CompletedNCT03739866Updated Apr 9, 2021Results posted

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

A Phase 1 interventional study of Lenacapavir and Placebo in HIV-1 Infection, sponsored by Gilead Sciences. Completed at 12 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2021-04-09.

Sponsored by Gilead Sciences · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 53
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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.

Conditions studied

HIV-1 Infection

In context

Lead sponsor

Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

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 design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 53 participants (actual)

Study arms

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 · Drug: B/F/TAF
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 · Drug: B/F/TAF
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 · Drug: B/F/TAF
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 · Drug: B/F/TAF
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 · Drug: B/F/TAF
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: Placebo · Drug: B/F/TAF
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 · Drug: TAF
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 · Drug: TAF

Interventions

DrugLenacapavir
Administered subcutaneously in the abdomen
Also known as: GS-6207
DrugPlacebo
Administered subcutaneously in the abdomen
DrugB/F/TAF
50/200/25 mg tablets administered orally once daily
Also known as: Biktarvy®
DrugTAF
Tablets administered orally

What researchers measure

Primary outcomes

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).
Time frame: Day 1 through Day 10

Secondary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: Day 10
Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance
Time frame: 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.
Time frame: Day 10 through Day 225
Part B: Number of Participants Experiencing Any Emergence of TAF Resistance
Time frame: 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
Time frame: Day 10 through Day 225

Results

Posted Dec 9, 2020

Participant flow

Participants were enrolled at study sites in the United States. The first participant was screened on 26 November 2018. The last study visit occurred on 15 June 2020.

Participant flow — Overall Study
Milestone	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: Tenofovir Alafenamide (TAF) 200 mg	Part B: TAF 600 mg
Started	6	6	7	6	6	10	7	5
Completed	6	6	6	5	5	10	7	5
Not completed	0	0	1	1	1	0	0	0
Withdrew: Lost to follow-up	0	0	0	1	0	0	0	0
Withdrew: Enrolled but not treated	0	0	1	0	1	0	0	0

Outcome measures

PrimaryPart 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).

Time frame:: Day 1 through Day 10
Reported as:: Mean · log10 copies/mL

Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA
log10 copies/mL	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg
Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA	-1.35 ± 0.318	-1.79 ± 0.476	-1.76 ± 0.203	-2.20 ± 0.468	-2.26 ± 0.662	-0.17 ± 0.128	-0.75 ± 0.270	-0.91 ± 0.294

Statistical analysis

Part A: Lenacapavir 20 mg vs Part A: Placebo · t-test, 2 sided · p = <0.0001
Part A: Lenacapavir 50 mg vs Part A: Placebo · t-test, 2 sided · p = <0.0001
Part A: Lenacapavir 150 mg vs Part A: Placebo · t-test, 2 sided · p = <0.0001
Part A: Lenacapavir 450 mg vs Part A: Placebo · t-test, 2 sided · p = <0.0001
Part A: Lenacapavir 750 mg vs Part A: Placebo · t-test, 2 sided · p = <0.0001

SecondaryPart 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.

Time frame:: Day 1 through 225 days
Reported as:: Number · percentage of participants

Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
percentage of participants	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg
Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	83.3	100	83.3	100	80	70	85.7	100

SecondaryPart 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.

Time frame:: Day 1 through 225 days
Reported as:: Number · percentage of participants

Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities
percentage of participants	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg
Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities	83.3	83.3	100.0	66.7	100.0	80.0	100.0	80.0

SecondaryPart 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.

Time frame:: 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
Reported as:: Mean · h*ng/mL

Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV
h*ng/mL	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part B: TAF 200 mg	Part B: TAF 600 mg
Part A: Lenacapavir	6564.3 ± 2562.02	9124.1 ± 4443.03	31537.0 ± 6811.74	106041.1 ± 19939.41	181861.0 ± 73100.91	—	—
Part B: TAF	—	—	—	—	—	1270.3 ± 346.47	3556.1 ± 1396.81
Part B: TFV	—	—	—	—	—	2807.9 ± 904.23	13435.4 ± 1748.60

SecondaryPart 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.

