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A Study of RO5024048 in Combination With Ritonavir-Boosted Danoprevir and Pegasys/Copegus in Patients With Chronic Hepatitis C Genotype 1 Who Have Failed Prior HCV Protease Inhibitor Treatment

Primary Purpose

Hepatitis C, Chronic

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

RO5024048

danoprevir

peginterferon alfa-2a [Pegasys]

ribavirin [Copegus]

ritonavir

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult patients, >/= 18 years of age
Hepatitis C genotype 1 infection
Serum HCV quantifiable by Roche COBAS TaqMan HCV Test v2.0
Liver biopsy (within 24 months) or Fibroscan (within 12 months) before first administration of study drug consistent with chronic hepatitis C and demonstrating absence of liver cirrhosis
Documented failed prior treatment with protease inhibitor (evidenced by viral breakthrough or partial response while on treatment or relapse after treatment), including documentation on treatment with other direct-acting antiviral agents and other HCV antiviral treatment
Patients must have discontinued prior HCV treatment at least 24 weeks prior to first dose of study drug in this trial

Exclusion Criteria:

Infection with any HCV genotype other than genotype 1
Evidence of any variants associated with protease inhibitor resistance at screening
Body mass index (BMI) <18 or >/=36 kg/m2
Positive for hepatitis A or hepatitis B infection
Use of any systemic antiviral therapy with perceived activity against HCV </=1 month prior to first dose of study drug
History or evidence of a medical condition associated with chronic liver disease other than chronic hepatitis C
Pregnant or breastfeeding women
Males with female partners who are pregnant
History of immunologically mediated disease; patients with rheumatoid arthritis requiring only intermittent non-steroidal anti-inflammatory medications or with celiac disease will be allowed
History or evidence of decompensated liver disease
History or evidence of renal disease; patients with history of nephrolithiasis will be allowed
Uncontrolled Type 1 or 2 diabetes
History or evidence of chronic pulmonary disease associated with functional limitation
History of severe cardiac disease History of any neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin (e.g. basal or squamous cell carcinoma)
Evidence of excessive alcohol, drug or substance abuse (excluding marijuana use) within 1 year of the first dose of study drug

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

1000 mg 24 weeks

1000 mg 26 weeks

1500 mg 24 weeks

1500 mg 26 weeks

Arm Description

Outcomes

Primary Outcome Measures

Sustained virologic response (defined as unquantifiable serum HCV RNA) 12 weeks after treatment (SVR-12)

Secondary Outcome Measures

Sustained virologic response 4 weeks after treatment (SVR-4)

Sustained virologic response 24 weeks after treatment (SVR-24)

Change in serum HCV RNA levels

Virologic response over time

Correlation between trough concentrations of RO4995855 and virologic response

Incidence of direct-acting antiviral (DAA) resistance, including re-emergence of protease inhibitor resistant virus

Safety: Incidence of adverse events

Full Information

NCT ID

NCT01579019

First Posted

April 16, 2012

Last Updated

November 1, 2016

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01579019

Brief Title

A Study of RO5024048 in Combination With Ritonavir-Boosted Danoprevir and Pegasys/Copegus in Patients With Chronic Hepatitis C Genotype 1 Who Have Failed Prior HCV Protease Inhibitor Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Withdrawn

Study Start Date

July 2012 (undefined)

Primary Completion Date

March 2014 (Anticipated)

Study Completion Date

March 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

This randomized, double blind, phase II study will evaluate the efficacy and safety of two doses of RO5024048 in combination with ritonavir-boosted danoprevir and Pegasys (peginterferon alpha-2a) and Copegus (ribavirin) in patients who failed a prior protease inhibitor containing regimen with or without pegylated interferon. Patients will be randomized to receive either a 2-week lead-in of RO5024048 (1500 mg or 1000 mg orally twice daily) in combination with Pegasys (180 mcg subcutaneously weekly) and Copegus (1000 mg or 1200 mg orally daily) followed by 24 weeks of therapy with RO5024048 in combination with danoprevir (100 mg orally twice daily) plus ritonavir (100 mg orally twice daily) and Pegasys and Copegus (QUAD therapy), or 24 weeks of therapy with RO5024048 in combination with danoprevir plus ritonavir and Pegasys and Copegus (QUAD therapy). Anticipated time on study treatment is 24 or 26 weeks, with a treatment-free follow-up of 24 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1000 mg 24 weeks

