HIV-1-infection Clinical Trial
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
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.
| Status | Recruiting |
| Enrollment | 110 |
| Est. completion date | December 2024 |
| Est. primary completion date | December 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility | 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/1.73 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 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. |
| Country | Name | City | State |
|---|---|---|---|
| Dominican Republic | Instituto Dominicano de Estudio Virologicos - IDEV,Substudy-02 | Santo Domingo | |
| Thailand | Faculty of Medicine Ramathibodi Hospital, Mahidol University,Substudy-02 | Bangkok | |
| Thailand | The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-02 | Bangkok | |
| Thailand | The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-03 | Bangkok | |
| Thailand | Faculty of Medicine, Srinagarind Hospital, Khon Kaen University,Substudy-03 | Khon Kaen | |
| United States | Atlanta ID Group, PC,Substudy-01 | Atlanta | Georgia |
| United States | Atlanta ID Group, PC,Substudy-02 | Atlanta | Georgia |
| United States | Central Texas Clinical Research,Substudy-01 | Austin | Texas |
| United States | Central Texas Clinical Research,Substudy-02 | Austin | Texas |
| United States | Central Texas Clinical Research,Substudy-03 | Austin | Texas |
| United States | St Hope Foundation Inc.,Substudy-02 | Bellaire | Texas |
| United States | St. Hope Foundation, Inc.,Substudy-01 | Bellaire | Texas |
| United States | Be Well Medical Center,Substudy-01 | Berkley | Michigan |
| United States | Be Well Medical Center,Substudy-02 | Berkley | Michigan |
| United States | Howard Brown Health Center,Substudy-01 | Chicago | Illinois |
| United States | Howard Brown Health Center,Substudy-02 | Chicago | Illinois |
| United States | University of Cincinnati College of Medicine,Substudy-01 | Cincinnati | Ohio |
| United States | University of Cincinnati College of Medicine,Substudy-02 | Cincinnati | Ohio |
| United States | University of Cincinnati College of Medicine,Substudy-03 | Cincinnati | Ohio |
| United States | North Texas Infectious Diseases Consultant, P.A.,Substudy-02 | Dallas | Texas |
| United States | North Texas Infectious Diseases Consultants, P.A.,Substudy-01 | Dallas | Texas |
| United States | North Texas Infectious Diseases Consultants, P.A.,Substudy-03 | Dallas | Texas |
| United States | Prism Health North Texas,Substudy-01 | Dallas | Texas |
| United States | Prism Health North Texas,Substudy-02 | Dallas | Texas |
| United States | Prism Health North Texas,Substudy-03 | Dallas | Texas |
| United States | Infectious Disease Specialists of Atlanta,Substudy-01 | Decatur | Georgia |
| United States | Infectious Disease Specialists of Atlanta,Substudy-02 | Decatur | Georgia |
| United States | Infectious Disease Specialists of Atlanta,Substudy-03 | Decatur | Georgia |
| United States | Midland Florida Clinical Research Center, LLC,Substudy-01 | DeLand | Florida |
| United States | Midland Florida Clinical Research Center, LLC,Substudy-02 | DeLand | Florida |
| United States | Midland Florida Clinical Research, LLC,Substudy-03 | DeLand | Florida |
| United States | AXCES Research,Substudy-01 | El Paso | Texas |
| United States | AXCES Research,Substudy-02 | El Paso | Texas |
| United States | AXES Research Group LLC,Substudy-03 | El Paso | Texas |
| United States | CAN Community Health Care, Inc.,Substudy-02 | Fort Lauderdale | Florida |
| United States | Gary J. Richmond, M.D.,P.A.,Substudy-01 | Fort Lauderdale | Florida |
| United States | Therafirst Medical Center,Substudy-01 | Fort Lauderdale | Florida |
| United States | Therafirst Medical Center,Substudy-02 | Fort Lauderdale | Florida |
| United States | Midway Immunology and Research Center,Substudy-01 | Fort Pierce | Florida |
| United States | Midway Immunology and Research Center,Substudy-02 | Fort Pierce | Florida |
| United States | Midway Immunology and Research Center,Substudy-03 | Fort Pierce | Florida |
| United States | Northwell Health,Substudy-02 | Great Neck | New York |
| United States | Northwell Health,Substudy-03 | Great Neck | New York |
| United States | The Crofoot Research Center, Inc.,Substudy-01 | Houston | Texas |
| United States | The Crofoot Research, INC,Substudy-02 | Houston | Texas |
| United States | The Crofoot Research, INC,Substudy-03 | Houston | Texas |
| United States | Therapeutic Concepts, PA,Substudy-01 | Houston | Texas |
| United States | Therapeutic Concepts, PA,Substudy-02 | Houston | Texas |
| United States | Therapeutic Concepts, PA,Substudy-03 | Houston | Texas |
| United States | Indiana CTSI Clinical Research Center,Substudy-01 | Indianapolis | Indiana |
| United States | Indiana CTSI Clinical Research Center,Substudy-02 | Indianapolis | Indiana |
| United States | Indiana CTSI Clinical Research Center,Substudy-03 | Indianapolis | Indiana |
| United States | KC CARE Health Center,Substudy-01 | Kansas City | Missouri |
| United States | KC CARE Health Center,Substudy-02 | Kansas City | Missouri |
| United States | Long Beach Education and Research Consultants,Substudy-01 | Long Beach | California |