Time frame:: 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
Reported as:: Mean · h*ng/mL

Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV
h*ng/mL	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part B: TAF 200 mg	Part B: TAF 600 mg
Part A: Lenacapavir	5084.3 ± 2143.03	7524.4 ± 4140.40	28866.4 ± 8247.37	102919.0 ± 19984.50	171173.9 ± 80524.85	—	—
Part B: TAF	—	—	—	—	—	1265.8 ± 350.75	3553.0 ± 1396.14
Part B: TFV	—	—	—	—	—	2706.7 ± 877.05	12682.5 ± 1780.31

SecondaryPart A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV

Cmax is defined as the maximum observed concentration of drug.

Time frame:: 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
Reported as:: Mean · ng/mL

Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV
ng/mL	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part B: TAF 200 mg	Part B: TAF 600 mg
Part A: Lenacapavir	3.0 ± 1.00	5.4 ± 4.00	17.1 ± 7.33	60.1 ± 16.92	116.6 ± 40.38	—	—
Part B: TAF	—	—	—	—	—	1919.0 ± 822.57	3934.0 ± 742.85
Part B: TFV	—	—	—	—	—	93.0 ± 36.97	371.0 ± 72.76

SecondaryPart 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.

Time frame:: 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
Reported as:: Mean · h*uM

Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF
h*uM	Part B: TAF 200 mg	Part B: TAF 600 mg
Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF	599.7 ± 299.36	7981.4 ± 3852.75

SecondaryPart 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.

Time frame:: 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
Reported as:: Mean · h*uM

Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF
h*uM	Part B: TAF 200 mg	Part B: TAF 600 mg
Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF	390.9 ± 372.31	7749.3 ± 3731.57

SecondaryPart B PK Parameter: Cmax of TFV-DP Metabolite of TAF

Cmax is defined as the maximum observed concentration of drug.

Time frame:: 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
Reported as:: Mean · uM

Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF
uM	Part B: TAF 200 mg	Part B: TAF 600 mg
Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF	8.5 ± 9.94	163.0 ± 118.75

SecondaryPart A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10

Time frame:: Day 10
Reported as:: Number · percentage of participants

Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10
percentage of participants	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo
Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10	0	16.7	0	16.7	20.0	0

SecondaryPart A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance

Time frame:: Day 10
Reported as:: Count of participants · Participants

Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance
Participants	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo
Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance	1	1	0	0	0	0

SecondaryPart 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.

Time frame:: Day 10 through Day 225
Reported as:: Count of participants · Participants

Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance
Participants	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo
Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance	0	0	0	0	0	0

SecondaryPart B: Number of Participants Experiencing Any Emergence of TAF Resistance

Time frame:: Day 10
Reported as:: Count of participants · Participants

Part B: Number of Participants Experiencing Any Emergence of TAF Resistance
Participants	Part B: TAF 200 mg	Part B: TAF 600 mg
Part B: Number of Participants Experiencing Any Emergence of TAF Resistance	0	0

SecondaryPart 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

Time frame:: Day 10 through Day 225

No measurements were reported for this outcome.

Adverse events

Collected over Day 1 through 225 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part A: Lenacapavir 20 mg	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
Part A: Lenacapavir 50 mg	0/6 (0%)	0/6 (0%)	6/6 (100%)
Part A: Lenacapavir 150 mg	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
Part A: Lenacapavir 450 mg	0/6 (0%)	1/6 (16.7%)	6/6 (100%)
Part A: Lenacapavir 750 mg	0/5 (0%)	0/5 (0%)	4/5 (80%)
Part A: Placebo	0/10 (0%)	1/10 (10%)	7/10 (70%)
Part B: TAF 200 mg	0/7 (0%)	0/7 (0%)	6/7 (85.7%)
Part B: TAF 600 mg	0/5 (0%)	0/5 (0%)	5/5 (100%)

