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Study of Novel Antiretrovirals in Participants With HIV-1

Sponsor
Gilead Sciences (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05585307
Collaborator
(none)
110
Enrollment
16
Locations
1
Arm
19.2
Anticipated Duration (Months)
6.9
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Oct 26, 2022
Anticipated Primary Completion Date :
May 1, 2024
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

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 Names:
  • 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)

    Outcome Measures

    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 [Baseline; Day 11]

    Secondary Outcome Measures

    1. All Substudies: Change From Baseline in Plasma HIV-1 RNA (log10 copies/mL) at Day 8 [Baseline; Day 8]

    2. All Substudies: Percentage of Participants Experiencing Adverse Events (AEs) [First dose date up to Day 39]

    3. All Substudies: Percentage of Participants Experiencing Graded Laboratory Abnormalities [First dose date up to Day 39]

    4. Substudy-01: Pharmacokinetic (PK) Parameter: Cmax of GS-5894 [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 [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 [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 [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 [Up to Day 11]

    9. Substudy-01: Percentage of Participants with Emergence of Viral Resistance to Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) [Up to Day 11]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ruane Clinical Research Group Los Angeles California United States 90036
    2 Mills Clinical Research Los Angeles California United States 90069
    3 Quest Clinical Research San Francisco California United States 94115
    4 Gary J. Richmond, M.D.,P.A. Fort Lauderdale Florida United States 33316
    5 Midway Immunology and Research Center Fort Pierce Florida United States 34982
    6 AIDS Healthcare Foundation - South Beach Miami Beach Florida United States 33140
    7 Orlando Immunology Center Orlando Florida United States 32803
    8 Triple O Research Institute, P.A. West Palm Beach Florida United States 33407
    9 Infectious Disease Specialists of Atlanta Decatur Georgia United States 30033
    10 Howard Brown Health Center Chicago Illinois United States 60613
    11 Be Well Medical Center Berkley Michigan United States 48072
    12 Central Texas Clinical Research Austin Texas United States 78705
    13 St. Hope Foundation, Inc. Bellaire Texas United States 77401
    14 Prism Health North Texas Dallas Texas United States 75208
    15 North Texas Infectious Diseases Consultants, P.A. Dallas Texas United States 75246
    16 The Crofoot Research Center, Inc. Houston Texas United States 77098

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT05585307
    Other Study ID Numbers:
    • GS-US-544-5905
    First Posted:
    Oct 18, 2022
    Last Update Posted:
    Jan 17, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No

    Study Results

    No Results Posted as of Jan 17, 2023