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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT05585307
Registration number
NCT05585307
Ethics application status
Date submitted
14/10/2022
Date registered
18/10/2022
Date last updated
8/05/2025
Titles & IDs
Public title
Study of Novel Antiretrovirals in Participants With HIV-1
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Scientific title
An Umbrella Phase 1b, Open-label, Multi-Cohort Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1
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Secondary ID [1]
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GS-US-544-5905
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
HIV-1-infection
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Bavtavirine
Treatment: Drugs - B/F/TAF
Treatment: Drugs - Standard of Care (Substudy 01)
Treatment: Drugs - GS-1720
Treatment: Drugs - Standard of Care (Substudy 02)
Treatment: Drugs - GS-6212
Treatment: Drugs - Standard of Care (Substudy 03)
Experimental: Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal) - Participants receive a single dose of bavtavirine 675 mg tablet with a high-fat meal on Day 1. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of B/F/TAF, or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 39.
Experimental: Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal) - Participants receive a single dose of bavtavirine 1200 mg tablet with a low-fat meal on Day 1. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Experimental: Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal) - Participants receive bavtavirine 900 mg tablet with a high-fat meal on Days 1 and 2. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Experimental: Substudy 02: Cohort 1: GS-1720 450 mg - Participants receive a single dose of GS-1720 450 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Experimental: Substudy 02: Cohort 2: GS-1720 150 mg - Participants receive a single dose of GS-1720 150 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Experimental: Substudy 02: Cohort 3: GS-1720 30 mg - Participants receive a single dose of GS-1720 30 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Experimental: Substudy 02: Cohort 4: GS-1720 900 mg - Participants receive a single dose of GS-1720 900 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Experimental: Substudy 03: Cohort 1: GS- 6212 100 mg - Participants receive GS-6212 100 mg tablet twice daily on Days 1 through 10. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 25.
Treatment: Drugs: Bavtavirine
Administered orally
Treatment: Drugs: B/F/TAF
Administered orally
Treatment: Drugs: Standard of Care (Substudy 01)
Antiretroviral therapy, administered orally
Non-NNRTIs, examples: ABC/DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)
Treatment: Drugs: GS-1720
Administered orally
Treatment: Drugs: Standard of Care (Substudy 02)
Antiretroviral therapy, administered orally
Example INSTIs: DTG/ABC/3TC or DTG/3TC
Treatment: Drugs: GS-6212
Administered orally
Treatment: Drugs: Standard of Care (Substudy 03)
Antiretroviral therapy, administered orally
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Substudies 01, 02 and 03: Change From Baseline in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (log10 Copies/mL) at Day 11 Relative to Historical Placebo Data
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Assessment method [1]
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Timepoint [1]
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Baseline, Day 11
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Secondary outcome [1]
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Substudies 01, 02 and 03: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data
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Assessment method [1]
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Timepoint [1]
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Baseline, Day 8
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Secondary outcome [2]
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Substudies 01, 02 and 03: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
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Assessment method [2]
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An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as any AEs with an onset date on or after the study drug start date. Percentages were rounded-off.
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Timepoint [2]
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First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)
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Secondary outcome [3]
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Substudies 01, 02 and 03: Percentage of Participants With Graded Laboratory Abnormalities
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Assessment method [3]
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Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any time postbaseline. Laboratory abnormalities were graded using Division of AIDS (DAIDS) scale with grade 0 to 4 where 0 = no grade; 1 = mild, 2 = moderate, 3 = severe; 4 = potentially life-threatening. Participants with at least a 1 grade increased from baseline for an individual laboratory test where the maximum post baseline laboratory abnormality was 1) grade 1 or higher and 2) grade 3 or higher were reported. The maximum postbaseline toxicity grade across all tests for an individual participant was used in analysis. Percentages were rounded-off.
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Timepoint [3]
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First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)
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Secondary outcome [4]
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Substudy 01: Pharmacokinetic (PK) Parameter: Cmax of Bavtavirine
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Assessment method [4]
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Cmax was defined as the maximum observed concentration of drug.
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Timepoint [4]
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Cohorts 1, 2 and 3 (Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose); Cohort 3: Day 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
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Secondary outcome [5]
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Substudy 01: PK Parameter: AUC of Bavtavirine
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Assessment method [5]
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AUC was defined as the area under the concentration versus time curve.
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Timepoint [5]
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Day 1 up to Day 11
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Secondary outcome [6]
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Substudy 01: PK Parameter: Plasma Concentration of Bavtavirine
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Assessment method [6]
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Timepoint [6]
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Days 8 and 11
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Secondary outcome [7]
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Substudy 02: PK Parameter: Cmax of GS-1720
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Assessment method [7]
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Cmax was defined as the maximum observed concentration of drug.
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Timepoint [7]
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Days 1 and 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and (optional) 12 hours postdose
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Secondary outcome [8]
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Substudy 02: PK Parameter: AUC of GS-1720
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Assessment method [8]
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AUC was defined as the area under the concentration versus time curve.