| United States | Long Beach Education and Research Consultants,Substudy-02 | Long Beach | California |
| United States | Long Beach Education and Research Consultants,Substudy-03 | Long Beach | California |
| United States | Mills Clinical Research,Substudy-01 | Los Angeles | California |
| United States | Mills Clinical Research,Substudy-02 | Los Angeles | California |
| United States | Mills Clinical Research,Substudy-03 | Los Angeles | California |
| United States | Ruane Clinical Research Group,Substudy-01 | Los Angeles | California |
| United States | Ruane Clinical Research Group,Substudy-02 | Los Angeles | California |
| United States | Northwell Health,Substudy-01 | Manhasset | New York |
| United States | AIDS Healthcare Foundation - South Beach,Substudy-01 | Miami Beach | Florida |
| United States | AIDS Healthcare Foundation - South Beach,Substudy-02 | Miami Beach | Florida |
| United States | Yale University,Substudy-01 | New Haven | Connecticut |
| United States | Yale University,Substudy-02 | New Haven | Connecticut |
| United States | Yale University; School of Medicine; AIDS Program (Administrative & Study Supplies),Substudy-03 | New Haven | Connecticut |
| United States | Bliss Health,Substudy-01 | Orlando | Florida |
| United States | Bliss Health,Substudy-02 | Orlando | Florida |
| United States | Bliss Health,Substudy-03 | Orlando | Florida |
| United States | Orlando Immunology Center,Substudy-01 | Orlando | Florida |
| United States | Orlando Immunology Center,Substudy-02 | Orlando | Florida |
| United States | Orlando Immunology Center,Substudy-03 | Orlando | Florida |
| United States | BIOS Clinical Research,Substudy-01 | Palm Springs | California |
| United States | Bios Clinical Research,Substudy-02 | Palm Springs | California |
| United States | BIOS Clinical Research,Substudy-03 | Palm Springs | California |
| United States | Quest Clinical Research,Substudy-01 | San Francisco | California |
| United States | Quest Clinical Research,Substudy-02 | San Francisco | California |
| United States | Quest Clinical Research,Substudy-03 | San Francisco | California |
| United States | CAN Community Health,Substudy-01 | Sarasota | Florida |
| United States | Can Community Health,Substudy-02 | Sarasota | Florida |
| United States | Chatham County Health Department,Substudy-01 | Savannah | Georgia |
| United States | Chatham County Health Department,Substudy-02 | Savannah | Georgia |
| United States | Chatham County Health Department,Substudy-03 | Savannah | Georgia |
| United States | Seattle Infectious Disease Clinic,Substudy-01 | Seattle | Washington |
| United States | Seattle Infectious Disease Clinic,Substudy-02 | Seattle | Washington |
| United States | MultiCare Rockwood Main Clinic - Research,Substudy-01 | Spokane | Washington |
| United States | MultiCare Rockwood Main Clinic - Research,Substudy-02 | Spokane | Washington |
| United States | MultiCare Rockwood Main Clinic- Research,Substudy-03 | Spokane | Washington |
| United States | Washington Health Institute,Substudy-01 | Washington | District of Columbia |
| United States | Washington Health Institute,Substudy-02 | Washington | District of Columbia |
| United States | Washington Health Institute,Substudy-03 | Washington | District of Columbia |
| United States | Triple O Research Institute, P.A.,Substudy-01 | West Palm Beach | Florida |
| United States | Triple O Research Institute, P.A.,Substudy-02 | West Palm Beach | Florida |
| United States | Triple O Research Institute, P.A.,Substudy-03 | West Palm Beach | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Gilead Sciences |
United States, Dominican Republic, Thailand,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | All Substudies: Change From Baseline in Plasma HIV-1 RNA (log10 copies/mL) at Day 8 | Baseline; Day 8 | ||
| Secondary | All Substudies: Percentage of Participants Experiencing Adverse Events (AEs) | Substudy-01: First dose date up to Day 39; Substudy-02: First dose date up to Day 60; Substudy-03 First dose date up to Day 25 | ||
| Secondary | All Substudies: Percentage of Participants Experiencing Graded Laboratory Abnormalities | Substudy-01: First dose date up to Day 39; Substudy-02: First dose date and up to Day 60; Substudy-03 First dose date up to Day 25 | ||
| Secondary | Substudy-01, Substudy-02, and Substudy-03: Pharmacokinetic (PK) Parameter: Cmax of bavtavirine, GS-1720, and GS-6212 | Cmax is defined as the maximum observed concentration of drug. | Day 1 Predose up to Day 11 | |
| Secondary | Substudy-01, Substudy-02, and Substudy-03: PK Parameter of: AUC of bavtavirine, GS-1720, and GS-6212 | AUC is defined as the area under the concentration versus time curve. | Substudy-01: Day 1 Predose up to Day 39; Substudy-02: Day 1 Predose up to Day 60 | |
| Secondary | Substudy-01, Substudy-02, and Substudy-03: PK Parameter: Ct of bavtavirine, GS-1720, and GS-6212 | Ct is defined as the concentration at specified time "t". | Day 1 Predose up to Day 11 | |
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | Percentage of Participants with Emergence of Viral Resistance to the ARV Class of the Given Drug | The ARV class of given drugs would be BVY or NNRTIs (Substudy 01) or INSTIs (Substudy 02) or INSTIs (Substudy 03). | Up to Day 11 |
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