Arm Type

Active Comparator

Arm Title

1000 mg 26 weeks

Arm Type

Active Comparator

Arm Title

1500 mg 24 weeks

Arm Type

Experimental

Arm Title

1500 mg 26 weeks

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

RO5024048

Intervention Description

1500 mg po bid, 24 or 26 weeks

Intervention Type

Drug

Intervention Name(s)

RO5024048

Intervention Description

1000 mg po bid, 24 or 26 weeks

Intervention Type

Drug

Intervention Name(s)

danoprevir

Intervention Description

100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26

Intervention Type

Drug

Intervention Name(s)

peginterferon alfa-2a [Pegasys]

Intervention Description

180 mcg sc qw, 24 or 26 weeks

Intervention Type

Drug

Intervention Name(s)

ribavirin [Copegus]

Intervention Description

1000 mg or 1200 mg po daily, 24 or 26 weeks

Intervention Type

Drug

Intervention Name(s)

ritonavir

Intervention Description

100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26

Primary Outcome Measure Information:

Title

Sustained virologic response (defined as unquantifiable serum HCV RNA) 12 weeks after treatment (SVR-12)

Time Frame

approximately 2 years

Secondary Outcome Measure Information:

Title

Sustained virologic response 4 weeks after treatment (SVR-4)

Time Frame

approximately 2 years

Title

Sustained virologic response 24 weeks after treatment (SVR-24)

Time Frame

approximately 2 years

Title

Change in serum HCV RNA levels

Time Frame

from baseline to Week 12

Title

Virologic response over time

Time Frame

from baseline to 24 weeks after treatment

Title

Correlation between trough concentrations of RO4995855 and virologic response

Time Frame

approximately 2 years

Title

Incidence of direct-acting antiviral (DAA) resistance, including re-emergence of protease inhibitor resistant virus

Time Frame

approximately 2 years

Title

Safety: Incidence of adverse events

Time Frame

approximately 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients, >/= 18 years of age Hepatitis C genotype 1 infection Serum HCV quantifiable by Roche COBAS TaqMan HCV Test v2.0 Liver biopsy (within 24 months) or Fibroscan (within 12 months) before first administration of study drug consistent with chronic hepatitis C and demonstrating absence of liver cirrhosis Documented failed prior treatment with protease inhibitor (evidenced by viral breakthrough or partial response while on treatment or relapse after treatment), including documentation on treatment with other direct-acting antiviral agents and other HCV antiviral treatment Patients must have discontinued prior HCV treatment at least 24 weeks prior to first dose of study drug in this trial Exclusion Criteria: Infection with any HCV genotype other than genotype 1 Evidence of any variants associated with protease inhibitor resistance at screening Body mass index (BMI) <18 or >/=36 kg/m2 Positive for hepatitis A or hepatitis B infection Use of any systemic antiviral therapy with perceived activity against HCV </=1 month prior to first dose of study drug History or evidence of a medical condition associated with chronic liver disease other than chronic hepatitis C Pregnant or breastfeeding women Males with female partners who are pregnant History of immunologically mediated disease; patients with rheumatoid arthritis requiring only intermittent non-steroidal anti-inflammatory medications or with celiac disease will be allowed History or evidence of decompensated liver disease History or evidence of renal disease; patients with history of nephrolithiasis will be allowed Uncontrolled Type 1 or 2 diabetes History or evidence of chronic pulmonary disease associated with functional limitation History of severe cardiac disease History of any neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin (e.g. basal or squamous cell carcinoma) Evidence of excessive alcohol, drug or substance abuse (excluding marijuana use) within 1 year of the first dose of study drug

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

12. IPD Sharing Statement

Learn more about this trial

A Study of RO5024048 in Combination With Ritonavir-Boosted Danoprevir and Pegasys/Copegus in Patients With Chronic Hepatitis C Genotype 1 Who Have Failed Prior HCV Protease Inhibitor Treatment

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