Study of Novel Antiretrovirals in Participants With HIV-1

• ClinicalTrials.gov Identifier: NCT05585307
• Recruitment Status: Recruiting
• First Posted: October 18, 2022
• Last Update Posted: January 17, 2023
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

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
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.

Study Design

• 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

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 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)

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 [ 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 ]

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

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

Locations

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

• Study Director: Gilead Study Director; Gilead Sciences

More Information

Additional Information:

Gilead Clinical Trials Website 

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT05585307
• Other Study ID Numbers: GS-US-544-5905
• First Posted: October 18, 2022
• Last Update Posted: January 17, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No