A Phase 2/3, Open-Label Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1
概览
- 阶段
- 2 期
- 干预措施
- Lenacapavir
- 疾病 / 适应症
- HIV-1-infection
- 发起方
- Gilead Sciences
- 入组人数
- 75
- 试验地点
- 41
- 主要终点
- PK Parameter: Cmax of BIC and LEN at Steady State
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
The goal of this clinical study is to learn about the safety and tolerability of bictegravir/lenacapavir (BIC/LEN) and to learn how the study drug interacts with the body in virologically suppressed (VS) children and adolescents with human immunodeficiency virus type 1 (HIV-1) on a stable and complex antiretroviral (ARV) regimen. The study will also assess the safe loading dose of LEN and pharmacokinetics (PK) of BIC/LEN.
The primary objectives of this study are:
- To evaluate the steady-state PK of BIC and LEN and confirm the dose of the LEN loading dose and BIC/LEN FDC in VS children and adolescents with HIV-1.
- To evaluate the safety and tolerability of BIC/LEN through Week 24 in VS children and adolescents with HIV-1.
研究者
入排标准
入选标准
- •Age and body weight at screening:
- •Cohort 1: ≥ 12 years to \< 18 years weighing ≥ 35 kg.
- •Cohort 2: ≥ 6 years to \< 12 years weighing ≥ 25 kg to \< 35 kg.
- •Cohort 3: ≥ 2 years to \< 6 years weighing ≥ 10 kg to \< 25 kg.
- •On a complex ARV regimen. Complex regimens are any ARV therapy that is not a single-tablet regimen taken once daily (eg, \> 1 tablet or any other formulation a day).
- •Documented plasma HIV-1 ribonucleic acid (RNA) levels must be \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \< 50 copies/mL) in the last 6 months prior to screening (at least 1 measure prior to screening).
- •Plasma HIV-1 RNA levels \< 50 copies/mL at screening.
- •No documented or suspected resistance to integrase strand transfer inhibitors (mutations T66A/I/K, E92G/Q/V, G118R, F121C/Y, G140R, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
- •The following laboratory parameters at screening:
- •Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 using the Bedside Schwartz formula.
排除标准
- •CD4 cell count \< 200 cells/mm\^
- •CD4 percentage \< 20%.
- •Life expectancy ≤ 1 year.
- •An opportunistic illness indicative of Stage 3 HIV diagnosed within the 30 days prior to screening.
- •Evidence of active pulmonary or extrapulmonary tuberculosis within 3 months prior to screening.
- •Acute hepatitis within 30 days prior to screening.
- •Positive hepatitis C virus (HCV) antibody with detectable HCV RNA (participants positive for HCV antibody will have an HCV RNA test performed).
- •Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B virus (HBV) core antibody (antibody against hepatitis B core antigen \[anti-HBc\]) at screening. If a participant is negative for HBsAg and positive for anti-HBc but HBV DNA is undetectable, the participant may be enrolled.
- •A history of or current decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).Current alcohol or substance use judged by the investigator to potentially interfere with the participant's study compliance.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN 75/50 mg FDC
Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN 75/50 mg starting on Day 1 through Week 48. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
干预措施: Lenacapavir
Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN 75/50 mg FDC
Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN 75/50 mg starting on Day 1 through Week 48. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
干预措施: BIC/LEN FDC
Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 2 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
干预措施: Lenacapavir
Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 2 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
干预措施: BIC/LEN FDC
Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 3 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
干预措施: Lenacapavir
Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 3 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period.
干预措施: BIC/LEN FDC
结局指标
主要结局
PK Parameter: Cmax of BIC and LEN at Steady State
时间窗: Day 1 up to Week 24, as appropriate
Cmax is defined as the maximum observed concentration of drug at steady state.
PK Parameter: AUCtau of BIC and LEN at Steady State
时间窗: Day 1 up to Week 24, as appropriate
AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state.
PK Parameter: Ctrough of BIC and LEN at Steady State
时间窗: Day 1 up to Week 24, as appropriate
Ctrough is defined as the observed drug concentration at the end of the dosing interval at steady state.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Through Week 24
时间窗: First dose date up to Week 24
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24
时间窗: First dose date up to Week 24
次要结局
- PK Parameter: Vz for BIC and LEN at Steady State(Day 1 up to Week 48, as appropriate)
- PK Parameter: λz for BIC and LEN at Steady State(Day 1 up to Week 48, as appropriate)
- Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48(First does date up to Week 48)
- Proportion of Participants With Plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Week 48 Based on the United States FDA-Defined Snapshot Algorithm(Week 48)
- PK Parameter: Tlast for BIC and LEN at Steady State(Day 1 up to Week 48, as appropriate)
- PK Parameter: CL for BIC and LEN at Steady State(Day 1 up to Week 48, as appropriate)
- Percentage of Participants Experiencing TEAEs Through Week 48(First dose date up to Week 48)
- Change from Baseline in Clusters of Differentiation 4 (CD4) Cell Counts at Week 24(Baseline, Week 24)
- Change from Baseline in CD4 Cell Counts at Week 48(Baseline, Week 48)
- Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire(Week 4)
- Proportion of Participants With Plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Week 24 Based on the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm(Week 24)
- Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire(Day 2)
- Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire(Day 1)
- PK Parameter: AUClast for BIC and LEN at Steady State(Day 1 up to Week 48, as appropriate)
- PK Parameter: T1/2 for BIC and LEN at Steady State(Day 1 up to Week 48, as appropriate)
- PK Parameter: Tmax for BIC and LEN at Steady State(Day 1 up to Week 48, as appropriate)
- Change from Baseline in CD4 Percentage at Week 24(Baseline, Week 24)
- Change from Baseline in CD4 Percentage at Week 48(Baseline, Week 48)
- Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire(Week 24)
- Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire(Week 48)
- Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire(Day 1)