Peginterferon Dose Evaluations for Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03471AM1)(COMPLETED) - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Dose Comparison, Parallel Assignment
Condition:	Hepatitis C, Chronic
Interventions:	Biological: PegIntron (peginterferon alfa-2b; SCH 54031) Drug: REBETOL (ribavirin; SCH 18908) Biological: PEGASYS (peginterferon alfa-2a) Drug: COPEGUS (ribavirin)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolled 4469 subjects; Randomized 3083; Treated 3070

Reporting Groups

	Description
PegIntron 1.5 ug/kg/wk Plus REBETOL	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up
PegIntron 1.0 ug/kg/wk Plus REBETOL	PegIntron (peginterferon alfa-2b; SCH 54031) 1.0 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up
PEGASYS 180 ug/wk Plus COPEGUS	PEGASYS (peginterferon alfa-2a) 180 ug/week plus COPEGUS (ribavirin) 1000-1200 mg/day administered for 48 weeks with 24-week post-treatment follow-up

Participant Flow: Overall Study

	PegIntron 1.5 ug/kg/wk Plus REBETOL	PegIntron 1.0 ug/kg/wk Plus REBETOL	PEGASYS 180 ug/wk Plus COPEGUS
STARTED	1019	1016	1035
COMPLETED	517^[1]	470^[2]	579^[3]
NOT COMPLETED	502	546	456
Adverse Event	130	98	136
Lack of Efficacy	262	357	211
Lost to Follow-up	45	34	45
Protocol Violation	15	10	10
Withdrawal by Subject	45	40	42
Did not meet protocol eligibility	2	0	3
Administrative	1	0	1
Not Specified	2	7	8

[1]	Patients who discontinued treatment but continued in study are considered Not Completed
[2]	Patients who discontinued treatment but continued in study are considered Not Completed
[3]	Patients who discontinued treatment but continued in study are considered Not Completed

Baseline Characteristics

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Reporting Groups

	Description
PegIntron 1.5 ug/kg/wk Plus REBETOL	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up
PegIntron 1.0 ug/kg/wk Plus REBETOL	PegIntron (peginterferon alfa-2b; SCH 54031) 1.0 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up
PEGASYS 180 ug/wk Plus COPEGUS	PEGASYS (peginterferon alfa-2a) 180 ug/week plus COPEGUS (ribavirin) 1000-1200 mg/day administered for 48 weeks with 24-week post-treatment follow-up

Baseline Measures

	PegIntron 1.5 ug/kg/wk Plus REBETOL	PegIntron 1.0 ug/kg/wk Plus REBETOL	PEGASYS 180 ug/wk Plus COPEGUS	Total
Number of Participants [units: participants]	1019	1016	1035	3070
Age [units: years] Mean ± Standard Deviation	47.5 ± 7.8	47.5 ± 8.1	47.6 ± 8.2	47.5 ± 8.0
Gender [units: participants]
Female	406	409	422	1237
Male	613	607	613	1833

Outcome Measures

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1. Primary:

Sustained Virologic Response (SVR) Rate [ Assessed at the end of a 24-week post-treatment follow-up ]

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Measure Type	Primary
Measure Title	Sustained Virologic Response (SVR) Rate
Measure Description	SVR rate is the proportion of subjects with undetectable hepatitis C virus ribonucleic acid (HCV-RNA) at the end of the 24-week post-treatment follow-up.
Time Frame	Assessed at the end of a 24-week post-treatment follow-up
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat [ITT] Population defined as subjects who received at least one dose of study medication

Reporting Groups

	Description
PegIntron 1.5 ug/kg/wk Plus REBETOL	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up
PegIntron 1.0 ug/kg/wk Plus REBETOL	PegIntron (peginterferon alfa-2b; SCH 54031) 1.0 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up
PEGASYS 180 ug/wk Plus COPEGUS	PEGASYS (peginterferon alfa-2a) 180 ug/week plus COPEGUS (ribavirin) 1000-1200 mg/day administered for 48 weeks with 24-week post-treatment follow-up

Measured Values

	PegIntron 1.5 ug/kg/wk Plus REBETOL	PegIntron 1.0 ug/kg/wk Plus REBETOL	PEGASYS 180 ug/wk Plus COPEGUS
Number of Participants Analyzed [units: participants]	1019	1016	1035
Sustained Virologic Response (SVR) Rate [units: Percentage of participants]	39.8	38.0	40.9

Statistical Analysis 1 for Sustained Virologic Response (SVR) Rate

Groups ^[1]	PegIntron 1.5 ug/kg/wk Plus REBETOL vs. PEGASYS 180 ug/wk Plus COPEGUS
Method ^[2]	Regression, Logistic
P Value ^[3]	0.567
Odds Ratio (OR) ^[4]	0.95
95% Confidence Interval	( 0.79 to 1.14 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	The p-value is based on the logistic regression model that includes treatment and baseline stratification factors (viral load and race).
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Holm’s method for multiplicity adjustment was to be used to control the overall Type I error rate at α = 0.05. However, since there was no significant difference in the overall SVR rates between the three groups, no Type-1 error adjustment was made.
[4]	Other relevant estimation information:
	The odds ratio is based on the logistic regression model that includes treatment and baseline stratification factors: viral load (≤600,000 IU/mL vs >600,000 IU/mL) and race (Black vs non-Black).

Statistical Analysis 2 for Sustained Virologic Response (SVR) Rate

Groups ^[1]	PegIntron 1.5 ug/kg/wk Plus REBETOL vs. PegIntron 1.0 ug/kg/wk Plus REBETOL
Method ^[2]	Regression, Logistic
P Value ^[3]	0.195
Odds Ratio (OR) ^[4]	1.08
95% Confidence Interval	( 0.90 to 1.30 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	The p-value is based on the logistic regression model that includes treatment and baseline stratification factors (viral load and race).
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Holm’s method for multiplicity adjustment was to be used to control the overall Type I error rate at α = 0.05. However, since there was no significant difference in the overall SVR rates between the three groups, no Type-1 error adjustment was made.
[4]	Other relevant estimation information:
	The odds ratio is based on the logistic regression model that includes treatment and baseline stratification factors: viral load (≤600,000 IU/mL vs >600,000 IU/mL) and race (Black vs non-Black).

2. Secondary:

Mean Change From Baseline in the Log Viral Load at Treatment Week 4 [ Assessed at Baseline and Treatment Week 4 ]

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3. Secondary:

Virologic Response Rate at Treatment Week 12 [ Assessed at Treatment Week 12 ]

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4. Secondary:

Mean Change From Baseline in the Log Viral Load at Treatment Week 2 [ Assessed at Baseline and Treatment Week 2 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Head, Clinical Trials Registry & Results Disclosure Group
Organization: Schering-Plough
e-mail: ClinicalTrialsDisclosure@spcorp.com

Publications of Results:

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009 Aug 6;361(6):580-93. Epub 2009 Jul 22.

Responsible Party:	Schering-Plough ( Head, Clinical Trials Registry & Results Disclosure Group )
Study ID Numbers:	P03471, 2552898
Study First Received:	April 20, 2004
Results First Received:	November 3, 2008
Last Updated:	September 24, 2009
ClinicalTrials.gov Identifier:	NCT00081770 History of Changes
Health Authority:	United States: Food and Drug Administration