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

Primary Purpose

Hepatitis C, Chronic

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

boceprevir

peginterferon alfa-2a [Pegasys]

ribavirin (Copegus]

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
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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dual Combination Therapy

Triple Combination Therapy

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Virological Response (SVR) at 12 Weeks After End of Treatment (EOT)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Full Information

NCT ID

NCT01591460

First Posted

May 2, 2012

Last Updated

November 1, 2016

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01591460

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

August 2012 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

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.

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 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

165 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dual Combination Therapy

Arm Type

Experimental

Arm Title

Triple Combination Therapy

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

boceprevir

Intervention Description

800 mg three times daily for 24, 32 or 44 weeks

Intervention Type

Drug

Intervention Name(s)

peginterferon alfa-2a [Pegasys]

Intervention Description

180 mcg subcutaneously once a week for 24, 32 or 44 weeks

Intervention Type

Drug

Intervention Name(s)

peginterferon alfa-2a [Pegasys]

Intervention Description

180 mcg subcutaneously once a week for 4 weeks

Intervention Type

Drug

Intervention Name(s)

ribavirin (Copegus]

Intervention Description

1000 mg or 1200 mg orally once a day for 24, 32 or 44 weeks

Intervention Type

Drug

Intervention Name(s)

ribavirin (Copegus]

Intervention Description

1000 mg or 1200 mg orally once a day for 4 weeks

Primary Outcome Measure Information:

Title

Percentage of Participants With Sustained Virological Response (SVR) at 12 Weeks After End of Treatment (EOT)

Description

Time Frame

At 12 weeks after EOT (up to 60 weeks)

Secondary Outcome Measure Information:

Title

Percentage of Participants With SVR at 24 Weeks After EOT

Description

Time Frame

At 24 weeks after EOT (up to 72 weeks)

Title

HCV RNA Levels

Description

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)

Title

Percentage of Participants With Virological Response

Description

Time Frame

At Weeks 2, 4, 6, 8, 12, 16, 24, 28, and 36; and EOT (up to 48 weeks)

Title

Percentage of Participants With at Least a 1-Log, 2-Log, or 3-Log Reduction in HCV RNA

Description

Time Frame

At Weeks 2, 4, 6, 8, 12, 16, 24, and 28

Title

Percentage of Participants With Virological Relapse Following EOT Response

Description

Time Frame

Up to 72 weeks (at 12 and 24 weeks after EOT)

Title

Percentage of Participants With Virological Breakthrough Following On-Treatment Response

Description

Time Frame

Up to 48 weeks (at Baseline; Weeks 2, 4, 6, 8, 12, 16, 24, 28, and 36; and EOT)

Title

Percentage of Participants With Virological Rebound Following On-Treatment Decline in HCV RNA

Description

Time Frame

Up to 48 weeks (at Baseline; Weeks 2, 4, 6, 8, 12, 16, 24, 28, and 36; and EOT)

Title

Percentage of Participants With Treatment Discontinued Based Upon Elevated (Week 12) or Detectable (Week 24) HCV RNA

Description

Time Frame

At 12 and 24 weeks

Title

Duration of Treatment With PEG-IFN, RBV, and Boceprevir

Description

Time Frame