Most frequent serious events

Most frequent serious events
Event	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg
Acute myocardial infarctionCardiac disorders	0/6	0/6	0/6	1/6	0/5	0/10	0/7	0/5
Atrial fibrillationCardiac disorders	0/6	0/6	0/6	1/6	0/5	0/10	0/7	0/5
Coronary artery diseaseCardiac disorders	0/6	0/6	0/6	1/6	0/5	0/10	0/7	0/5
Non-cardiac chest painGeneral disorders	0/6	0/6	0/6	1/6	0/5	0/10	0/7	0/5
Small intestinal obstructionGastrointestinal disorders	0/6	0/6	0/6	0/6	0/5	1/10	0/7	0/5

Most frequent other events

Showing 10 of 114

Most frequent other events
Event	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg
Injection site painGeneral disorders	0/6	4/6	4/6	4/6	4/5	3/10	0/7	0/5
Injection site erythemaGeneral disorders	1/6	1/6	4/6	2/6	2/5	1/10	0/7	0/5
Upper respiratory tract infectionInfections and infestations	0/6	0/6	0/6	4/6	0/5	0/10	1/7	2/5
NauseaGastrointestinal disorders	1/6	1/6	0/6	0/6	0/5	1/10	2/7	3/5
HeadacheNervous system disorders	2/6	0/6	0/6	1/6	0/5	2/10	2/7	3/5
Injection site indurationGeneral disorders	0/6	1/6	3/6	2/6	1/5	1/10	0/7	0/5
Injection site noduleGeneral disorders	0/6	1/6	1/6	2/6	2/5	0/10	0/7	0/5
ArthralgiaMusculoskeletal and connective tissue disorders	0/6	0/6	2/6	1/6	0/5	1/10	0/7	2/5
AnxietyPsychiatric disorders	0/6	0/6	0/6	0/6	0/5	0/10	0/7	2/5
NasopharyngitisInfections and infestations	1/6	1/6	2/6	2/6	0/5	1/10	1/7	0/5

Baseline characteristics

Safety Analysis Set included all participants who were randomized/enrolled and received at least 1 dose of study drug.

Age, Continuous
Age, Continuous(years)	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg	Total
Mean	33 ± 4.4	36 ± 14.4	39 ± 11.5	36 ± 15.5	37 ± 17.7	29 ± 9.3	29 ± 8.7	40 ± 8.7	34 ± 11.5

Sex: Female, Male
Sex: Female, Male(Participants)	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg	Total
Female	0	0	1	0	2	1	0	0	4
Male	6	6	5	6	3	9	7	5	47

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg	Total
Hispanic or Latino	1	0	0	1	3	1	5	2	13
Not Hispanic or Latino	5	6	6	5	2	9	2	3	38
Unknown or Not Reported	0	0	0	0	0	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg	Total
Race — Asian	1	1	0	0	0	1	0	0	3
Race — Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	1	0	1
Race — Black	0	2	3	2	1	4	1	0	13
Race — White	4	3	2	4	3	5	5	5	31
Race — Other	1	0	1	0	1	0	0	0	3

HIV-1 RNA
HIV-1 RNA(log10 copies/mL)	Part A: Lenacapavir 20 mg	Part A: Lenacapavir 50 mg	Part A: Lenacapavir 150 mg	Part A: Lenacapavir 450 mg	Part A: Lenacapavir 750 mg	Part A: Placebo	Part B: TAF 200 mg	Part B: TAF 600 mg	Total
Mean	4.46 ± 0.428	4.44 ± 0.328	4.48 ± 0.161	4.52 ± 0.190	4.56 ± 0.305	4.50 ± 0.371	4.23 ± 0.621	4.97 ± 0.439	4.50 ± 0.403

Study locations

12 sites

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

References and documents

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. PubMed 32612233 ↗
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 documents

Study protocol · Jun 13, 2019
Statistical analysis plan · Sep 14, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 9, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03739866
Lead sponsor: Gilead Sciences
Responsible party: Sponsor
First posted: Nov 14, 2018
Start date: Nov 26, 2018
Primary completion: Nov 14, 2019
Completion: Jun 15, 2020
Results posted: Dec 9, 2020
Last update: Apr 9, 2021

Study contacts

Gilead Study Director

study director · Gilead Sciences

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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