A Phase 2 Randomized, Open-Label, Active-Controlled Study Evaluating the Safety and Efficacy of an Oral Weekly Regimen of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 142
- 试验地点
- 44
- 主要终点
- Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of oral weekly islatravir (ISL) in combination with lenacapavir (LEN) in virologically suppressed people with HIV (PWH) at Week 24.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for ≥ 24 weeks at screening.
- •Documented plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) < 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) for ≥ 24 weeks before and at screening.
- •Plasma HIV-1 RNA < 50 copies/mL at screening.
排除标准
- •History of prior virologic failure while receiving treatment for HIV-
- •Prior use of, or exposure to, islatravir (ISL) or lenacapavir (LEN).
- •Active, serious infections requiring parenteral therapy < 30 days before randomization.
- •Active or occult hepatitis B virus (HBV) coinfection, defined as hepatitis B core antibody (HBcAb) positive, hepatitis B surface antigen (HBsAg) positive, or HBV deoxyribonucleic acid (DNA) positive as determined by the central laboratory.
- •Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA.
- •Any of the following laboratory values at screening:
- •Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
- •CD4+ T-cells < 200 cells/mm^3 (Cohort 1); CD4+ T-cells < 350 cells/mm^3 (cohort 2).
- •Absolute lymphocyte count < 900 cells/mm^3 (cohort 2).
- •Individuals of childbearing potential (as defined in protocol) who have a positive serum pregnancy test at screening or positive urine and serum pregnancy tests at Day 1 prior to study drug administration.
- •Individuals who plan to continue breastfeeding during the study.
- •Documented historical or screening resistance reports showing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) resistance mutations in reverse transcriptase, including M184V/I (Cohort 2).
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1 (ISL+LEN)
Participants will receive the following for at least 48 weeks:
- Day 1 and Day 2: ISL 40 and LEN 600 mg
- Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg
干预措施: ISL (Drug)
Cohort 1 (ISL+LEN)
Participants will receive the following for at least 48 weeks:
- Day 1 and Day 2: ISL 40 and LEN 600 mg
- Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg
干预措施: LEN (Drug)
Cohort 1 (B/F/TAF to ISL+LEN)
Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks
After 48 weeks, participants will switch from B/F/TAF to ISL+LEN
- ISL 40 and LEN 600 mg on Day 1 and Day 2
- ISL 20 mg and LEN 300 mg weekly
Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.
干预措施: ISL (Drug)
Cohort 1 (B/F/TAF to ISL+LEN)
Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks
After 48 weeks, participants will switch from B/F/TAF to ISL+LEN
- ISL 40 and LEN 600 mg on Day 1 and Day 2
- ISL 20 mg and LEN 300 mg weekly
Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.
干预措施: LEN (Drug)
Cohort 1 (B/F/TAF to ISL+LEN)
Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks
After 48 weeks, participants will switch from B/F/TAF to ISL+LEN
- ISL 40 and LEN 600 mg on Day 1 and Day 2
- ISL 20 mg and LEN 300 mg weekly
Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.
干预措施: B/F/TAF (Drug)
Cohort 2 (ISL+LEN)
Participants will receive the following for at least 48 weeks
- Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg)
- Day 2: LEN only oral 600 mg (2 x 300 mg)
- Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg
干预措施: ISL (Drug)
Cohort 2 (ISL+LEN)
Participants will receive the following for at least 48 weeks
- Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg)
- Day 2: LEN only oral 600 mg (2 x 300 mg)
- Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg
干预措施: LEN (Drug)
Cohort 2 (B/F/TAF to ISL+LEN)
Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.
干预措施: ISL (Drug)
Cohort 2 (B/F/TAF to ISL+LEN)
Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.
干预措施: LEN (Drug)
Cohort 2 (B/F/TAF to ISL+LEN)
Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.
干预措施: B/F/TAF (Drug)
Extension Phase Cohort 2 of ISL/LEN Fixed Dose Combination (FDC)
After 48 Weeks of randomized treatment, all participants will be given an option to participate in an Extension Phase to receive ISL+LEN or ISL/LEN FDC tablet (when available) until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first.
Participants receiving ISL+LEN during the randomized phase will continue to take ISL + LEN weekly.
Participants receiving B/F/TAF during the randomized phase will switch to ISL+LEN:
- Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg)
- Day 2: LEN only oral 600 mg (2 x 300 mg)
- Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg
Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.
All participants in the extension phase will be transitioned to weekly ISL/LEN FDC (Dose A) tablet when it becomes available.
干预措施: ISL/LEN FDC (Drug)
结局指标
主要结局
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm
时间窗: Week 24
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.
次要结局
- Change From Baseline in CD4+ Cell Count at Week 48(Baseline and Week 48)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation(Up to 5 years)
- Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm(Week 12)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm(Week 12)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm(Week 48)
- Change From Baseline in CD4+ Cell Count at Week 24(Baseline and Week 24)
- Cohort 1: Plasma Concentrations for ISL(Anytime postdose at Week 4)
- Cohort 2: PK Parameter: AUCtau of ISL(Anytime post dose at either Week 12 or Week 18)
- Cohort 2: PK Parameter: Tmax of LEN(Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18)
- Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm(Week 48)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm(Week 24)
- Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12(Baseline and Week 12)
- Cohort 2: PK Parameter: Tmax of ISL(Anytime post dose on Day 1 and at either Week 12 or Week 18)
- Plasma Concentrations for LEN(Anytime postdose at Week 4)
- Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL)(Anytime post dose on Day 1 and at either Week 12 or Week 18)
- Cohort 2: PK Parameter: Ctau of ISL(Anytime post dose at either Week 12 or Week 18)
- Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN(Anytime post dose on Day 1, Day 2 and at either Week 12 or 18)
- Cohort 2: PK Parameter: Ctau of LEN(Anytime post dose at either Week 12 or Week 18)
- Cohort 2: PK Parameter: AUCtau of LEN(Anytime post dose at either Week 12 or Week 18)