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Safety, Pharmacokinetics, and Antiviral Activity of GS-6207 Administered Subcutaneously in HIV-1 Infected Adults

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ClinicalTrials.gov Identifier: NCT03739866
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE November 2, 2018
First Posted Date  ICMJE November 14, 2018
Last Update Posted Date November 7, 2019
Actual Study Start Date  ICMJE November 26, 2018
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2018)
Maximum Reduction of Plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 [ Time Frame: Day 1 through Day 10 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03739866 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 225 days ]
  • Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities [ Time Frame: Up to 225 days ]
  • Pharmacokinetic (PK) Parameter: AUCinf of GS-6207 [ 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.
  • PK Parameter: AUClast of GS-6207 [ 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.
  • PK Parameter: Cmax of GS-6207 [ 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.
  • Correlation Between Ct (Concentration at Day 10) of GS-6207 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 ]
  • Percentage of Participants Ever Achieving HIV-1 RNA < 50 copies/mL by Day 10 [ Time Frame: Day 10 ]
  • Percentage of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance [ Time Frame: Up to 225 days ]
  • Percentage of Participants Experience Any Emergence of TAF Resistance [ Time Frame: Up to 225 days ]
  • 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 ]
  • 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.
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2018)
  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 225 days ]
  • Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities [ Time Frame: Up to 225 days ]
  • Pharmacokinetic (PK) Parameter: AUCinf of GS-6207 [ 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.
  • PK Parameter: AUClast of GS-6207 [ 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.
  • PK Parameter: Cmax of GS-6207 [ 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.
  • Correlation Between Ct (Concentration at Day 10) of GS-6207 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 ]
  • Percentage of Participants Ever Achieving HIV-1 RNA < 50 copies/mL by Day 10 [ Time Frame: Day 10 ]
  • Percentage of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance [ Time Frame: Up to 225 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Pharmacokinetics, and Antiviral Activity of GS-6207 Administered Subcutaneously in HIV-1 Infected Adults
Official Title  ICMJE 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
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 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE
  • Drug: GS-6207
    Administered subcutaneously in the abdomen
  • Drug: Placebo
    Administered subcutaneously in the abdomen
  • Drug: B/F/TAF
    50/200/25 mg tablets administered orally once daily
    Other Name: Biktarvy®
  • Drug: TAF
    Tablets administered orally
Study Arms  ICMJE
  • Experimental: GS-6207 (Part A)

    Participants in Cohort 1 will receive a single dose of GS-6207 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 GS-6207 up to 450 mg on Day 1 or Cohorts 4-5 to receive a single dose of GS-6207 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.

    Interventions:
    • Drug: GS-6207
    • Drug: B/F/TAF
  • 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.

    Interventions:
    • Drug: Placebo
    • Drug: B/F/TAF
  • 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.

    Interventions:
    • Drug: B/F/TAF
    • Drug: TAF
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2019)
64
Original Estimated Enrollment  ICMJE
 (submitted: November 9, 2018)
32
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03739866
Other Study ID Numbers  ICMJE GS-US-200-4072
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP