A Triple Combination Therapy Study of Boceprevir, Pegasys and Copegus in Previously Untreated Patients With Genotype 1 Chronic Hepatitis C

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01591460
First received: May 2, 2012
Last updated: August 7, 2015
Last verified: August 2015
  Purpose

This open-label, multicenter, treatment response guided study will evaluate the sustained virological response and safety of the triple combination therapy boceprevir, Pegasys (peginterferon alfa-2a) and Copegus (Ribavirin) in previously untreated patients with genotype 1 chronic hepatitis C. In the lead-in phase, patients will receive a dual combination therapy of Pegasys and Copegus for 4 weeks. In the following triple combination therapy phase, 800 mg boceprevir, 180 mcg Pegasys and 1000-1200 mg Copegus will be administered for 24, 32 or 44 weeks; the duration depending on the patient's treatment response. The anticipated time on study treatment is up to 48 weeks.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: boceprevir
Drug: peginterferon alfa-2a [Pegasys]
Drug: ribavirin (Copegus]
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An International, Multicenter, Open-Label Study Evaluating Sustained Virological Response and Safety With Boceprevir in Triple Combination Therapy With Peginterferon Alfa-2a (40KD) and Ribavirin in Treatment-Naïve Patients With Genotype 1 Chronic Hepatitis C

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virological Response (SVR) at 12 Weeks After End of Treatment (EOT) [ Time Frame: At 12 weeks after EOT (up to 60 weeks) ] [ Designated as safety issue: No ]
    SVR at 12 weeks after EOT was defined as an undetectable HCV RNA viral load obtained 12 weeks following completion of treatment. HCV RNA viral load was measured using the Roche COBAS TaqMan 2.0 HCV Test, with a lower limit of detection (LOD) of 10 to 15 international units per milliliter (IU/mL). The percentage of participants with SVR was calculated as [number of participants with undetectable HCV RNA at 12 weeks after EOT divided by the number of participants analyzed] multiplied by 100.


Secondary Outcome Measures:
  • Percentage of Participants With SVR at 24 Weeks After EOT [ Time Frame: At 24 weeks after EOT (up to 72 weeks) ] [ Designated as safety issue: No ]
    SVR at 24 weeks after EOT was defined as an undetectable HCV RNA viral load obtained 24 weeks following completion of treatment. HCV RNA viral load was measured using the Roche COBAS TaqMan 2.0 HCV Test, with a lower LOD of 10 to 15 IU/mL. The percentage of participants with SVR was calculated as [number of participants with undetectable HCV RNA at 24 weeks after EOT divided by the number of participants analyzed] multiplied by 100.

  • HCV RNA Levels [ Time Frame: At Baseline; Weeks 2, 4, 6, 8, 12, 16, 24, 28, and 36; EOT; and 12 and 24 weeks after EOT (up to 72 weeks) ] [ Designated as safety issue: No ]
    HCV RNA levels were obtained routinely during and after treatment. Mean HCV RNA levels were calculated by averaging the HCV RNA levels among all participants analyzed at each collection timepoint and expressed in log10 IU/mL.

  • Percentage of Participants With Virological Response [ Time Frame: At Weeks 2, 4, 6, 8, 12, 16, 24, 28, and 36; and EOT (up to 48 weeks) ] [ Designated as safety issue: No ]
    HCV RNA levels were obtained routinely during and after treatment. The percentage of participants with undetectable HCV RNA viral load (ie, virological response) was calculated as [number of participants with undetectable HCV RNA at each timepoint divided by the number of participants analyzed] multiplied by 100.

  • Percentage of Participants With at Least a 1-Log, 2-Log, or 3-Log Reduction in HCV RNA [ Time Frame: At Weeks 2, 4, 6, 8, 12, 16, 24, and 28 ] [ Designated as safety issue: No ]
    HCV RNA levels were obtained routinely during and after treatment. Reductions in HCV RNA viral load by 1-log, 2-log, or 3-log increments were determined relative to Baseline HCV RNA. Each increment represents a reduction greater than or equal to (≥) the specified log value, including results for which HCV RNA was below the limit of quantification (25 IU/mL). The percentage of participants with each log reduction in HCV RNA was calculated as [number of participants with log reduction divided by the number of participants analyzed] multiplied by 100.

  • Percentage of Participants With Virological Relapse Following EOT Response [ Time Frame: Up to 72 weeks (at 12 and 24 weeks after EOT) ] [ Designated as safety issue: No ]
    Virological relapse was defined as a detectable post-treatment HCV RNA viral load following a previously undetectable EOT level (ie, virological response). The percentage of participants with virological relapse was calculated as [number of participants meeting the above criteria divided by the number of participants analyzed] multiplied by 100.

  • Percentage of Participants With Virological Breakthrough Following On-Treatment Response [ Time Frame: Up to 48 weeks (at Baseline; Weeks 2, 4, 6, 8, 12, 16, 24, 28, and 36; and EOT) ] [ Designated as safety issue: No ]
    Virological breakthrough was defined as an HCV RNA viral load greater than (>) 1000 IU/mL following a previously undetectable level at any time during treatment (ie, virological response). Participants who ultimately achieved an EOT response were not considered for virological breakthrough. The percentage of participants with virological breakthrough was calculated as [number of participants meeting the above criteria divided by the number of participants analyzed] multiplied by 100.

  • Percentage of Participants With Virological Rebound Following On-Treatment Decline in HCV RNA [ Time Frame: Up to 48 weeks (at Baseline; Weeks 2, 4, 6, 8, 12, 16, 24, 28, and 36; and EOT) ] [ Designated as safety issue: No ]
    Virological rebound was defined as an HCV RNA viral load >1000 IU/mL and a ≥1-log increase from nadir following a decline in HCV RNA from Baseline at any time during treatment (ie, on-treatment decline). Participants who ultimately achieved an EOT response were not considered for virological rebound. The percentage of participants with virological rebound was calculated as [number of participants meeting the above criteria divided by the number of participants analyzed] multiplied by 100.

  • Percentage of Participants With Treatment Discontinued Based Upon Elevated (Week 12) or Detectable (Week 24) HCV RNA [ Time Frame: At 12 and 24 weeks ] [ Designated as safety issue: No ]
    Treatment was to be discontinued for participants who met prespecified criteria, termed the futility rule, after 12 or 24 weeks of treatment. Participants were discontinued from treatment for one of the following reasons: HCV RNA viral load ≥100 IU/mL (Week 12) or a detectable HCV RNA viral load (Week 24). HCV RNA viral load was measured using the Roche COBAS TaqMan 2.0 HCV Test, with a lower LOD of 10 to 15 IU/mL. The percentage of participants with treatment discontinued for each reason was calculated as [number of participants meeting one of the above criteria divided by the number of participants analyzed] multiplied by 100.

  • Duration of Treatment With PEG-IFN, RBV, and Boceprevir [ Time Frame: Up to 48 weeks (from Baseline until EOT) ] [ Designated as safety issue: No ]
    The duration of treatment with each study drug was determined as the time from treatment start until the last dose of PEG-IFN, RBV, or boceprevir. Median duration of treatment was determined using the actual duration of treatment among individual participants and expressed in weeks.

  • Percentage of Participants With a Dose Modification of PEG-IFN, RBV, or Boceprevir By Reason [ Time Frame: Up to 48 weeks (from Baseline until EOT) ] [ Designated as safety issue: No ]
    Dose modifications for each study drug included any dose reduction, treatment interruption, or premature withdrawal. Adverse event (AE)-related reasons were documented, as well as reasons related to insufficient efficacy ('Poor efficacy') or other safety-related reasons ('Safety/other'). The percentage of participants with a dose modification documented for each reason was calculated as [number of participants with dose modification divided by the number of participants analyzed] multiplied by 100.

  • Percentage of Participants Receiving Target Administrations of PEG-IFN, RBV, and Boceprevir [ Time Frame: Up to 48 weeks (from Baseline until EOT) ] [ Designated as safety issue: No ]
    The frequency of missed treatments was examined using the number of administrations received as a percentage of target administrations for each study drug. The maximum number of possible administrations was considered in terms of once-weekly injections with PEG-IFN and in terms of treatment days with RBV and boceprevir. The percentage of target administrations each participant received was separated into ranges of <60%, 60 to <80%, 80 to <95%, and ≥95% for each study drug. The percentage of participants who received each range of target administrations was calculated as [number of participants in each range divided by the number of participants analyzed] multiplied by 100.

  • Number of Participants With a Safety-Related Dose Modification [ Time Frame: Up to 48 weeks (from Baseline until EOT) ] [ Designated as safety issue: No ]
    Dose modifications for each study drug included any dose reduction, treatment interruption, or premature withdrawal. The percentage of participants with a safety-related dose modification (eg, modification due to adverse event or laboratory abnormality) of any study drug was calculated as [number of participants with dose modification divided by the number of participants analyzed] multiplied by 100.

  • Time to Safety-Related Dose Modification [ Time Frame: Up to 48 weeks (from Baseline until EOT) ] [ Designated as safety issue: No ]
    Dose modifications for each study drug included any dose reduction, treatment interruption, or premature withdrawal. Median time to safety-related dose modification (eg, modification due to adverse event or laboratory abnormality) of any study drug was estimated using Kaplan-Meier and expressed in weeks.

  • Percentage of Participants Using Concomitant Hematopoietic Stimulants During Treatment and Follow-Up [ Time Frame: Up to 72 weeks (from Baseline until 24 weeks after EOT) ] [ Designated as safety issue: No ]
    Use of concomitant hematopoietic stimulants (such as epoetin) during the 48-week treatment period and/or within 24 weeks of follow-up was documented. The percentage of participants using concomitant hematopoietic stimulants was calculated as [number of participants reporting concomitant use divided by the number of participants analyzed] multiplied by 100.

