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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Lenacapavir; Drug: B/F/TAF; Drug: Placebo; Drug: TAF

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group, Inc.
    • Sacramento, California, United States, 95817
      • One Community
    • Torrance, California, United States, 90502
      • The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Orlando, Florida, United States, 32803-1851
      • Orlando Immunology Center PA
    • West Palm Beach, Florida, United States, 33401
      • Triple O Research Institute, P.A.
  • Michigan
    • Berkley, Michigan, United States, 48072-3436
      • Be Well Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants, P.A.
    • Dallas, Texas, United States, 75208
      • AIDS Arms, Inc., DBA Prism Health North Texas
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A: Lenacapavir 20 mg; Participants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225.	Drug: Lenacapavir; Administered subcutaneously in the abdomen; Other Names: GS-6207; Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®
EXPERIMENTAL: Part A: Lenacapavir 50 mg; Participants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.	Drug: Lenacapavir; Administered subcutaneously in the abdomen; Other Names: GS-6207; Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®
EXPERIMENTAL: Part A: Lenacapavir 150 mg; Participants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.	Drug: Lenacapavir; Administered subcutaneously in the abdomen; Other Names: GS-6207; Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®
EXPERIMENTAL: Part A: Lenacapavir 450 mg; Participants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.	Drug: Lenacapavir; Administered subcutaneously in the abdomen; Other Names: GS-6207; Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®
EXPERIMENTAL: Part A: Lenacapavir 750 mg; Participants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.	Drug: Lenacapavir; Administered subcutaneously in the abdomen; Other Names: GS-6207; Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®
PLACEBO_COMPARATOR: Part A: Placebo; Participants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.	Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®; Drug: Placebo; Administered subcutaneously in the abdomen
EXPERIMENTAL: Part B: TAF 200 mg; Participants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.	Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®; Drug: TAF; Tablets administered orally
EXPERIMENTAL: Part B: TAF 600 mg; Participants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.	Drug: B/F/TAF; 50/200/25 mg tablets administered orally once daily; Other Names: Biktarvy®; Drug: TAF; Tablets administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10		Day 10
Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance		Day 10
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
Part B: Number of Participants Experiencing Any Emergence of TAF Resistance		Day 10
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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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; Boston, MA, USA
• 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 Conference; 2019 November 6-9; Basel, Switzerland.
• 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]. Presented at: 10th IAS Conference on HIV Science; 2019 21-24 July; Mexico City, Mexico.
• 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, Bondy S, Jin D, Hung M, Novikov N, Liu X, Villasenor AG, Cannizzaro CE, Hu EY, Anderson RL, Appleby TC, Lu B, Mwangi J, Liclican A, Niedziela-Majka A, Papalia GA, Wong MH, Leavitt SA, Xu Y, Koditek D, Stepan GJ, Yu H, Pagratis N, Clancy S, Ahmadyar S, Cai TZ, Sellers S, Wolckenhauer SA, Ling J, Callebaut C, Margot N, Ram RR, Liu YP, Hyland R, Sinclair GI, Ruane PJ, Crofoot GE, McDonald CK, Brainard DM, Lad L, Swaminathan S, Sundquist WI, Sakowicz R, Chester AE, Lee WE, Daar ES, Yant SR, Cihlar T. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020 Aug;584(7822):614-618. doi: 10.1038/s41586-020-2443-1. Epub 2020 Jul 1.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 26, 2018
• Primary Completion (ACTUAL): November 14, 2019
• Study Completion (ACTUAL): June 15, 2020

Study Registration Dates

• First Submitted: November 2, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (ACTUAL): November 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 9, 2021
• Last Update Submitted That Met QC Criteria: March 16, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: GS-US-200-4072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No