NCT01579019

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.

Trial Health

15
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2012

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 16, 2012

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 17, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

1.7 years

First QC Date

April 16, 2012

Last Update Submit

November 1, 2016

Conditions

Outcome Measures

Primary Outcomes (1)

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

    approximately 2 years

Secondary Outcomes (7)

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

    approximately 2 years

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

    approximately 2 years

  • Change in serum HCV RNA levels

    from baseline to Week 12

  • Virologic response over time

    from baseline to 24 weeks after treatment

  • Correlation between trough concentrations of RO4995855 and virologic response

    approximately 2 years

  • +2 more secondary outcomes

Study Arms (4)

1000 mg 24 weeks

ACTIVE COMPARATOR
Drug: RO5024048Drug: danoprevirDrug: peginterferon alfa-2a [Pegasys]Drug: ribavirin [Copegus]

1000 mg 26 weeks

ACTIVE COMPARATOR
Drug: RO5024048Drug: danoprevirDrug: peginterferon alfa-2a [Pegasys]Drug: ribavirin [Copegus]Drug: ritonavir

1500 mg 24 weeks

EXPERIMENTAL
Drug: RO5024048Drug: danoprevirDrug: peginterferon alfa-2a [Pegasys]Drug: ribavirin [Copegus]Drug: ritonavir

1500 mg 26 weeks

EXPERIMENTAL
Drug: RO5024048Drug: danoprevirDrug: peginterferon alfa-2a [Pegasys]Drug: ribavirin [Copegus]Drug: ritonavir

Interventions

1500 mg po bid, 24 or 26 weeks

1500 mg 24 weeks1500 mg 26 weeks

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

1000 mg 24 weeks1000 mg 26 weeks1500 mg 24 weeks1500 mg 26 weeks

180 mcg sc qw, 24 or 26 weeks

1000 mg 24 weeks1000 mg 26 weeks1500 mg 24 weeks1500 mg 26 weeks

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

1000 mg 24 weeks1000 mg 26 weeks1500 mg 24 weeks1500 mg 26 weeks

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

1000 mg 26 weeks1500 mg 24 weeks1500 mg 26 weeks

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

danoprevirpeginterferon alfa-2aRibavirinRitonavir

Condition Hierarchy (Ancestors)

Hepatitis CBlood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR
0

Study Design

Study Type
interventional
Phase
phase 2
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 16, 2012

First Posted

April 17, 2012

Study Start

July 1, 2012

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

November 2, 2016

Record last verified: 2016-11