Boceprevir in End Stage Renal Disease (ESRD)

End Stage Renal Disease Clinical Trial

Official title:

Prospective, Single-Center, Open Label, Pilot Study of Safety and Efficacy of Triple Anti-Viral Therapy With Pegylated Interferon, Ribavirin, and Boceprevir in Patients With Genotype 1 Chronic HCV With End Stage Renal Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02112630
• Other study ID #: AAAL5200
• Status: Withdrawn
• Phase: N/A
• First received: April 2, 2014
• Last updated: September 21, 2015
• Start date: May 2013
• Est. completion date: February 2015

Study information

• Verified date: September 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the safety and efficacy of triple therapy with pegylated interferon (P-IFN), ribavirin and boceprevir in patients with genotype 1 chronic Hepatitis C Virus (HCV) infection and end stage renal disease (ESRD) on hemodialysis (HD).

Description:

Hepatitis C (HCV) remains the most common chronic infection in the United States with about 3 million people chronically infected. The majority of these patients in the U.S. have genotype 1 HCV infection, which has been the most difficult genotype to treat with the traditional regimen of pegylated-interferon (P-IFN) and ribavirin, leading to sustained virologic response (SVR) in less than 50% of cases. HCV is also an established risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD) and unfortunately the treatment is even less successful in these patients mainly limited by increased medication toxicity.

In spring of 2011, the FDA approved two new direct acting antivirals (DAA) for the treatment of chronic genotype 1 HCV, boceprevir and telaprevir, to be used in combination with Peg-IFN and ribavirin. This 'triple therapy' approach has significantly increased the response rate (increased SVR rates to about 80% in those patients who had never been previously treated) representing a significant advance in the field. In addition, several response-guided therapy approaches were tested to determine if treatment duration could be shortened based upon the virologic response on treatment.

To date, there have been no studies evaluating the safety and efficacy of triple therapy in patients with ESRD. However, a single dose pharmacokinetic study of boceprevir in subjects with ESRD on hemodialysis demonstrated that the mean maximum concentration achieved by boceprevir (Cmax) and bioavailability (AUC) were comparable in patients with ESRD and in healthy subjects. Mean t½, median Tmax and mean apparent oral total clearance (CL/F) values were also similar in healthy subjects and patients with ESRD. Boceprevir exposure was also similar on dialysis and non-dialysis days. These data suggest that boceprevir does not need to be adjusted in patients with ESRD on dialysis, and that it is not removed by hemodialysis. To date, there are no studies of telaprevir in ESRD patients.

The investigators therefore aim to study the safety and efficacy of triple therapy using boceprevir in combination with P-IFN and ribavirin in patients with stage 5 CKD (defined as glomerular filtration rate (GFR) < 15 mL.min.1.73m2 on permanent hemodialysis for stage 5). In addition, given the significant toxicity of treatment in this particular patient population, the investigators aim to study the efficacy of response guided therapy in those patients who are eligible for response-guided therapy based on prior studies (treatment naïve patients, and well documented history of relapse with prior treatment with P-IFN and ribavirin).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Adult (ages 18-75)

2. Hepatitis C Virus ribonucleic acid (HCV RNA) 1000 IU/mL or greater

3. Hepatitis C Virus (HCV) genotype 1

4. End stage renal disease on hemodialysis

5. Females of child bearing potential must be using an adequate method of contraception throughout the study and must have a negative pregnancy test prior to the start of treatment.

Exclusion Criteria:

1. Intolerance to peg-IFN or ribavirin with prior treatment course.

2. Prior treatment with protease inhibitor (telaprevir or boceprevir) or experimental protease inhibitor

3. Significant cytopenias:

1. Absolute neutrophil count (ANC) < 1000/mm3, OR

2. Hemoglobin (Hgb) <10.5 g/dL, or

3. Platelet count < 50,000/mm3

4. Significant laboratory abnormalities

1. Direct bilirubin > 1.5 x upper limit of normal (ULN)

2. Total bilirubin > 1.6 mg/dL unless due to Gilbert's disease

3. Prothrombin time (PT)/Partial thromboplastin time (PTT) > 10% above laboratory reference range

4. Thyroid Stimulating Hormone (TSH) > 1.2 x ULN or < 0.8 x lower limit of normal (LLN)

5. Uncontrolled depression or psychiatric disease

6. Uncontrolled cardiopulmonary or cardiovascular disease

7. Autoimmune diseases except for treated thyroid disease

8. Active substance abuse within 6 months of initiation of treatment

9. Recent (within 4 weeks) episode of infection requiring systemic antibiotics

10. Any medical condition that would be predicted to be exacerbated by therapy or that would limit study participation

11. Any medical condition requiring or likely to require chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study

12. Human immunodeficiency virus (HIV) or Hepatitis B Virus (HBV) co-infection

13. Hepatocellular carcinoma (HCC) (Patients with HCC who are listed for liver transplantation may be included.)

14. Other significant chronic liver disease diagnosis

15. Evidence of decompensated liver disease

16. Solid organ transplant recipient (Patients who have a history of renal transplant, and have experienced kidney graft loss, and are not on immunosuppression may be included.)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End Stage Renal Disease
• Hepatitis C
• Hepatitis C Infection
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• P-IFN alfa 2a
P-IFN alfa 2b 0.75 mcg/kg/week
• P-IFN alfa 2b
P-IFN alfa 2a 135 mcg/kg/week
• Ribavirin
200 mg PO once daily or 200 mg PO three times a week
• Boceprevir
800 mg PO three times daily starting at week 4

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who achieve sustained virologic response	Primary efficacy is the proportion of patients who achieve sustained virologic response at week 12 after discontinuation of all therapy (SVR12).	Up to 12 weeks after discontinuation of all therapy	No