Three Regimens of PegIntron Plus Ribavirin in Previously Untreated Chronic Hepatitis C, Genotype 2 or 3 (Study P03548AM2)(COMPLETED) - Study Results

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

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
696 subjects were randomized. 14 subjects never received any study drug and, therefore, were excluded from the Intent to Treat (ITT) population. ITT population consisted of 682 subjects.

Reporting Groups

	Description
PEG2b 1.5/R (24 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg daily for 24 weeks
PEG2b 1.0/R (24 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.0 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 24 weeks
PEG2b 1.5/R (16 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 16 weeks

Participant Flow: Overall Study

	PEG2b 1.5/R (24 Weeks)	PEG2b 1.0/R (24 Weeks)	PEG2b 1.5/R (16 Weeks)
STARTED	237	229	230
COMPLETED	181	186	178
NOT COMPLETED	56	43	52
Adverse Event	6	5	4
Lost to Follow-up	21	18	28
Withdrawal by Subject	8	12	8
Protocol Violation	5	1	2
Lack of Efficacy	1	0	5
Death	2	1	0
Other	13	6	5

Baseline Characteristics

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Reporting Groups

	Description
PEG2b 1.5/R (24 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg daily for 24 weeks
PEG2b 1.0/R (24 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.0 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 24 weeks
PEG2b 1.5/R (16 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 16 weeks

Baseline Measures

	PEG2b 1.5/R (24 Weeks)	PEG2b 1.0/R (24 Weeks)	PEG2b 1.5/R (16 Weeks)	Total
Number of Participants [units: participants]	230	224	228	682
Age [units: years] Mean ± Standard Deviation	38.8 ± 10.2	39.9 ± 11.2	39.7 ± 11.1	39.5 ± 10.9
Gender [units: participants]
Female	91	78	80	249
Male	139	146	148	433

Outcome Measures

1. Primary:

The Number of Participants Who Achieve a Sustained Virologic Response (SVR) [ 24-week treatment duration for Arms [Peg2b 1.5/R(24 weeks)] and [PEG2b 1.0/R(24 weeks]); 16-week treatment duration for Arm [PEG2b 1.5/R(16 weeks]. Follow-up of 24 weeks for each arm. ]

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Measure Type	Primary
Measure Title	The Number of Participants Who Achieve a Sustained Virologic Response (SVR)
Measure Description	A sustained virologic response is defined as undetectable hepatitis C virus ribonucleic acid [HCV-RNA] 24 weeks post-treatment. Serum HCV-RNA is measured by HCV-PCR in local laboratories. HCV-RNA below the limit of detection is considered undetectable.
Time Frame	24-week treatment duration for Arms [Peg2b 1.5/R(24 weeks)] and [PEG2b 1.0/R(24 weeks]); 16-week treatment duration for Arm [PEG2b 1.5/R(16 weeks]. Follow-up of 24 weeks for each arm.
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

Reporting Groups

	Description
PEG2b 1.5/R (24 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg daily for 24 weeks
PEG2b 1.0/R (24 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.0 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 24 weeks
PEG2b 1.5/R (16 Weeks)	PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 16 weeks

Measured Values

	PEG2b 1.5/R (24 Weeks)	PEG2b 1.0/R (24 Weeks)	PEG2b 1.5/R (16 Weeks)
Number of Participants Analyzed [units: participants]	230	224	228
The Number of Participants Who Achieve a Sustained Virologic Response (SVR) [units: participants]	153	144	129

Statistical Analysis 1 for The Number of Participants Who Achieve a Sustained Virologic Response (SVR)

Groups ^[1]	PEG2b 1.5/R (24 Weeks) vs. PEG2b 1.0/R (24 Weeks)
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	z-test (non-inferiority margin=-0.1)
P Value ^[4]	0.041
Risk Difference (RD) ^[5]	-0.02
95% Confidence Interval	( -0.10 to 1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	This is an evaluation of the effect of the peginterferon alfa-2b dose (1.0 vs 1.5 micrograms/kg/week) on the primary outcome measure.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Noninferiority for SVR was concluded if the lower limit of the one-sided 95% CI was greater than -10%. Otherwise, noninferiority was concluded for both dose and treatment duration comparisons if the lower limits of the two-sided 95% CIs were greater than -10%.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	SVR rates are 0.665 (153/230 subjects) in the 1.5-dose group and 0.643 (144/224 subjects) in the 1.0-dose group, for a risk difference of -0.02.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The Hochberg procedure was used to adjust for the multiple comparisons ([PEG2b 1.0/R(24 weeks)] - [PEG2b 1.5/R(24 weeks]) and ([PEG2b 1.5/R(16 weeks)]-[PEG2b 1.5/R(24 weeks)]).
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The Number of Participants Who Achieve a Sustained Virologic Response (SVR)

Groups ^[1]	PEG2b 1.5/R (24 Weeks) vs. PEG2b 1.5/R (16 Weeks)
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	z-test (non-inferiority margin=-0.1)
P Value ^[4]	0.495
Risk Difference (RD) ^[5]	-0.10
95% Confidence Interval	( -0.17 to 1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	This is an evaluation of the effect of treatment duration (24 weeks vs 16 weeks) on the primary outcome measure.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Noninferiority for SVR was concluded if the lower limit of the one-sided 95% CI was greater than -10%. Otherwise, noninferiority was concluded for both dose and treatment duration comparisons if the lower limits of the two-sided 95% CIs were greater than -10%.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	SVR rates are 0.665 (153/230 subjects) in the 24-week group and 0.566 (129/228 subjects) in the 16-week group, for a risk difference of -0.10.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The Hochberg procedure was used to adjust for the multiple comparisons ([PEG2b 1.0/R(24 weeks)] - [PEG2b 1.5/R(24 weeks]) and ([PEG2b 1.5/R(16 weeks]-[PEG2b 1.5/R(24 weeks]).
[5]	Other relevant estimation information:
	No text entered.

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
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Results Point of Contact:

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

No publications provided

Responsible Party:	Schering-Plough ( Head, Clinical Trials Registry & Results Disclosure Group )
Study ID Numbers:	P03548
Study First Received:	March 10, 2006
Results First Received:	April 29, 2009
Last Updated:	June 24, 2009
ClinicalTrials.gov Identifier:	NCT00302081 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices; Israel: Ministry of Health; India: Drugs Controller General of India; Poland: Ministry of Health; Indonesia: National Agency for Drug and Food Control; Singapore: Health Sciences Authority; Malaysia: Ministry of Health; Thailand: Thai Drug Control Division, Food and Drug Administration, Ministry of Public Health