An Umbrella Phase 1b, Open-label, Multi-Cohort Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1; Substudy-04: GS-1219
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 14
- 主要终点
- Change From Baseline in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (log10 Copies/mL) at Day 11 Relative to Historical Placebo Data
研究概览
简要总结
This study is part of a master study. The goal of master protocol (GSUS-544-5905, NCT05585307) 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 GS-US-544-5905-04 is to learn more about study drug GS-1219, safety, pharmacokinetics (PK) (how GS-1219 is absorbed, modified, distributed, and removed from the body of the participants), and antiviral activity in Participants With HIV-1.
详细描述
To refer master study protocol (GS-US-544-5905), refer to NCT05585307 on https://clinicaltrials.gov/
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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), injectable rilpivirine (RPV) or injectable Lenacapavir (LEN) 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-04:
- •Willing to initiate BVY provided by the sponsor, or an alternative SOC ART regimen selected by the investigator on Day 11 or upon ET.
- •Willing and able to comply with meal requirements on dosing days.
排除标准
- •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, or injectable LEN, for treatment or prophylaxis (PrEP, PEP).
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1 of GS-1219
Participants in Cohort 1 will receive a single dose of GS-1219 800 mg administered once daily on Day 1 through Day 4, followed by a single dose of GS-1219 800 mg administered on Day 7, all in the fasted condition.
After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®) (BVY), or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 25.
Following the completion of Cohort 1, additional cohorts may open for enrollment if further data are needed. Participants will receive single or multiple doses of GS-1219 up to 1800 mg administered in the fasted condition or with food (low-fat or high-fat meal).
干预措施: GS-1219 (Drug)
Cohort 1 of GS-1219
Participants in Cohort 1 will receive a single dose of GS-1219 800 mg administered once daily on Day 1 through Day 4, followed by a single dose of GS-1219 800 mg administered on Day 7, all in the fasted condition.
After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®) (BVY), or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 25.
Following the completion of Cohort 1, additional cohorts may open for enrollment if further data are needed. Participants will receive single or multiple doses of GS-1219 up to 1800 mg administered in the fasted condition or with food (low-fat or high-fat meal).
干预措施: BVY (Drug)
Cohort 1 of GS-1219
Participants in Cohort 1 will receive a single dose of GS-1219 800 mg administered once daily on Day 1 through Day 4, followed by a single dose of GS-1219 800 mg administered on Day 7, all in the fasted condition.
After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®) (BVY), or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 25.
Following the completion of Cohort 1, additional cohorts may open for enrollment if further data are needed. Participants will receive single or multiple doses of GS-1219 up to 1800 mg administered in the fasted condition or with food (low-fat or high-fat meal).
干预措施: Standard of Care (Drug)
结局指标
主要结局
Change From Baseline in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (log10 Copies/mL) at Day 11 Relative to Historical Placebo Data
时间窗: Baseline, Day 11
次要结局
- Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data(Baseline, Day 8)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(First dose up to Day 25)
- Percentage of Participants With Graded Laboratory Abnormalities(First dose up to Day 25)
- Pharmacokinetic (PK) Parameter: Cmax of GS-1219(Day 1 Predose up to Day 11)
- PK Parameter: AUC of GS-1219(Day 1 Predose up to Day 11)
- PK Parameter: Ct of GS-1219(Any day between Day 1 Predose up to Day 11)
- Percentage of Participants at Any Measurement Achieving HIV-1 RNA < 50 Copies/mL by Day 11 at Each Dose Level(Up to Day 11)
- Correlation Between Ct and/ or AUC versus the Change in Plasma HIV-1 RNA (Log10 Copies/mL) from Day 1 Through Day 11(Day 1 up to Day 11)
- Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug (GS-1219)(Up to Day 11)