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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

Titles & IDs
Public title
Study of Novel Antiretrovirals in Participants With HIV-1
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
Secondary ID [1] 0 0
GS-US-544-5905
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV-1-infection 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline, Day 11
Secondary outcome [1] 0 0
Substudies 01, 02 and 03: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data
Timepoint [1] 0 0
Baseline, Day 8
Secondary outcome [2] 0 0
Substudies 01, 02 and 03: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)
Secondary outcome [3] 0 0
Substudies 01, 02 and 03: Percentage of Participants With Graded Laboratory Abnormalities
Timepoint [3] 0 0
First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)
Secondary outcome [4] 0 0
Substudy 01: Pharmacokinetic (PK) Parameter: Cmax of Bavtavirine
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Substudy 01: PK Parameter: AUC of Bavtavirine
Timepoint [5] 0 0
Day 1 up to Day 11
Secondary outcome [6] 0 0
Substudy 01: PK Parameter: Plasma Concentration of Bavtavirine
Timepoint [6] 0 0
Days 8 and 11
Secondary outcome [7] 0 0
Substudy 02: PK Parameter: Cmax of GS-1720
Timepoint [7] 0 0
Days 1 and 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and (optional) 12 hours postdose
Secondary outcome [8] 0 0
Substudy 02: PK Parameter: AUC of GS-1720
Timepoint [8] 0 0
Day 1 up to Day 11
Secondary outcome [9] 0 0
Substudy 02: PK Parameter: Plasma Concentration of GS-1720
Timepoint [9] 0 0
Days 8 and 11
Secondary outcome [10] 0 0
Substudy 03: PK Parameter: Cmax of GS-6212
Timepoint [10] 0 0
Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)
Secondary outcome [11] 0 0
Substudy 03: PK Parameter: AUC0-8h of GS-6212
Timepoint [11] 0 0
Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)
Secondary outcome [12] 0 0
Substudy 03: PK Parameter: AUCtau of GS-6212
Timepoint [12] 0 0
Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)
Secondary outcome [13] 0 0
Substudy 03: PK Parameter: Plasma Concentration of GS-6212
Timepoint [13] 0 0
Days 1 and 10: 8 hours postdose
Secondary outcome [14] 0 0
Substudy 03: PK Parameter: Ctrough of GS-6212 (Day 10)
Timepoint [14] 0 0
Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)
Secondary outcome [15] 0 0
Substudy 03: PK Parameter: Cavg of GS-6212 (Day 10)
Timepoint [15] 0 0
Day 10 (predose to 8 hours postdose)
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
Up to Day 11
Secondary outcome [17] 0 0
Substudies 01, 02 and 03: Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug
Timepoint [17] 0 0
Up to Day 11
Secondary outcome [18] 0 0
Substudy 01: Maximum Inhibitory Quotient (IQ) of Bavtavirine by Mean Plasma Concentration (Ct) up to Day 11
Timepoint [18] 0 0
Up to Day 11
Secondary outcome [19] 0 0
Substudy 02: Inhibitory Quotient (IQ) of GS-1720 by Mean Plasma Concentration (Ct) at Day 11
Timepoint [19] 0 0
Day 11
Secondary outcome [20] 0 0
Substudy 03: Inhibitory Quotient (IQ) of GS-6212 by Ctrough at Day 11
Timepoint [20] 0 0
Day 11

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.

Key
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/10/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/03/2024
Sample size
Target
Accrual to date
Final
49
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Dominican Republic
State/province [10] 0 0
Santo Domingo
Country [11] 0 0
Thailand
State/province [11] 0 0
Bangkok
Country [12] 0 0
Thailand
State/province [12] 0 0
Khon Kaen

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
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