A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
This is a phase 1/2 study in which healthy adult subjects and subjects with chronic hepatitis B virus (HBV) infection will receive VIR-2218 or placebo and will be assessed for safety, tolerability, pharmacokinetics, and antiviral activity (only in subjects with chronic HBV).
In the single ascending dose (SAD) part, Part A, healthy adult subjects will receive one dose of VIR-2218 or placebo, administered subcutaneously (SC). In the multiple ascending dose (MAD) parts, Part B & Part C, subjects with chronic HBV infection will receive two doses of VIR-2218 or placebo every 4 weeks administered SC.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 是
入选标准
- •Male or female age 18 - 55
- •BMI 18 - 32 kg/m^2
排除标准
- •Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
- •History or evidence of drug or alcohol abuse
- •History of intolerance to SC injection
- •Parts B/C MAD:
- •Inclusion Criteria:
- •Male or female age 18 - 65
- •BMI 18 - 32 kg/m^2
- •Chronic HBV infection for >/= 6 months
- •Exclusion Criteria:
- •Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
- •Significant fibrosis or cirrhosis
- •History or evidence of drug or alcohol abuse
- •History of intolerance to SC injection
- •History of chronic liver disease from any cause other than chronic HBV infection
- •History of hepatic decompensation
研究组 & 干预措施
Part A: SAD Placebo
Healthy subjects received a single dose of placebo administered SC
干预措施: Placebo (Drug)
Part A: SAD VIR-2218 50 mg
Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC
干预措施: VIR-2218 (Drug)
Part A: SAD VIR-2218 100 mg
Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC
干预措施: VIR-2218 (Drug)
Part A: SAD VIR-2218 200 mg
Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC
干预措施: VIR-2218 (Drug)
Part A: SAD VIR-2218 400 mg
Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC
干预措施: VIR-2218 (Drug)
Part A: SAD VIR-2218 600 mg
Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC
干预措施: VIR-2218 (Drug)
Part A: SAD VIR-2218 900 mg
Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC
干预措施: VIR-2218 (Drug)
Part B: MAD VIR-2218 20 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.
干预措施: VIR-2218 (Drug)
Part B: MAD VIR-2218 50 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
干预措施: VIR-2218 (Drug)
Part B: MAD VIR-2218 100 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.
干预措施: VIR-2218 (Drug)
Part B: MAD VIR-2218 200 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
干预措施: VIR-2218 (Drug)
Part C: MAD VIR-2218 50 mg
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
干预措施: VIR-2218 (Drug)
Part C: MAD VIR-2218 200 mg
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
干预措施: VIR-2218 (Drug)
Part B: MAD Placebo
Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.
干预措施: Placebo (Drug)
Part C: MAD Placebo
Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: Up to 364 days
Number of Subjects with Adverse Events as assessed by CTCAE v5.0. In our planned analysis for this outcome measure, incidence is defined as the number of participants with treatment emergent AEs (TEAEs) in relation to the total number of participants in the cohort.
Clinical Assessments Including But Not Limited to Laboratory Test Results
时间窗: Up to 336 days
Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.
次要结局
- Maximum Plasma Concentration (ng/mL)(Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5)
- Time to Reach Maximum Plasma Concentration (h)(Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5)
- Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)(Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5)
- Apparent Terminal Elimination Half-life (h)(Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1)
- Apparent Plasma Clearance (L/h)(Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1)
- Apparent Volume of Distribution (L)(Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1)
- Urine %fe 0-24h(Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs))
- Apparent Renal Clearance (CLR/F)(Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs))
- Maximum Reduction of Serum HBsAg From Baseline(Up to 112 days)
- Number of Subjects With Serum HBsAg Loss at Any Time Point(Up to 336 days)
- Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months(Up to 336 days)
- Number of Subjects With Anti-HBs Seroconversion at Any Timepoint(Up to 336 days)
- Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint(Up to 336 days)