Safety and Efficacy of SCH 503034 in Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03523AM2) (COMPLETED)

This study has been completed.

Sponsor:

Information provided by:

Merck

ClinicalTrials.gov Identifier:

NCT00423670

First received: January 17, 2007

Last updated: March 15, 2013

Last verified: March 2013

History of Changes

Results First Received: May 13, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Chronic Hepatitis C
Interventions:	Drug: boceprevir (SCH 503034) Drug: peginterferon-alfa 2b (PegIntron) Drug: ribavirin Drug: ribavirin (low-dose)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
765 participants were screened in the study, 598 were randomized of which 3 participants were not treated (Arm 1-7). Participants were assigned to Part I (with standard dosing for ribavirin) or Part II (to explore low-dose ribavirin). All participants that completed or discontinued treatment were scheduled to enter follow-up phase per protocol.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants in Arm 1 (Part I) who had detectable Hepatitis C Virus-ribonucleic acid (HCV-RNA) at Treatment Week (TW) 24 were offered boceprevir in addition to PegIntron and ribavirin for an additional 24 weeks of treatment, and switched to a new arm, Arm 8.

Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg, once weekly [QW]) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg, thrice a day [TID]) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)	Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.

Participant Flow for 2 periods

Period 1: Treatment Period

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)
STARTED	104	107	103	103	103	16	59	36 ^[1]
COMPLETED	52	77	76	63	76	8	28	15
NOT COMPLETED	52	30	27	40	27	8	31	21
Switched to Arm 8 at TW 24	36	0	0	0	0	0	0	0
Adverse Event	8	12	15	20	9	4	7	2
Protocol-defined clinical event	0	7	4	12	5	4	16	15
Lost to Follow-up	2	1	3	1	6	0	3	1
Subject withdrew (not treatment related)	3	9	4	4	5	0	3	0
Investigator decision	0	0	0	0	0	0	0	1
Non-compliance with protocol	3	1	1	3	2	0	2	2

[1]	Arm 8 were Arm 1 participants that were positive for HCV-RNA at TW 24 and had the option to switch.

Period 2: Follow-up Period

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)
STARTED	97	100	96	96	91	14	50	35
COMPLETED	94	84	85	91	89	14	41	32
NOT COMPLETED	3	16	11	5	2	0	9	3
Lost to Follow-up	0	12	8	3	1	0	5	0
Subject withdrew (not treatment related)	1	4	2	1	1	0	1	1
Non-compliance with protocol	2	0	1	1	0	0	3	2

Baseline Characteristics

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Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Total	Total of all reporting groups

Baseline Measures

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	Total
Number of Participants [units: participants]	104	107	103	103	103	16	59	595
Age ^[1] [units: years] Mean ± Standard Deviation	48.3 ± 6.9	46.4 ± 8.0	47.7 ± 7.4	46.7 ± 8.8	47.6 ± 8.3	50.3 ± 8.5	48.7 ± 5.8	47.5 ± 7.7
Gender ^[2] [units: participants]
Female	34	44	52	40	45	7	18	240
Male	70	63	51	63	58	9	41	355

[1]	Overall age characteristics were displayed for Arm 1 through Arm 7. Participants from Arm 1 (Part I) who had detectable HCV-RNA at TW 24, had the option to switch to a new arm, Arm 8.
[2]	Overall gender characteristics were displayed for Arm 1 through Arm 7. Participants from Arm 1 (Part I) who had detectable HCV-RNA TW 24, had the option to switch to a new arm, Arm 8.

Outcome Measures

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1. Primary:

Number of Participants With Sustained Virologic Response (SVR) [ Time Frame: From follow-up week (FW) 24 up to end of follow-up (EOF) ]

Measure Type	Primary
Measure Title	Number of Participants With Sustained Virologic Response (SVR)
Measure Description	Participants with undetectable HCV-RNA at FW 24 up to EOF had achieved SVR. Participants missing data at FW 24 were considered to achieve SVR if he/she had undetectable HCV-RNA at FW 12 or later he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with reverse-transcriptase-polymerase chain reaction (RT-PCR) assay, with a lower limit of detection (LLD) of 29 international units/mL (IU/mL). A participant in Arm 2 with undetectable HCV-RNA at FW 24 had detectable HCV-RNA after FW 24. He is not considered to achieve SVR.
Time Frame	From follow-up week (FW) 24 up to end of follow-up (EOF)
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: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).

Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.

Measured Values

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Number of Participants Analyzed [units: participants]	104	107	103	103	103	16	59
Number of Participants With Sustained Virologic Response (SVR) [units: Participants]	39	58	58	69	77	8	21

Statistical Analysis 1 for Number of Participants With Sustained Virologic Response (SVR)

Groups ^[1]	Arm 1. PEG +RBV for 48 Wks (Part I) vs. Arm 2. PEG + RBV + BOC for 28 Wks (Part I)
Method ^[2]	Cochran-Mantel Haenszel Chi-square test
P Value ^[3]	0.0126
Percent difference in SVR ^[4]	16.7
95% Confidence Interval	( 3.5 to 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:
	Adjusted for baseline stratification factors: black versus non-black, and cirrhosis versus no cirrhosis.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Number of Participants With Sustained Virologic Response (SVR)

Groups ^[1]	Arm 1. PEG +RBV for 48 Wks (Part I) vs. Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)
Method ^[2]	Cochran-Mantel Haenszel Chi-square test
P Value ^[3]	0.0048
Percent difference in SVR ^[4]	18.8
95% Confidence Interval	( 5.5 to 32.2 )

[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:
	Adjusted for baseline stratification factors: black versus non-black, and cirrhosis versus no cirrhosis.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Number of Participants With Sustained Virologic Response (SVR)

Groups ^[1]	Arm 1. PEG +RBV for 48 Wks (Part I) vs. Arm 4. PEG +RBV + BOC for 48 Wks (Part I)
Method ^[2]	Cochran-Mantel Haenszel Chi-square test
P Value ^[3]	<0.0001
Percent difference in SVR ^[4]	29.5
95% Confidence Interval	( 16.5 to 42.5 )

[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:
	Adjusted for baseline stratification factors: black versus non-black, and cirrhosis versus no cirrhosis.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Number of Participants With Sustained Virologic Response (SVR)

Groups ^[1]	Arm 1. PEG +RBV for 48 Wks (Part I) vs. Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)
Method ^[2]	Cochran-Mantel Haenszel Chi-square test
P Value ^[3]	<0.0001
Percent difference in SVR ^[4]	37.3
95% Confidence Interval	( 24.7 to 49.8 )

[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:
	Adjusted for baseline stratification factors: black versus non-black, and cirrhosis versus no cirrhosis.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

2. Secondary:

Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin [ Time Frame: From FW 24 up to EOF ]

Measure Type	Secondary
Measure Title	Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin
Measure Description	Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). To assess the effect of lead-in treatment on SVR, participants with (Arm 3 and Arm 5) or without (Arm 2 and Arm 4) lead-in were pooled. Participants missing data at FW 24 were considered to achieve SVR if he/she had undetectable HCV-RNA at FW 12 or later he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time Frame	From FW 24 up to EOF
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: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).

Reporting Groups

	Description
Arm 3 and Arm 5. PEG + RBV + BOC (From Wk 4)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 2 and Arm 4. PEG + RBV + BOC	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.

Measured Values

	Arm 3 and Arm 5. PEG + RBV + BOC (From Wk 4)	Arm 2 and Arm 4. PEG + RBV + BOC
Number of Participants Analyzed [units: participants]	206	210
Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin [units: Participants]	135	127

Statistical Analysis 1 for Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin

Groups ^[1]	All groups
Method ^[2]	Cochran-Mantel-Haenszel Chi-Square Test
P Value ^[3]	0.2864
Percent difference in SVR rates ^[4]	5.1
95% Confidence Interval	( -4.2 to 14.3 )

[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:
	Adjusted for baseline stratification factors: black versus non black, and cirrhosis versus no cirrhosis.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

