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Study of Novel Antiretrovirals in Participants With HIV-1

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05585307
Recruitment Status : Recruiting
First Posted : October 18, 2022
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

Master protocol: The goal of this master (umbrella) clinical trial study is to learn how novel antiretrovirals affect the HIV-1 infection in people living with HIV (PWH). The safety and how well the study drugs are tolerated will be determined by using physical exams, laboratory tests, and any symptoms or problems a participant might experience during the study.

Substudy-01 (GS-US-544-5905-01) will evaluate GS-5894 in people with HIV PWH.


Condition or disease Intervention/treatment Phase
HIV-1-infection Drug: GS-5894 Drug: B/F/TAF Drug: Standard of Care Phase 1

Detailed Description:

This umbrella study will begin with a substudy of GS-5894 (Substudy-01), and new substudies may be added in the future. Substudies evaluating additional study drugs will be added in a staggered manner when relevant nonclinical and/or clinical data become available.

  • Substudy-01 planned enrollment is 30.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 26, 2022
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Substudy-01: GS-5894

Participants will receive GS-5894. After assessments on Day 11 or upon early termination (ET), participants will initiate a regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), or other non-nonnucleoside reverse transcriptase inhibitor (NNRTI) based standard of care (SOC) antiretroviral (ART) regimen up to Day 39.

Non-NNRTI SOC ART regimen may include:

  • abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC), (ABC/DTG/3TC)
  • DTG plus (tenofovir alafenamide fumarate (TAF) or tenofovir disoproxil fumarate (TDF)) plus (emtricitabine (FTC) or 3TC)

Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.

Drug: GS-5894
Administered orally

Drug: B/F/TAF
Administered orally
Other Name: Biktarvy®

Drug: Standard of Care

Antiretroviral therapy, administered orally

Non-Nucleosite Reverse Transcriptase Inhibitors:

  • ABC/DTG/3TC
  • DTG plus (TAF or TDF) plus (FTC or 3TC)




Primary Outcome Measures :
  1. All Substudies: Change From Baseline in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (log10 copies/mL) at Day 11 [ Time Frame: Baseline; Day 11 ]

Secondary Outcome Measures :
  1. All Substudies: Change From Baseline in Plasma HIV-1 RNA (log10 copies/mL) at Day 8 [ Time Frame: Baseline; Day 8 ]
  2. All Substudies: Percentage of Participants Experiencing Adverse Events (AEs) [ Time Frame: First dose date up to Day 39 ]
  3. All Substudies: Percentage of Participants Experiencing Graded Laboratory Abnormalities [ Time Frame: First dose date up to Day 39 ]
  4. Substudy-01: Pharmacokinetic (PK) Parameter: Cmax of GS-5894 [ Time Frame: Day 1 Predose up to Day 11 ]
    Cmax is defined as the maximum observed concentration of drug.

  5. Substudy-01: PK Parameter of: AUC of GS-5894 [ Time Frame: Day 1 Predose up to Day 39 ]
    AUC is defined as the area under the concentration versus time curve.

  6. Substudy-01: PK Parameter: Ct of GS-5894 [ Time Frame: Day 1 Predose up to Day 11 ]
    Ct is defined as the concentration at specified time "t".

  7. All Substudies: Correlation Between Ct and/or AUC versus the Reduction of Plasma HIV-1 RNA (Log10 Copies/mL) from Day 1 Through Day 11 [ Time Frame: Day 1 up to Day 11 ]
  8. All Substudies: Percentage of Participants at Any Measurement Achieving HIV-1 RNA < 50 Copies/mL by Day 11 at Each Dose Level [ Time Frame: Up to Day 11 ]
  9. Substudy-01: Percentage of Participants with Emergence of Viral Resistance to Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) [ Time Frame: Up to Day 11 ]


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:

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/1.73m^2)
  • No clinically significant abnormalities in electrocardiogram (ECG) at screening.

Substudy-01:

  • Willing to initiate an standard of care (SOC) ART regimen on Day 11 or upon early termination (ET) as stated in the master protocol. For this substudy, willing to initiate bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®) (BVY) provided by the sponsor or a non-NNRTI-based SOC ART regimen selected by the investigator on Day 11 or upon ET.
  • Willing and able to comply with meal requirements on dosing days.

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:

  • Requirement for ongoing therapy with any prohibited medications listed in protocol.

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): NCT05585307


Contacts
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Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com

Locations
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United States, California
Ruane Clinical Research Group Recruiting
Los Angeles, California, United States, 90036
Mills Clinical Research Recruiting
Los Angeles, California, United States, 90069
Quest Clinical Research Recruiting
San Francisco, California, United States, 94115
United States, Florida
Gary J. Richmond, M.D.,P.A. Recruiting
Fort Lauderdale, Florida, United States, 33316
Midway Immunology and Research Center Recruiting
Fort Pierce, Florida, United States, 34982
AIDS Healthcare Foundation - South Beach Recruiting
Miami Beach, Florida, United States, 33140
Orlando Immunology Center Recruiting
Orlando, Florida, United States, 32803
Triple O Research Institute, P.A. Recruiting
West Palm Beach, Florida, United States, 33407
United States, Georgia
Infectious Disease Specialists of Atlanta Recruiting
Decatur, Georgia, United States, 30033
United States, Illinois
Howard Brown Health Center Recruiting
Chicago, Illinois, United States, 60613
United States, Michigan
Be Well Medical Center Recruiting
Berkley, Michigan, United States, 48072
United States, Texas
Central Texas Clinical Research Recruiting
Austin, Texas, United States, 78705
St. Hope Foundation, Inc. Recruiting
Bellaire, Texas, United States, 77401
Prism Health North Texas Recruiting
Dallas, Texas, United States, 75208
North Texas Infectious Diseases Consultants, P.A. Recruiting
Dallas, Texas, United States, 75246
The Crofoot Research Center, Inc. Recruiting
Houston, Texas, United States, 77098
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
Additional Information:
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT05585307    
Other Study ID Numbers: GS-US-544-5905
First Posted: October 18, 2022    Key Record Dates
Last Update Posted: January 17, 2023
Last Verified: January 2023
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