Host Mechanisms Involved in Achieving SVR Using Grazoprevir and Elbasvir in Treatment of Chronic Hepatitis C in Patients With CKD Before and After Renal Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- SVR 12
研究概览
简要总结
The purpose of this study is to determine whether patients treated for chronic hepatitis C (HCV) with zepatier (grazoprevir/elbasvir) prior to kidney transplant will have a stronger immune response compared to patients treated after kidney transplant. 25 patients with chronic kidney disease (CKD) and HCV will be treated with zepatier and 25 kidney transplant recipients with chronic kidney disease will be treated with zepatier. Blood markers of immune function will be monitored in both groups to determine their response to therapy.
详细描述
The study will be a pilot, prospective, single-center, open-label, non-randomized, non-controlled, parallel clinical trial. 25 HCV genotype 1 infected patients post transplant will be enrolled in the study. Recruitment will be conducted through the renal transplant and nephrology outpatient clinics at the University of Maryland.
The post-transplant cohort will include renal transplant recipients of both living donor and deceased donor organs infected with HCV prior to their transplantation with GFRs <50 with active HCV viremia. These patients will be recruited from the University of Maryland's multidisciplinary transplant nephrology clinic or infectious disease clinic.
Screening All patients will be screened at the Institute of Human Virology (IHV) Clinical Research Unit. At this visit, all patients will have screening labs drawn and a history and physical examination performed. Additional requirements will be genotype testing prior to enrollment, but after transplant and disease staging within 12 months of enrollment by liver biopsy, elastography, or biochemical testing. For those who do not have a genotype or disease staging within the specified time frame, genotyping and elastography will be repeated as part of the study screening work up. Eligibility will be determined based upon these results within 6 weeks of starting the study drugs.
Given the reduced efficacy of this regimen in patients with genotype 1a with the presence of baseline NS5A resistance-associated variants (RAVs), the investigators will screen patients for RAVs in patients with HCV genotype 1a at the time of enrollment. Any patient with genotype 1a HCV found to have NS5A RAVs will undergo 16 weeks of therapy according to current treatment guidelines.
Starting therapy Study drugs will be administered starting on day 0 after a history and physical examination is performed and safety labs are checked. All patients will sign an informed consent as approved by our Institutional Review Board (IRB) prior to administration of study drugs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •At least 18 years of age at the time of screening
- •Have stable renal function for one month (30 days) prior to enrollment
- •Have Chronic HCV infection prior to transplantation with documented HCV viremia ≥ 1,000 IU/ml at screening and either documented HCV Ab positivity or HCV viremia ≥ 1,000 IU/ml at least 6 months prior to enrollment.
- •Documented genotype 1 HCV infection prior to enrollment and after their transplant in the post-transplantation cohort
- •HCV disease staging within 12 months prior to enrollment by liver biopsy, transient elastography, or biochemical testing
- •Be able to give informed consent and comply with study guidelines
- •Women of childbearing age will be required to have a negative pregnancy test at enrollment and use birth control throughout the duration of treatment.
- •Inclusion Criteria Specific to the Pre-transplant Arm
- •Patients will either be:
- •On the transplant waiting list followed by the University of Maryland's nephrology clinic or the Baltimore VA's nephrology clinic
- •On chronic hemodialysis not yet on the transplant list and followed in the University's hemodialysis center or in the University's nephrology clinic
- •Have chronic kidney disease with GFR <50
- •Inclusion Criteria Specific to the Post-transplant Arm
- •Patients will have undergone renal transplantation no greater than five years prior to enrollment and will be followed in our University's nephrology and infectious disease clinic. They will all have stable renal function at the time of enrollment.
排除标准
- •Documented positive hepatitis B (HBV) surface antigen, and/or HBV DNA prior to enrollment
- •Any prior exposure to HCV protease inhibitor therapy
- •HIV co-infection if on a protease inhibitor based regimen
- •Increase in creatinine of 15% or greater within one month (30 days) of the screening visit
- •Evidence of hepatocellular carcinoma at the time of enrollment
- •Liver disease caused by an etiology other than HCV
- •F4 or decompensated cirrhotic patients
- •Child Pugh class B or C
- •AST or ALT >350 within 6 months prior to enrollment
- •Albumin < 3g/dL at the time of enrollment
- •Platelet count < 75 at the time of enrollment
- •History of clinically significant allergy or adverse event with protease inhibitors
- •Evidence of the acquisition of HCV at the time of or after transplantation
- •Pregnant or breastfeeding women
- •Cyclosporine; St. John's Wort; Efavirenz; Phenytoin; Carbamazepine; Bosentan; HIV protease inhibitors; modafinil; ketoconazole; or rifampin use within 7 days of enrollment
- •Coadministration of more than 20 mg atorvastatin; 10 mg rosuvastatin; 20 mg of fluvastatin, lovastatin or simvastatin
研究组 & 干预措施
Post-transplant
This arm will evaluate the treatment of patients with HCV and chronic kidney disease (GFR <50) who have had a kidney transplant using grazoprevir and elbasvir.
干预措施: Post-transplant Grazoprevir and Elbasvir (Drug)
结局指标
主要结局
SVR 12
时间窗: This will be measured at post-treatment week 12 (study week 24 or week 28 for those with resistance mutations)
Sustained virologic response (SVR) will be assessed by measuring the quantitative HCV viral load 12 weeks after completing treatment. This will be a measure of circulating HCV virus in participants off therapy, 12 weeks after finishing treatment, to determine the durability of the response to the treatment.
次要结局
- Change in T Cell Response(This will be collected at day 0, week 4, and week 12)
- Change in T Cell Immunophenotypes(This will be collected at day 0, week 4, and week 12)
- Quantification of Antiviral Cytokines(This will be collected at day 0 and week 4)
- Safety as Assessed by Adverse Event Monitoring, Including Routine Lab Work(This will be measured at day 0, weeks 2, 4, 8, 12 (and 16 if resistance mutations are present))
- Kidney Function(This will be measured at day 0, treatment week 2, treatment week 4, treatment week 8, treatment week 12, ( treatment week 16, if applicable), post-treatment week 4 (week 16/20), and post-treatment week 12 (week 24/28))
- Kidney Allograft Rejection(This will be measured at post-treatment week 12)
研究者
Jennifer Husson
Assistant Professor
University of Maryland, Baltimore