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Timepoint [8]
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Day 1 up to Day 11
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Secondary outcome [9]
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Substudy 02: PK Parameter: Plasma Concentration of GS-1720
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Assessment method [9]
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Timepoint [9]
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Days 8 and 11
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Secondary outcome [10]
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Substudy 03: PK Parameter: Cmax of GS-6212
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Assessment method [10]
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Cmax was defined as the maximum observed concentration of drug.
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Timepoint [10]
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Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)
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Secondary outcome [11]
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Substudy 03: PK Parameter: AUC0-8h of GS-6212
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Assessment method [11]
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AUC0-8h was defined as the area under the concentration versus time curve spanning from 0 to 8 hours post dose.
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Timepoint [11]
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Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)
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Secondary outcome [12]
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Substudy 03: PK Parameter: AUCtau of GS-6212
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Assessment method [12]
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AUCtau was defined as the area under the curve from time zero to end of dosing interval.
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Timepoint [12]
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Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)
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Secondary outcome [13]
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Substudy 03: PK Parameter: Plasma Concentration of GS-6212
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Assessment method [13]
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Timepoint [13]
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Days 1 and 10: 8 hours postdose
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Secondary outcome [14]
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Substudy 03: PK Parameter: Ctrough of GS-6212 (Day 10)
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Assessment method [14]
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Ctrough was defined as concentration at the end of the dosing interval.
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Timepoint [14]
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Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)
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Secondary outcome [15]
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Substudy 03: PK Parameter: Cavg of GS-6212 (Day 10)
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Assessment method [15]
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Cavg was defined as average plasma concentration during dose administration.
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Timepoint [15]
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Day 10 (predose to 8 hours postdose)
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Secondary outcome [16]
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Substudies 01, 02 and 03: Percentage of Participants at Any Measurement Achieving HIV-1 RNA < 50 Copies/mL by Day 11 at Each Dose Level
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Assessment method [16]
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Percentages were rounded-off.
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Timepoint [16]
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Up to Day 11
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Secondary outcome [17]
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Substudies 01, 02 and 03: Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug
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Assessment method [17]
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The antiretroviral (ARV) class of given drugs would be BVY or NNRTIs (Substudy 01) or INSTIs (Substudy 02) or INSTIs (Substudy 03). Percentages were rounded-off.
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Timepoint [17]
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Up to Day 11
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Secondary outcome [18]
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Substudy 01: Maximum Inhibitory Quotient (IQ) of Bavtavirine by Mean Plasma Concentration (Ct) up to Day 11
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Assessment method [18]
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Inhibitory quotient was calculated as the ratio of bavtavirine in vivo exposure to in vitro plasma concentration. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ = 2 indicated higher reduction in viral load with less rebound.
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Timepoint [18]
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Up to Day 11
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Secondary outcome [19]
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Substudy 02: Inhibitory Quotient (IQ) of GS-1720 by Mean Plasma Concentration (Ct) at Day 11
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Assessment method [19]
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Inhibitory quotient was calculated as the ratio of GS-1720 in vivo exposure to in vitro plasma concentration. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ = 2 indicated higher reduction in viral load with less rebound.
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Timepoint [19]
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Day 11
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Secondary outcome [20]
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Substudy 03: Inhibitory Quotient (IQ) of GS-6212 by Ctrough at Day 11
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Assessment method [20]
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Ctrough is the plasma concentration of the drug just before the next dose. Inhibitory quotient was calculated as the ratio of GS-1720 in vivo exposure to in vitro Ctrough. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ = 2 indicated higher reduction in viral load with less rebound.
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Timepoint [20]
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Day 11
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Eligibility
Key inclusion criteria
Key
All Substudies:
* Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) = 5000 copies/mL but = 400,000 copies/mL at screening.
* Cluster of differentiation 4 (CD4) cell count > 200 cells/mm^3 at screening.
* Antiretroviral (ARV) treatment-naive or treatment-experienced but naive to the investigational ARV drug class being investigated in the given substudy and have not received any ARV within 12 weeks of screening, including medications received for pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) (note that current or prior receipt of long acting (LA) parenteral ARVs such as monoclonal antibodies (mAbs) targeting HIV-1, injectable cabotegravir (CAB), or injectable rilpivirine (RPV) is exclusionary).
* Have adequate renal function (estimated glomerular filtration rate (eGFR) = 70 mL/min/1.73 m^2)
* No clinically significant abnormalities in electrocardiogram (ECG) at screening.
Substudy-01, Substudy-02, and Substudy-03:
* Participants in substudy-01 should be willing to initiate a non-NNRTI based SOC ART on Day 11.
* Participants in substudy-02 and Substudy-03 should be willing to initiate any SOC ART on Day 11.
* Willing and able to comply with meal requirements on dosing days.
