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HIV-1 InfectionPhase 1NCT03739866

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

A Phase 1 study testing Lenacapavir, B/F/TAF and TAF in people with HIV-1 Infection, run by Gilead Sciences at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV-1 Infection
What is being tested?
Lenacapavir, B/F/TAF and TAF
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
53 participants
Where
12 sitesUnited States
Study dates
26 Nov 2018to 15 Jun 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Be Well Medical Center

    Berkley, Michigan, 48072-3436

  • AIDS Arms, Inc., DBA Prism Health North Texas

    Dallas, Texas, 75208

  • North Texas Infectious Diseases Consultants, P.A.

    Dallas, Texas, 75246

  • Tarrant County Infectious Disease Associates

    Fort Worth, Texas, 76104

  • Midway Immunology and Research Center

    Ft. Pierce, Florida, 34982

  • The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)

    Houston, Texas, 77098

  • Ruane Clinical Research Group, Inc.

    Los Angeles, California, 90036

  • Mills Clinical Research

    Los Angeles, California, 90069

  • Orlando Immunology Center PA

    Orlando, Florida, 32803-1851

  • One Community

    Sacramento, California, 95817

  • The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • Triple O Research Institute, P.A.

    West Palm Beach, Florida, 33401

Other trials in United States

About this study

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

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
HIV-1 Infection
Being tested
Lenacapavir, Placebo, B/F/TAF, TAF

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenacapavirDrug

    Also called GS-6207

    Administered subcutaneously in the abdomen

  • PlaceboDrug

    Administered subcutaneously in the abdomen

  • B/F/TAFDrug

    Also called Biktarvy®

    50/200/25 mg tablets administered orally once daily

  • TAFDrug

    Tablets administered orally

Study groups in NCT03739866
Study groupRoleWhat they receive
Part A: Lenacapavir 20 mgExperimentalParticipants 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.
Receives: Drug: Lenacapavir; Drug: B/F/TAF
Part A: Lenacapavir 50 mgExperimentalParticipants 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.
Receives: Drug: Lenacapavir; Drug: B/F/TAF
Part A: Lenacapavir 150 mgExperimentalParticipants 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.
Receives: Drug: Lenacapavir; Drug: B/F/TAF
Part A: Lenacapavir 450 mgExperimentalParticipants 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.
Receives: Drug: Lenacapavir; Drug: B/F/TAF
Part A: Lenacapavir 750 mgExperimentalParticipants 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.
Receives: Drug: Lenacapavir; Drug: B/F/TAF
Part A: PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo; Drug: B/F/TAF
Part B: TAF 200 mgExperimentalParticipants 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.
Receives: Drug: B/F/TAF; Drug: TAF
Part B: TAF 600 mgExperimentalParticipants 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.
Receives: Drug: B/F/TAF; Drug: TAF

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Day 1 through Day 10

Secondary outcomes (13)

  1. 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.

    Measured: Day 1 through 225 days

  2. 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.

    Measured: Day 1 through 225 days

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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.

    Measured: 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

  7. 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.

    Measured: 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

  8. Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF

    Cmax is defined as the maximum observed concentration of drug.

    Measured: 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

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

    Measured: Day 10

  10. Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance

    Measured: Day 10

  11. 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.

    Measured: Day 10 through Day 225

  12. Part B: Number of Participants Experiencing Any Emergence of TAF Resistance

    Measured: Day 10

  13. 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

    Measured: Day 10 through Day 225

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2018
  2. Study start26 Nov 2018
  3. Primary completion14 Nov 2019
  4. Study completion15 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03739866
Sponsor's protocol ID
GS-US-200-4072
Status last verified
Mar 2021
First submitted
2 Nov 2018
Last updated
9 Apr 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lenacapavir, B/F/TAF and TAF in people with HIV-1 Infection, run by Gilead Sciences at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A and Part B: Maximum Reduction From Day 1 (Baseline) Through Day 10 in Plasma HIV-1 RNA (time frame: Day 1 through Day 10). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03739866, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2021.

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