NCT03932513终止2 期
A Phase 2, Open-label Study Evaluating the Intra-hepatic Effect of Inarigivir 400 mg Per Day and 400 mg Three Times Per Week on Immune Response and Viral Markers in Virally Suppressed Patients With Chronic Hepatitis B Infection
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Change in intra-hepatic immune response
研究概览
简要总结
A single center, open-label, study to evaluate the intra-hepatic effect of inarigivir dose per day and three times per week on immune response and viral markers in virally suppressed patients with chronic hepatitis B infection
详细描述
This is a single center, open-label, study to evaluate the intra-hepatic effect of inarigivir dose per day and three times per week on immune response and viral markers in virally suppressed patients with chronic hepatitis B infection
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
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged ≥ 21 to ≤ 70 years
- •Chronic hepatitis B infection defined as HBsAg positive and on NUC therapy for at least one year.
- •Have at least one prior documented result of HBV DNA ≤ 20 IU/mL LLOQ from a local laboratory, 6 or more months prior to Screening
- •HBV DNA ≤ 20 IU/mL at Screening tested by the Central Laboratory
- •Have been on a commercially available HBV oral antiviral (OAV) treatment(s) (tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening.
- •Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma
- •Must be willing and able to comply with all study requirements including two liver biopsies
- •Negative urine or serum pregnancy test (for women of childbearing potential documented within the 24-hour period prior to the first dose of test drug. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion. All fertile males must also refrain from sperm donation while on Active drug and for 3 months after completion of Active drug.
- •Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
排除标准
- •Any liver biopsy evidence of metavir F3 or F4 disease on any prior biopsy
- •Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices
- •Evidence of advanced fibrosis at screening as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals
- •Laboratory parameters not within defined thresholds: ALT or AST ≥ 40 IU, white blood cells < 4500 cells/μL (SI unit < 4.5 × 109/L), hemoglobin (HgB) < 12 g/dL (SI unit < 120 g/L) for females, < 13 g/dL (SI unit < 130 g/L) for males, platelets < 150,000 per μL (SI unit < 150 × 109/L), albumin < 3.5 g/dL (SI unit < 35 g/L), international normalized ratio (INR) > 1.5, total bilirubin > 1.2 mg/dL (SI unit > 20.52 μmol/L), or alpha-fetoprotein (AFP) > 50 ng/mL (SI unit > 180.25 nmol/L). Patients with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. Patients with an AFP > 50 ng/mL but ˂ 500 ng/mL can be included if computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months shows no evidence of hepatocellular carcinoma.
- •Creatinine > 1.2 mg/dL (SI unit > 106.08 μmol/L), creatinine clearance < 50 mL/min (SI unit < 0.83 L/s/m2)
- •Co-infection with hepatitis C virus, human immunodeficiency virus, or hepatitis D virus
- •Evidence or history of hepatocellular carcinoma
- •Malignancy within 5 years prior to Screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Patients under evaluation for possible malignancy are not eligible.
- •Significant cardiovascular, pulmonary, or neurological disease
- •Received solid organ or bone marrow transplant
- •Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics (e.g., monoclonal antibody, Interferon)
- •Patients currently taking medication(s) that are transported through organic anion transporting polypeptide 1 including, but not limited to, atazanavir, rifampin, cyclosporine, eltrombopag, gemfibrozil, lopinavir/ritonavir, and saquinavir
- •Use of any herbal medications or supplements during the study period
- •Use of another investigational agent within 3 months of Screening
- •Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance
- •Females who are pregnant or may wish to become pregnant during the study
- •If the Investigator believes the prospective patient will not be able to comply with the requirements of the protocol and complete the study
- •Any medical condition, in the opinion of the Investigator, that could interfere with evaluation of the study objectives or safety of the patients
研究组 & 干预措施
Treatment A: inarigivir soproxil
Experimental
Inarigivir 400 mg once per day for 6 weeks (2800mg/week).
干预措施: inarigivir soproxil (Drug)
Treatment B: inarigivir soproxil
Experimental
Inarigivir 400 mg three times per week for 6 weeks (1200mg/week).
干预措施: inarigivir soproxil (Drug)
结局指标
主要结局
Change in intra-hepatic immune response
时间窗: 6 Weeks
Relative change from Baseline to Week 6 of intra-hepatic immune response (quantitative measurement of 500-600 genes using Nanostring technology) in hepatocytes and liver immune cells derived from the central immunology core biopsy
Change in intra-hepatic anti-viral response
时间窗: 6 Weeks
Relative change from Baseline to Week 6 of intra-hepatic anti-viral response (HBV DNA, HBV RNA, HBV core levels, cccDNA and HBsAg levels) using PCR assays in hepatocytes and liver immune cells derived from the intra-hepatic virology biopsy.
次要结局
- Characterization of hepatic immune cells(6 weeks)
- Proportion of patients with an adverse event (AE), or a clinically significant clinical laboratory abnormality(6 weeks)
- Correlation of change of intra-hepatic immune markers, serum cytokines and PBMC activation(6 weeks)
- Correlation of change of intra-hepatic antiviral response and serum anti-viral response(6 weeks)
- Comparison of change of intra-hepatic biomarkers of immune activation(6 weeks)
- Characterization of exhaustion markers(6 weeks)
- Comparison of change of peripheral biomarkers of immune activation(6 weeks)
- Comparison of change of anti-viral response(6 weeks)
研究者
研究点 (1)
Loading locations...
相似试验
终止
2 期
Evaluating the Safety and Efficacy of Inarigivir in Non-cirrhotic Treatment Naive Subjects Infected With Hepatitis B VirusHBVHepatitis B, ChronicHepatitis BNCT04059198F-star Therapeutics, Inc.5
终止
2 期
Evaluating the Safety and Efficacy of Inarigivir in Non-cirrhotic, Hepatitis B e Antigen-negative Subjects Infected With HBV Virus and Receiving or Stopping Treatment With a NUC InhibitorHBVHepatitis B, ChronicHepatitis BNCT04023721F-star Therapeutics, Inc.64
已完成
2 期
Doravirine/Islatravir (DOR/ISL) in Pediatric Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are <18 Years of Age and Weigh ≥35 kg (MK-8591A-028)HIV-1 InfectionNCT04295772Merck Sharp & Dohme LLC42
招募中
2 期
Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain MetastasesAdvanced GlioblastomaMetastatic Melanoma in the Central Nervous SystemMGMT-Unmethylated GlioblastomaNCT05909618Sheba Medical Center33
已完成
1 期
Surufatinib Hepatic Impairment StudyHepatic ImpairmentNCT04755075Hutchison Medipharma Limited16