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Minimum age
18
Years
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Maximum age
65
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
All Substudies:
* Known historical genotypic or phenotypic resistance to 4 major ARV classes (nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), integrase strand-transfer inhibitor (INSTI)).
* History of an AIDS-defining condition including present at the time of screening.
* Active, serious infections (other than HIV-1) requiring therapy and including active tuberculosis infection < 30 days prior to randomization.
* History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
* Any other serious or active clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.
* Hepatitis C virus (HCV) antibody positive and detectable HCV RNA.
* Chronic hepatitis B virus (HBV) infection, as determined by either:
* Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit, or
* Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.
* Hepatic transaminases (aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) > 5 x upper limit of normal (ULN).
* Current alcohol or substance use judged by the investigator to potentially interfere with individual study compliance.
* Positive serum pregnancy test at screening or a positive pregnancy test prior to Day 1.
* Individuals with plan to breastfeed during the study period including the protocol-defined follow-up period.
* Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol. Any prescription medications or over the counter medications, including herbal products, within 28 days prior to start of study drug dosing must be reviewed and approved by the sponsor, with the exception of vitamins and/or acetaminophen and/or ibuprofen.
* Any current or prior receipt of LA parenteral ARVs such as mAbs targeting HIV-1, injectable CAB, or injectable RPV, for treatment or prophylaxis (PrEP, PEP).
Substudy-01, Substudy-02, Substudy-03:
* Requirement for ongoing therapy with any prohibited medications listed in protocol.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/10/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
18/03/2024
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Sample size
Target
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Accrual to date
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Final
49
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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0
United States of America
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State/province [1]
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California
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Country [2]
0
0
United States of America
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State/province [2]
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Connecticut
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Country [3]
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0
United States of America
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State/province [3]
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District of Columbia
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Country [4]
0
0
United States of America
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State/province [4]
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Florida
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Country [5]
0
0
United States of America
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State/province [5]
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Georgia
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Country [6]
0
0
United States of America
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State/province [6]
0
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Indiana
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Country [7]
0
0
United States of America
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State/province [7]
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0
Ohio
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Country [8]
0
0
United States of America
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State/province [8]
0
0
Texas
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Country [9]
0
0
United States of America
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State/province [9]
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0
Washington
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Country [10]
0
0
Dominican Republic
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State/province [10]
0
0
Santo Domingo
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Country [11]
0
0
Thailand
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State/province [11]
0
0
Bangkok
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Country [12]
0
0
Thailand
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State/province [12]
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0
Khon Kaen
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Gilead Sciences
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
Master protocol: The goal of this master clinical trial study is to learn how novel antiretrovirals (medicines that stop the virus from multiplying) affect the human immunodeficiency virus-1 (HIV-1) infection in people living with HIV (PWH). Substudy-01 (GS-US-544-5905-01) will evaluate bavtavirine in PWH. Substudy-02 (GS-US-544-5905-02) will evaluate GS-1720 in PWH. Substudy-03 (GS-US-544-5905-03) will evaluate GS-6212 in PWH.
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Trial website
https://clinicaltrials.gov/study/NCT05585307
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Trial related presentations / publications
Carl J. Fichtenbaum, Mezgebe Berhe, Jose Bordon, et al, Antiviral Activity, Safety, and Pharmacokinetics of GS-1720: A Novel Weekly Oral INSTI. Conference on Retroviruses and Opportunistic Infections, 2024, 3-6 March.
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Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed
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Contacts
Principal investigator
Name
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Gilead Study Director
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Address
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0
Gilead Sciences
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Country
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0
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Phone
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0
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Fax
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0
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Email
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0
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Contact person for public queries
Name
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Address
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0
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Country
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Phone
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Fax
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0
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Email
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0
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
Study Protocol: Substudy 01 Protocol Amendment 01
https://cdn.clinicaltrials.gov/large-docs/07/NCT05585307/Prot_000.pdf
Study protocol
Study Protocol: Substudy 02 Protocol Amendment 02
https://cdn.clinicaltrials.gov/large-docs/07/NCT05585307/Prot_001.pdf
Study protocol
Study Protocol: Substudy 03 Protocol Amendment 01
https://cdn.clinicaltrials.gov/large-docs/07/NCT05585307/Prot_002.pdf
Statistical analysis plan
Statistical Analysis Plan: Substudy 01 Statistical...
[
More Details
]
https://cdn.clinicaltrials.gov/large-docs/07/NCT05585307/SAP_003.pdf
Statistical analysis plan
Statistical Analysis Plan: Substudy 02 Statistical...
[
More Details
]
https://cdn.clinicaltrials.gov/large-docs/07/NCT05585307/SAP_004.pdf
Statistical analysis plan
Statistical Analysis Plan: Substudy 03 Statistical...
[
More Details
]
https://cdn.clinicaltrials.gov/large-docs/07/NCT05585307/SAP_005.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT05585307
Download to PDF