3. Secondary:

Number of Participants With SVR Based on Duration of Boceprevir Treatment [ Time Frame: From FW 24 up to EOF ]

Measure Type	Secondary
Measure Title	Number of Participants With SVR Based on Duration of Boceprevir Treatment
Measure Description	Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). Participants from treatment arms receiving boceprevir for 28-weeks (Arm 2 and Arm 3) were pooled, and those receiving boceprevir for 48-weeks (Arm 4 and Arm 5) were pooled for the analysis. Participants missing data at FW 24 were considered to achieve SVR if he/she had undetectable HCV-RNA at FW 12 or later he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time Frame	From FW 24 up to EOF
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: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).

Reporting Groups

	Description
Arm 4 and Arm 5. PEG + RBV + BOC (48 Weeks)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) with or without a 4 weeks lead with boceprevir (800 mg TID) for 48 weeks.
Arm 2 and Arm 3. PEG + RBV + BOC (28 Weeks)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) with or without a 4 weeks lead with boceprevir (800 mg TID) for 28 weeks.

Measured Values

	Arm 4 and Arm 5. PEG + RBV + BOC (48 Weeks)	Arm 2 and Arm 3. PEG + RBV + BOC (28 Weeks)
Number of Participants Analyzed [units: participants]	206	210
Number of Participants With SVR Based on Duration of Boceprevir Treatment [units: Participants]	146	116

Statistical Analysis 1 for Number of Participants With SVR Based on Duration of Boceprevir Treatment

Groups ^[1]	All groups
Method ^[2]	Cochran-Mantel-Haenszel Chi-Square Test
P Value ^[3]	0.0009
Percent difference in SVR rates ^[4]	15.6
95% Confidence Interval	( 6.5 to 24.8 )

[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:
	Adjusted for the baseline stratification factors: black versus non black, and cirrhosis versus no cirrhosis.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

4. Secondary:

Number of Participants Negative for HCV-RNA at FW 12 [ Time Frame: At FW 12 ]

Measure Type	Secondary
Measure Title	Number of Participants Negative for HCV-RNA at FW 12
Measure Description	Participants who had undetectable plasma HCV-RNA at FW 12. Also reported are participants for whom the HCV-RNA values were missing. 36 participant who switched over to Arm 8 from Arm 1, are included in the missing values for Arm 1. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time Frame	At FW 12
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: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).

Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.

Measured Values

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Number of Participants Analyzed [units: participants]	104	107	103	103	103	16	59
Number of Participants Negative for HCV-RNA at FW 12 [units: Participants]
HCV-RNA negative	39	60	59	69	76	8	21
Missing HCV-RNA at FW 12	42	13	11	12	14	2	17

No statistical analysis provided for Number of Participants Negative for HCV-RNA at FW 12

5. Secondary:

Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization [ Time Frame: 72 weeks post randomization ]

Measure Type	Secondary
Measure Title	Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization
Measure Description	Participants who had undetectable HCV-RNA at 72 weeks post randomization are reported. Participants with missing HCV-RNA values at 72 weeks post randomization are also reported. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time Frame	72 weeks post randomization
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.
No text entered.

Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.

Measured Values

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Number of Participants Analyzed [units: participants]	104	107	103	103	103	16	59
Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization [units: Participants]
HCV-RNA negative	38	53	56	67	76	8	20
Missing HCV-RNA at 72 weeks post randomization	45	25	18	17	20	6	22

No statistical analysis provided for Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization

6. Secondary:

Number of Participants With an Early Virologic Response (EVR) That Achieved SVR [ Time Frame: At TW 12, and at FW 24 up to EOF ]

Measure Type	Secondary
Measure Title	Number of Participants With an Early Virologic Response (EVR) That Achieved SVR
Measure Description	Participants with undetectable HCV-RNA at TW 12 have EVR, and with undetectable HCV-RNA at FW 24 (up to EOF) achieved SVR. Participants missing data at FW 24 were considered to achieve SVR if he/she had undetectable HCV-RNA at FW 12 or later if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time Frame	At TW 12, and at FW 24 up to EOF
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.
Participants with an early virologic response (EVR).

Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.

Measured Values

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Number of Participants Analyzed [units: participants]	37	85	85	81	85	11	35
Number of Participants With an Early Virologic Response (EVR) That Achieved SVR [units: Participants]	32	58	58	68	77	8	21

No statistical analysis provided for Number of Participants With an Early Virologic Response (EVR) That Achieved SVR

7. Secondary:

Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR [ Time Frame: At FW 12 and FW 24 up to EOF ]

Measure Type	Secondary
Measure Title	Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR
Measure Description	Treatment-naïve adults with CHC genotype 1 were assigned study medication. Participants with undetectable HCV-RNA at FW 12 that achieved SVR (have undetectable HCV-RNA at FW 24 (up to EOF) are reported. Participants missing data at FW 24 were considered to achieve SVR if he/she had undetectable HCV-RNA at FW 12 or later if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time Frame	At FW 12 and FW 24 up to EOF
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.
Participants with undetectable HCV-RNA at FW 12.

Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.

Measured Values

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Number of Participants Analyzed [units: participants]	39	60	59	69	76	8	21
Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR [units: Participants]
HCV-RNA negative at EOF	39	58	58	69	76	8	20
HCV-RNA positive at EOF	0	2	1	0	0	0	1
Missing HCV-RNA at EOF	0	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR

8. Secondary:

Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR [ Time Frame: At FW 24 up to EOF and at 72 weeks post randomization ]

Measure Type	Secondary
Measure Title	Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR
Measure Description	Participants with undetectable HCV-RNA at 72 weeks post randomization that achieved SVR (have undetectable HCV-RNA at FW 24 up to EOF) are reported. Participants missing data at FW 24 were considered to achieve SVR if he/she had undetectable HCV-RNA at FW 12 or later if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected an the RT-PCR assay. The lower limit of detection (LLD) was 29 IU/mL.
Time Frame	At FW 24 up to EOF and at 72 weeks post randomization
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.
Participants who achieved SVR.

Reporting Groups

	Description
Arm 1. PEG +RBV for 48 Wks (Part I)	PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks. • Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.
Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)	PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.

Measured Values

	Arm 1. PEG +RBV for 48 Wks (Part I)	Arm 2. PEG + RBV + BOC for 28 Wks (Part I)	Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)	Arm 4. PEG +RBV + BOC for 48 Wks (Part I)	Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)	Arm 6. PEG + RBV + BOC for 48 Wks (Part II)	Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)
Number of Participants Analyzed [units: participants]	39	58	58	69	77	8	21
Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR [units: Participants]
HCV-RNA negative at 72 weeks post randomization	38	53	56	67	76	8	20
HCV-RNA positive at FW 24	0	0	0	0	0	0	0
Missing HCV-RNA at 72 weeks post randomization	1	5	2	2	1	0	1

No statistical analysis provided for Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR

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. Restriction Description: The Principal Investigator agrees to provide to the sponsor thirty (30) days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including slides and texts of oral or other public presentations and texts of any transmission through any electronic media) that report any results of the study.

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: Vice President, Late Stage Development Group Leader
Organization: Merck, Sharp and Dohme
e-mail: ClinicalTrialsDisclosure@merck.com

No publications provided by Merck

Publications automatically indexed to this study:

Kwo PY, Lawitz EJ, McCone J, Schiff ER, Vierling JM, Pound D, Davis MN, Galati JS, Gordon SC, Ravendhran N, Rossaro L, Anderson FH, Jacobson IM, Rubin R, Koury K, Pedicone LD, Brass CA, Chaudhri E, Albrecht JK. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010 Aug 28;376(9742):705-16. Epub 2010 Aug 6.

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme
ClinicalTrials.gov Identifier:	NCT00423670 History of Changes
Other Study ID Numbers:	P03523, EudraCT No. 2006-002543-92
Study First Received:	January 17, 2007
Results First Received:	May 13, 2011
Last Updated:	March 15, 2013
Health Authority:	United States: Food and Drug Administration

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