A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of Cetrelimab (JNJ 63723283), an Anti-PD-1 Monoclonal Antibody, in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 13
- 主要终点
- Maximum Observed Serum Concentration (Cmax) of Cetrelimab
研究概览
简要总结
The purpose of the study is to characterize the pharmacokinetic (PK) profile of cetrelimab administered subcutaneous (SC) and optionally intravenous (IV) in chronic hepatitis B (CHB) participants.
详细描述
Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute (less than 6 months) or chronic (more than 6 months) infection. Persistence of HBV infection requires antigen-specific immune tolerance that prevents clearance of infected cells. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin (Ig) G4 kappa monoclonal antibody (mAb) that binds to programmed cell death receptor-1 (PD-1) with high affinity and specificity. PD-(L)1 inhibitors could possibly reverse the immune dysfunction from HBV. The study will be conducted in 3 phases: a screening phase (6 weeks), a single dose intervention phase (1 day), and a 24-week follow-up phase. The duration of individual participation will be up to 30 weeks. Key safety assessments include monitoring of Adverse Events (AEs), physical examination, vital signs, Electrocardiogram (ECGs), Injection site reaction (ISRs), Infusion-related reaction (IRRs), and clinical laboratory tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
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
- •Must have chronic hepatitis B virus (HBV) infection documented
- •Participants should be virologically suppressed, Hepatitis Be antigen (HBeAg) status (positive or negative) be on stable Nucleotide analog (NA) treatment for at least 6 months
- •Must have: a) A liver biopsy result classified as Metavir F0-F2 within 2 years prior to screening; b) If a liver biopsy result is not available: Fibroscan liver stiffness measurement less than or equal to (<=) to 9.0 kilopascals (kPa) within 6 months prior to screening or at the time of screening
- •Must be medically stable
- •Must have a body mass index (weight in kilogram [kg] divided by the square of height in meters) between 18.0 and 30.0 kilograms per meter square (kg/m^2), extremes included
- •Exclusion Criteria
- •History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices
- •Participants with evidence of liver disease of non-HBV etiology.
- •Participants with history or signs of cirrhosis or portal hypertension (nodules, no smooth liver contour, no normal portal vein, spleen size greater than or equal to [>=] 12 centimeters) or signs of hepatocellular carcinoma (HCC) on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening
- •History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
排除标准
- 未提供
研究组 & 干预措施
Cohort 1: Cetrelimab or Placebo (Dose 1)
Participants will receive cetrelimab Dose 1 or placebo via subcutaneous (SC) injection on Day 1.
干预措施: Cetrelimab (Drug)
Cohort 1: Cetrelimab or Placebo (Dose 1)
Participants will receive cetrelimab Dose 1 or placebo via subcutaneous (SC) injection on Day 1.
干预措施: Placebo (Drug)
Cohort 2 (Optional): Cetrelimab or Placebo (Dose 2)
Participants will receive cetrelimab Dose 2 or placebo administered via an Intravenous (IV) infusion on Day 1 based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as pharmacokinetic (PK) and receptor occupancy (RO) data through at least day 4 postdose).
干预措施: Cetrelimab (Drug)
Cohort 2 (Optional): Cetrelimab or Placebo (Dose 2)
Participants will receive cetrelimab Dose 2 or placebo administered via an Intravenous (IV) infusion on Day 1 based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as pharmacokinetic (PK) and receptor occupancy (RO) data through at least day 4 postdose).
干预措施: Placebo (Drug)
Cohort 3 (Optional): Cetrelimab or Placebo
Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose).
干预措施: Cetrelimab (Drug)
Cohort 3 (Optional): Cetrelimab or Placebo
Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohort(s) (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose).
干预措施: Placebo (Drug)
Cohort 4 (Optional): Cetrelimab or Placebo
Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohorts (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose).
干预措施: Cetrelimab (Drug)
Cohort 4 (Optional): Cetrelimab or Placebo
Participant will receive cetrelimab or placebo via SC injection based on the data review of previous cohorts (safety and tolerability data through at least 6 weeks postdose as well as PK and RO data through at least day 4 postdose).
干预措施: Placebo (Drug)
结局指标
主要结局
Maximum Observed Serum Concentration (Cmax) of Cetrelimab
时间窗: Up to 24 weeks
Cmax is defined as maximum observed serum concentration of cetrelimab.
Total Systemic Clearance of Cetrelimab
时间窗: Up to 24 weeks
Total systemic clearance is a quantitative measure of the rate at which cetrelimab is removed from the body.
Area Under the Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Cetrelimab
时间窗: Up to 24 weeks
AUC(0-last) is defined as area under the concentration-time curve from time 0 to the time of the last measurable concentration (non-below quantification limit \[non-BQL\]) of cetrelimab as calculated by linear-linear trapezoidal summation.
Apparent Terminal Elimination Half-life (t1/2) of Cetrelimab
时间窗: Up to 24 weeks
t1/2 is defined as apparent terminal elimination half-life of cetrelimab.
次要结局
- Change from Baseline in Hepatitis B Virus Deoxyribonucleic acid (HBV DNA) Levels Over Time(Baseline up to 30 weeks)
- Cohorts 1,3 and 4: Number of Participants with Injection Site Reaction (ISR)(Up to 30 weeks)
- Change from Baseline in HBsAg and HBeAg Levels Over Time(Baseline up to 30 weeks)
- Number of Participants with Adverse Events (AEs)(Up to 30 weeks)
- Number of Participants with Abnormalities in Clinical Laboratory Tests(Up to 30 weeks)