A Study of Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) Combination Therapy in Participants With Chronic Hepatitis C (CHC) and Various Degrees of Renal Impairment

Phase 4

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: Peginterferon alfa-2a; Drug: Ribavirin

• Registration Number: NCT02864199
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This study will evaluate the pharmacokinetics (area under the curve \[AUC\], maximum concentration \[Cmax\], and other parameters) and tolerability of peginterferon alfa-2a and ribavirin combination therapy following single and multiple doses in participants with CHC infection and moderate to severe renal impairment or end-stage renal disease (ESRD) receiving hemodialysis. The anticipated time on study treatment is up to 48 weeks, and the target sample size is 48 individuals.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-02
• Primary Completion: 2007-09
• Study Completion: 2007-09
• Status Verified: 2016-08
• Study First Submitted: 2016-08-09
• Study First Submitted QC: 2016-08-09
• Last Update Submitted: 2016-08-09
• Study First Posted: 2016-08-11
• Last Update Posted: 2016-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

• Adults 18 to 65 years of age
• CHC infection as shown on enzyme-linked immunosorbent assay (ELISA) and radioimmunoblot assay (RIBA) or quantifiable hepatitis C virus (HCV) ribonucleic acid (RNA) greater than (>) 2000 copies per milliliter (copies/mL)
• Use of two forms of contraception during study and 6 months after the study in both men and women
• Normal renal function (creatinine clearance [CrCl] >80 milliliters per minute [mL/min]), moderate renal impairment (CrCl 30 to 50 mL/min), severe renal impairment (CrCl less than [<] 30 mL/min), or ESRD requiring hemodialysis
• Patients with ESRD must have been undergoing hemodialysis for at least 2 months

Exclusion Criteria

• Women who are pregnant or breastfeeding
• Male partners of women who are pregnant
• Conditions associated with decompensated and/or chronic liver disease
• Human immunodeficiency virus (HIV) infection
• Interferon or ribavirin treatment within the previous 3 months
• Poor hematologic function, including unstable hemoglobin
• Significant comorbidity or severe illness which would make the participant unsuitable for the study
• Acute renal failure

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group C: Hemodialysis/ESRD	Ribavirin	Participants requiring hemodialysis will receive 12 weeks of peginterferon alfa-2a, 135 mcg via SC injection once weekly, in combination with ribavirin, 200 mg PO every morning. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.
Group D: Normal Renal Function	Peginterferon alfa-2a	Participants with CrCl \>80 mL/min will receive 12 weeks of peginterferon alfa-2a, 180 mcg via SC injection once weekly, in combination with ribavirin, 800 to 1200 mg PO daily in two divided doses. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.
Group A: Moderate Renal Impairment	Peginterferon alfa-2a	Participants with CrCl 30 to 50 mL/min will receive 12 weeks of peginterferon alfa-2a, 180 micrograms (mcg) via subcutaneous (SC) injection once weekly, in combination with ribavirin, 600 milligrams (mg) orally (PO) daily in two divided doses. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.
Group B: Severe Renal Impairment	Ribavirin	Participants with CrCl \<30 mL/min will receive 12 weeks of peginterferon alfa-2a, 180 mcg via SC injection once weekly, in combination with ribavirin, 400 mg PO daily in two divided doses. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.
Group A: Moderate Renal Impairment	Ribavirin	Participants with CrCl 30 to 50 mL/min will receive 12 weeks of peginterferon alfa-2a, 180 micrograms (mcg) via subcutaneous (SC) injection once weekly, in combination with ribavirin, 600 milligrams (mg) orally (PO) daily in two divided doses. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.
Group B: Severe Renal Impairment	Peginterferon alfa-2a	Participants with CrCl \<30 mL/min will receive 12 weeks of peginterferon alfa-2a, 180 mcg via SC injection once weekly, in combination with ribavirin, 400 mg PO daily in two divided doses. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.
Group C: Hemodialysis/ESRD	Peginterferon alfa-2a	Participants requiring hemodialysis will receive 12 weeks of peginterferon alfa-2a, 135 mcg via SC injection once weekly, in combination with ribavirin, 200 mg PO every morning. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.
Group D: Normal Renal Function	Ribavirin	Participants with CrCl \>80 mL/min will receive 12 weeks of peginterferon alfa-2a, 180 mcg via SC injection once weekly, in combination with ribavirin, 800 to 1200 mg PO daily in two divided doses. Those with Genotype 2 or 3 disease may receive an additional 12 weeks of the same regimen, and those with another genotype may receive an additional 36 weeks.

Primary Outcome Measures

Name	Time	Method
Cmax of peginterferon alfa-2a	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
CL/F of ribavirin	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
Percentage of participants with undetectable HCV RNA level	Week 12
Cmax of ribavirin	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
AUC of ribavirin	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
AUC of peginterferon alfa-2a	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
Clearance (CL/F) of peginterferon alfa-2a	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12

Secondary Outcome Measures

Name	Time	Method
Time of maximum concentration (Tmax) of peginterferon alfa-2a	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
Tmax of ribavirin	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
Plasma concentration of ribavirin	Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12
Percentage of participants with adverse events (AEs)	From Baseline to Week 12 (or up to Week 48 if treatment continued)
Percentage of participants with a dose modification or premature withdrawal for safety reasons	From Baseline to Week 12 (or up to Week 48 if treatment continued)