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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hepatitis C, Chronic	Drug: RO5024048 Drug: peginterferon alfa-2a [Pegasys] Drug: ribavirin [Copegus] Drug: danoprevir Drug: ritonavir	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Ritonavir Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Sustained virologic response (defined as unquantifiable serum HCV RNA) 12 weeks after treatment (SVR-12) [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Sustained virologic response 4 weeks after treatment (SVR-4) [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Sustained virologic response 24 weeks after treatment (SVR-24) [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Change in serum HCV RNA levels [ Time Frame: from baseline to Week 12 ] [ Designated as safety issue: No ]
Virologic response over time [ Time Frame: from baseline to 24 weeks after treatment ] [ Designated as safety issue: No ]
Correlation between trough concentrations of RO4995855 and virologic response [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Incidence of direct-acting antiviral (DAA) resistance, including re-emergence of protease inhibitor resistant virus [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Safety: Incidence of adverse events [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]

Enrollment:	0
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1500 mg 26 weeks	Drug: RO5024048 1500 mg po bid, 24 or 26 weeks Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26 Drug: ritonavir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26
Active Comparator: 1000 mg 26 weeks	Drug: RO5024048 1000 mg po bid, 24 or 26 weeks Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26 Drug: ritonavir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26
Experimental: 1500 mg 24 weeks	Drug: RO5024048 1500 mg po bid, 24 or 26 weeks Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26 Drug: ritonavir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26
Active Comparator: 1000 mg 24 weeks	Drug: RO5024048 1000 mg po bid, 24 or 26 weeks Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01579019

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01579019 History of Changes
Other Study ID Numbers:	NV22877, 2010-022659-41
Study First Received:	April 16, 2012
Last Updated:	October 10, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Protease Inhibitors
Ritonavir

Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antimetabolites
HIV Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013