  • Percentage of Participants With a Concomitant Disease Prior to or During the Study [ Time Frame: Up to 76 weeks (from Screening until 24 weeks after EOT) ] [ Designated as safety issue: No ]
    The prevalence of concomitant disease at any time from Screening through the end of follow-up was documented. The percentage of participants with a concomitant disease was calculated as [number of participants reporting or diagnosed with concomitant disease divided by the number of participants analyzed] multiplied by 100. Diseases documented for ≥5% of participants included hypertension, diabetes mellitus, hypothyroidism, and vitamin D deficiency as reported here.

  • Percentage of Participants Using Concomitant Medications During Treatment and Follow-Up [ Time Frame: Up to 72 weeks (from Baseline until 24 weeks after EOT) ] [ Designated as safety issue: No ]
    Use of concomitant prescription or nonprescription medications during the 48-week treatment period and/or within 24 weeks of follow-up was documented. The percentage of participants using concomitant medications was calculated as [number of participants reporting concomitant use divided by the number of participants analyzed] multiplied by 100. Medication classes reported by >10% of participants included analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, corticosteroids, proton pump inhibitors, vitamins and minerals, and beta-adrenoceptor blocking agents as reported here.


Enrollment: 165
Study Start Date: August 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dual Combination Therapy Drug: peginterferon alfa-2a [Pegasys]
180 mcg subcutaneously once a week for 4 weeks
Drug: ribavirin (Copegus]
1000 mg or 1200 mg orally once a day for 4 weeks
Experimental: Triple Combination Therapy Drug: boceprevir
800 mg three times daily for 24, 32 or 44 weeks
Drug: peginterferon alfa-2a [Pegasys]
180 mcg subcutaneously once a week for 24, 32 or 44 weeks
Drug: ribavirin (Copegus]
1000 mg or 1200 mg orally once a day for 24, 32 or 44 weeks

  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
  • Chronic liver disease consistent with chronic hepatitis C, genotype 1 infection
  • Serum HCV RNA quantifiable at screening
  • Patients who have not been previously treated with pegylated interferon (IFN), standard IFN, RBV or any direct acting anti-viral agent
  • Compensated liver disease (Child-Pugh Grade A clinical classification for patients with cirrhosis: total score </=6)
  • Negative urine or blood pregnancy test (for women of childbearing potential)

Exclusion Criteria:

  • Women with ongoing pregnancy or breast feeding
  • Male partners of women who are pregnant
  • Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment </=6 months prior to the first dose of study drug
  • Any investigational drug </=6 weeks prior to the first dose of study drug
  • History or other evidence of decompensated liver disease
  • History or other evidence of a medical condition associated with chronic liver disease other than chronic hepatitis C
  • Signs or symptoms of hepatocellular carcinoma
  • Co-infection with HCV genotypes other than genotype 1
  • Co-infection with hepatitis A, hepatitis B, and/or human immunodeficiency virus (HIV)
  • Any patient with an increased risk for anemia
  • History of severe psychiatric disease
  • History of immunologically mediated, chronic pulmonary, or severe cardiac disease
  • Current diseases that are not adequately controlled
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01591460

Locations
Austria
Graz, Austria, 8036
Innsbruck, Austria, 6020
Linz, Austria, 4010
Wien, Austria, 1100
Wien, Austria, 1160
Wien, Austria, 1090
Germany
Dortmund, Germany, 44263
Frankfurt am Main, Germany, 60594
Hamburg, Germany, 20099
Hannover, Germany, 30625
Oberhausen, Germany, 46145
Hungary
Budapest, Hungary, 1088
Budapest, Hungary, 1097
Budapest, Hungary, 1126
Debrecen, Hungary, 4032
Kaposvar, Hungary, 7400
Pecs, Hungary, 7624
Poland
Bialystok, Poland, 15-540
Bydgoszcz, Poland, 85-030
Chorzow, Poland, 41-500
Lublin, Poland, 20-081
Wrocław, Poland, 50-349
Łodz, Poland, 91-347
Romania
Bucharest, Romania, 030303
Bucharest, Romania, 022328
Bucharest, Romania, 021105
Constanta, Romania, 900635
Timisoara, Romania, 300167
Spain
Vigo, Pontevedra, Spain, 36200
Baracaldo, Vizcaya, Spain, 48903
Granada, Spain, 18012
Zaragoza, Spain, 50009
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: NCT01591460     History of Changes
Other Study ID Numbers: MV28073, 2011-004810-41
Study First Received: May 2, 2012
Results First Received: July 10, 2015
Last Updated: August 7, 2015
Health Authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen - AGES Pharm Med

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on August 31, 2015