiu A, Mulato A, Hansen D, Singer E, Tsai LK, Bam RA, Chou CH, Canales E, Brizgys G, Zhang JR, Li J, Graupe M, Morganelli P, Liu Q, Wu Q, Halcomb RL, Saito RD, Schroeder SD, Lazerwith SE, Bo — View Citation

Margot N, Ram R, Parvangada P, Martin R, Hyland R, Rhee M, Callebaut C. Lenacapavir resistance analysis in a phase Ib clinical proof-of-concept study [oral]. Presented at: HIV Glasgow; 2020 October 5 - 8; Virtual.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA	Maximum reduction is defined as the minimum of change from baseline in plasma HIV-1 RNA (i.e. smallest change in HIV-RNA from baseline).	Day 1 through Day 10
Secondary	Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as any AE with an onset date on or after the study drug start date.	Day 1 through 225 days
Secondary	Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.	Day 1 through 225 days
Secondary	Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV	AUCinf is defined as area under the concentration versus time curve from time zero to infinity.	Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10
Secondary	Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV	AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.	Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10
Secondary	Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV	Cmax is defined as the maximum observed concentration of drug.	Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10
Secondary	Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF	AUCinf is defined as area under the concentration versus time curve from time zero to infinity.	Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10
Secondary	Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF	AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.	Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10
Secondary	Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF	Cmax is defined as the maximum observed concentration of drug.	Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10
Secondary	Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10		Day 10
Secondary	Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance		Day 10
Secondary	Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance	Post-Monotherapy Resistance Analysis Population analyzed for this outcome measure included any participant who received at least 1 dose of study drug/placebo, maintained their study drug regimen, & met one of following virologic failure criteria: HIV-1 RNA = 50 copies/mL & < 1 log10 HIV-1 RNA reduction from Day 10 at Day 57 visit, confirmed at a scheduled or unscheduled visit at least 2 weeks following Day 57; At any visit following Day 10, after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA to = 50 copies/mL, which was subsequently confirmed at following scheduled or unscheduled visit; OR At any visit, a > 1 log10 increase in HIV-1 RNA from nadir, which was subsequently confirmed at following scheduled or unscheduled visit; Any participant with HIV-1 RNA = 50 copies/mL at study endpoint or study discontinuation who didn't meet any of criteria above also had protease (PR)/reverse transcriptase (RT), integrase (IN), &capsid (CA) genotyping & phenotyping performed.	Day 10 through Day 225
Secondary	Part B: Number of Participants Experiencing Any Emergence of TAF Resistance		Day 10
Secondary	Part B: Number of Participants Experiencing Any Emergence of TAF Resistance	TAF Resistance testing was performed for any participant meeting Post-Monotherapy Resistance Analysis Population criteria - it included any participant who received at least 1 dose of study drug/placebo, maintained their study drug regimen, & met one of the following virologic failure criteria: HIV-1 RNA =50 copies/mL & < 1 log10 HIV-1 RNA reduction from D10 at the D57 visit, confirmed at scheduled or unscheduled visit at least 2 weeks following D57; At any visit following D10, after achieving HIV-1 RNA< 50 copies/mL, a rebound in HIV-1 RNA to =50 copies/mL, which was subsequently confirmed at the following scheduled/unscheduled visit; OR At any visit, a > 1 log10 increase in HIV-1 RNA from nadir, which was subsequently confirmed at the following scheduled or unscheduled visit; Any participant with HIV-1 RNA =50 copies/mL at study endpoint or study discontinuation who didn't meet any of the criteria above also had PR/RT, IN, and CA genotyping & phenotyping performed.; D = Day	Day 10 through Day 225