Trial Outcomes & Findings for Efficacy of PegIntron (Peginterferon Alfa-2b) and Rebetol (Ribavirin) in Treatment-naïve Subjects With Chronic Hepatitis C in Clinical Practice in Greece (Study P05209) (NCT NCT00724464)

NCT ID: NCT00724464

Last Updated: 2015-10-19

Results Overview

Sustained virological response (SVR) was assessed at the 24-week post-treatment follow-up (Visit 2). SVR was defined as undetectable plasma Hepatitis C virus Ribonucleic acid (HCV-RNA) at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Recruitment status

COMPLETED

Target enrollment

332 participants

Primary outcome timeframe

24 weeks following completion of 24 or 48 weeks of therapy

Results posted on

2015-10-19

Participant Flow

401 participants were screened for eligibility. 332 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Pegylated Interferon Alpha-2b and Ribavirin Participants with CHC of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on HCV genotype and viral load followed by a 24-week post-treatment follow-up.
Overall Study STARTED	332
Overall Study COMPLETED	309
Overall Study NOT COMPLETED	23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of PegIntron (Peginterferon Alfa-2b) and Rebetol (Ribavirin) in Treatment-naïve Subjects With Chronic Hepatitis C in Clinical Practice in Greece (Study P05209)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=332 Participants Participants with CHC of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on HCV genotype and viral load followed by a 24-week post-treatment follow-up.
Age, Continuous	39.9 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	102 Participants n=5 Participants
Sex: Female, Male Male	230 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (EAS) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up.

Sustained virological response (SVR) was assessed at the 24-week post-treatment follow-up (Visit 2). SVR was defined as undetectable plasma Hepatitis C virus Ribonucleic acid (HCV-RNA) at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=309 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up	286 Participants

PRIMARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (EAS) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up.

Virological relapse was assessed at the 24-week post-treatment follow-up (Visit 2). Virological relapse was defined as undetectable plasma HCV-RNA at end of combination treatment (Visit 1- considered Week 24 or Week 48 after treatment start depending on treatment duration), but with positive HCV-RNA at the 24-week post treatment follow-up.

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=309 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Demonstrated Virological Relapse as Assessed at 24-week Post-treatment Follow-up	23 Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. 23 participants were relapsers.

SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV genotype (1, 2, 3, 4, or 2 \& 3) at baseline. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=286 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline Genotype 3	146 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline Genotype 4	30 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline Genotype 1	81 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline Genotype 2	28 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline Genotype 2 & 3	1 Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 157 participants.

SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on liver fibrosis stage, where biopsy was available, at baseline: absence, minimal, moderate, or significant as assessed by investigator. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=286 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline Absence	83 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline Minimal	27 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline Moderate	15 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline Significant	4 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline Missing	157 Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 32 participants.

SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV-RNA viral load at baseline as assessed by investigator. Low viral load was defined as \<400,000 International Units/milliliter (IU/mL) and high viral load was defined as \>=400,000 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=286 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline Low Viral Load	99 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline High Viral Load	155 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline Missing	32 Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 6 participants.

SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on ALT levels at baseline as assessed by investigator. Normal baseline ALT level was defined as \<40 IU/mL and elevated baseline ALT level was defined as \>= 40 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=286 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline Normal Baseline ALT levels	28 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline Elevated Baseline ALT levels	252 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline Missing	6 Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis.

SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on study treatment dosage modification: no dosage modification or any dosage modification of study treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=286 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification No Dosage Modification of Study Treatment	234 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification Any Dosage Modification of Study Treatment	52 Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 250 participants.

SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on achievement of rapid virological response (RVR) where data was available. RVR was defined as negative HCV-RNA after 4 (+/- 1) weeks of treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).

Outcome measures

Outcome measures
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=286 Participants Participants with Chronic Hepatitis C (CHC) of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype and viral load followed by a 24-week post-treatment follow-up.
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response RVR at Week 4 (+/- 1)	20 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response Non-RVR at Week 4 (+/- 1)	16 Participants
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response Missing	250 Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: No data had been captured in the Case Report Forms, and therefore no relevant analysis had been performed.

SVR was assessed by subgroups based on compliance with the 80/80/80 rule where data was available. 80/80/80 compliant participants were those that received \>= 80% of the planned total doses of both pegylated interferon alfa-2b \& ribavirin for \>=80% of the duration of therapy. 3 rates were to be computed: Compliance with study duration, compliance with pegylated interferon dose, \& compliance with ribavirin dose. A participant was defined as compliant, if none of the 3 rates were \< than 80%. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment.

Outcome measures

Outcome data not reported

Adverse Events

Pegylated Interferon Alpha-2b and Ribavirin

Serious events: 5 serious events

Other events: 123 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=401 participants at risk Participants with CHC of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on HCV genotype and viral load followed by a 24-week post-treatment follow-up.
Blood and lymphatic system disorders Anaemia	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
General disorders Oedema	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
General disorders Pain	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
General disorders Pyrexia	0.50% 2/401 • Number of events 2 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Infections and infestations Lung Infection	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Infections and infestations Pneumonia	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Infections and infestations Tooth Abscess	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Nervous system disorders Epilepsy	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Psychiatric disorders Emotional Disorder	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Skin and subcutaneous tissue disorders Erythema	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Vascular disorders Thrombophlebitis	0.25% 1/401 • Number of events 1 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).

Other adverse events

Other adverse events
Measure	Pegylated Interferon Alpha-2b and Ribavirin n=401 participants at risk Participants with CHC of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on HCV genotype and viral load followed by a 24-week post-treatment follow-up.
Blood and lymphatic system disorders Anaemia	15.2% 61/401 • Number of events 61 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Blood and lymphatic system disorders Leukopenia	7.7% 31/401 • Number of events 32 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
General disorders Fatigue	9.5% 38/401 • Number of events 41 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Investigations Weight Decreased	6.7% 27/401 • Number of events 27 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).
Skin and subcutaneous tissue disorders Alopecia	5.2% 21/401 • Number of events 21 The safety population included the total number of participants screened for eligibility (N=401). This population includes the total number of eligible participants enrolled in the study or the Full Analysis Set (N=332) and the non-eligible participants or the screening failure set (N=69).

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The principal investigator agrees not to publish or publicly present any interim results of the Study without prior written consent of the SPONSOR. The principal investigator further agrees to provide forty-five (45) days written notice to the SPONSOR prior to submission for publication or presentation to permit the SPONSOR to review copies of abstracts or manuscripts for publication which report any results of the Study. The SPONSOR shall have the right to review \& comment on any presentation.
Publication restrictions are in place

Restriction type: OTHER