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Safety, Pharmacokinetics, and Antiviral Activity of Lenacapavir Administered Subcutaneously in HIV-1 Infected Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03739866
Recruitment Status : Active, not recruiting
First Posted : November 14, 2018
Last Update Posted : April 16, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

This study has 2 parts: Part A (Cohorts 1-5) and Part B (Cohorts 6-8).

The primary objectives of this study are:

Part A: To evaluate the short-term antiviral activity of lenacapavir (formerly GS-6207) 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.


Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: Lenacapavir Drug: Placebo Drug: B/F/TAF Drug: TAF Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 26, 2018
Actual Primary Completion Date : November 14, 2019
Estimated Study Completion Date : June 16, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Lenacapavir (Part A)

Participants in Cohort 1 will receive a single dose of lenacapavir 150 mg on Day 1. Following review of preliminary safety and pharmacokinetic (PK) data, participants will be enrolled in Cohorts 2-3 to receive a single dose of lenacapavir up to 450 mg on Day 1 or Cohorts 4-5 to receive a single dose of lenacapavir up to 900 mg on Day 1.

After completion of all assessments, at Day 10, participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for the remainder of the study.

Drug: Lenacapavir
Administered subcutaneously in the abdomen
Other Name: GS-6207

Drug: B/F/TAF
50/200/25 mg tablets administered orally once daily
Other Name: Biktarvy®

Placebo Comparator: Placebo

Participants will receive a single dose of placebo on Day 1.

After completion of all assessments, at Day 10, participants will receive B/F/TAF for the remainder of the study.

Drug: Placebo
Administered subcutaneously in the abdomen

Drug: B/F/TAF
50/200/25 mg tablets administered orally once daily
Other Name: Biktarvy®

Experimental: TAF (Part B)

Participants will receive a single dose of TAF 200 mg on Day 1. Following review of preliminary safety and PK data, participants will be enrolled in Cohorts 7-8 to receive a single dose of TAF up to 600 mg on Day 1.

After completion of all assessments, at Day 10, participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for the remainder of the study.

Drug: B/F/TAF
50/200/25 mg tablets administered orally once daily
Other Name: Biktarvy®

Drug: TAF
Tablets administered orally




Primary Outcome Measures :
  1. Maximum Reduction of Plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 [ Time Frame: Day 1 through Day 10 ]

Secondary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 225 days ]
  2. Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities [ Time Frame: Up to 225 days ]
  3. Pharmacokinetic (PK) Parameter: AUCinf of lenacapavir [ Time Frame: Predose and 1, 2, 4, 8, 12, and 24 hours post dose on Day 1; Days 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 225 ]
    AUCinf is defined as the concentration of drug extrapolated to infinite time.

  4. PK Parameter: AUClast of lenacapavir [ Time Frame: Predose and 1, 2, 4, 8, 12, and 24 hours post dose on Day 1; Days 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 225 ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  5. PK Parameter: Cmax of lenacapavir [ Time Frame: Predose and 1, 2, 4, 8, 12, and 24 hours post dose on Day 1; Days 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 225 ]
    Cmax is defined as the maximum observed concentration of drug.

  6. Correlation Between Ct (Concentration at Day 10) of lenacapavir and the Maximum Reduction of Plasma HIV-1 RNA (log10 copies/mL) from Baseline through Day 10 Estimated using the Pearson Correlation Analysis [ Time Frame: Baseline through Day 10 ]
  7. Percentage of Participants Ever Achieving HIV-1 RNA < 50 copies/mL by Day 10 [ Time Frame: Day 10 ]
  8. Percentage of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance [ Time Frame: Up to 225 days ]
  9. Percentage of Participants Experience Any Emergence of TAF Resistance [ Time Frame: Up to 225 days ]
  10. Pharmacokinetic (PK) Parameter: AUCinf of TAF (and its metabolite) [ Time Frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 and 48 hours post dose on Day 1; Days 4, 5, (if possible), 6 (if possible), 7, 8, 9, and 10 ]
  11. PK Parameter: AUClast of TAF (and its metabolite) [ Time Frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 and 48 hours post dose on Day 1; Days 4, 5, (if possible), 6 (if possible), 7, 8, 9, and 10 ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  12. PK Parameter: Cmax of TAF (and its metabolite) [ Time Frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 and 48 hours post dose on Day 1; Days 4, 5, (if possible), 6 (if possible), 7, 8, 9, and 10 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 ECG at Screening
  • Willing to initiate B/F/TAF on Day 10 after completion of all assessments

Key Exclusion Criteria:

  • Pregnant or lactating

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03739866


Locations
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United States, California
Ruane Clinical Research Group, Inc.
Los Angeles, California, United States, 90036
Mills Clinical Research
Los Angeles, California, United States, 90069
One Community
Sacramento, California, United States, 95817
The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
Torrance, California, United States, 90502
United States, Florida
Gary Richmond, MD, PA, Inc.
Fort Lauderdale, Florida, United States, 33316
Midway Immunology and Research Center
Fort Pierce, Florida, United States, 34982
Orlando Immunology Center PA
Orlando, Florida, United States, 32803-1851
Triple O Research Institute, P.A.
West Palm Beach, Florida, United States, 33401
United States, Michigan
Be Well Medical Center
Berkley, Michigan, United States, 48072-3436
United States, Texas
AIDS Arms, Inc., DBA Prism Health North Texas
Dallas, Texas, United States, 75208
North Texas Infectious Diseases Consultants, P.A.
Dallas, Texas, United States, 75246
Tarrant County Infectious Disease Associates
Fort Worth, Texas, United States, 76104
The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)
Houston, Texas, United States, 77098
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03739866    
Other Study ID Numbers: GS-US-200-4072
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: April 16, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No