Back to resultsSafety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED) (SPRINT-2)
Primary Purpose
Hepatitis C, Chronic
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Peginterferon alfa-2b (PEG)
Ribavirin (RBV)
Placebo
Boceprevir
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic
Eligibility Criteria
Inclusion Criteria:
- Participant must have previously documented CHC genotype 1 infection.
- Participant must have a liver biopsy with histology consistent with CHC and no other etiology.
- Participants with bridging fibrosis or cirrhosis must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma (HCC).
- Participant must be >=18 years of age.
- Participant must weigh between 40 kg and 125 kg.
- Participant and participant's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations.
- Participants must be willing to give written informed consent.
Exclusion Criteria:
- Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
- Participants who received prior treatment for hepatitis C; other than herbal remedies, except those with known hepatotoxicity.
- Treatment with any investigational drug within 30 days of the randomization visit in this study.
- Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study.
- Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.
- Diabetic and/or hypertensive participants with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality.
- Pre-existing psychiatric condition(s).
- Clinical diagnosis of substance abuse of the specified drugs within the specified timeframes.
- Any known pre-existing medical condition that could interfere with the participant's participation in and completion of the study.
- Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin). Participants under evaluation for malignancy are not eligible.
- Participants who are pregnant or nursing. Participants who intend to become pregnant during the study period. Male participants with partners who are, or intend to become, pregnant during the study period.
- Any other condition which, in the opinion of a physician, would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
- Participants who are part of the site personnel directly involved with this study.
- Participants who are family members of the investigational study staff.
- Participants who had life-threatening serious adverse event (SAE) during screening period.
- Protocol-specified hematologic, biochemical, and serologic criteria: Hemoglobin <12 g/dL for females and <13 g/dL for males; Neutrophils <1500/mm^3 (blacks: <1200/mm^3); Platelets <100,000/mm^3; Direct bilirubin >1.5 x upper limit of normal (ULN)
- Serum albumin < lower limit of normal (LLN)
- Thyroid-stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory, with certain exceptions.
- Serum creatinine >ULN of the laboratory reference.
- Protocol-specified serum glucose concentrations.
- protocol-specified alpha fetoprotein levels.
- Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above laboratory reference range.
- Anti-nuclear antibodies (ANA) >1:320.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
1. Placebo + PEG + RBV
2. Boceprevir + PEG + RBV - 24 Weeks (RGT)
3. Boceprevir + PEG + RBV - 44 Weeks
Arm Description
PegIntron (PEG) 1.5 μg/kg + Ribavirin (RBV) (weight-based dosing [WBD]) for 4 weeks (lead in treatment) followed by placebo + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
PEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 24 weeks. Participants were offered a response guided therapy (RGT) at treatment week 28. At the Treatment Week 28 visit, participants whose HCV-RNA was undetectable from Treatment Weeks 8 to Treatment Week 24, will proceed to the 44-week follow-up. At the Treatment Week 28 visit, participants with detectable HCV-RNA at Treatment Week 8 or at any subsequent assays will continue on therapy with placebo + PEG 1.5 μg/kg + RBV (WBD) for an additional 20 weeks, to complete a total of 48 weeks on treatment with 24 weeks post-treatment follow-up.
PEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
Outcomes
Primary Outcome Measures
Sustained Virologic Response (SVR) Rate
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate is the percent of participants achieving SVR.
HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have SVR.
Secondary Outcome Measures
Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo)
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate was the percentage of participants treated with at least one dose of boceprevir or placebo who had achieved SVR.
HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have a SVR.
Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. The number of participants who had undetectable plasma HCV-RNA at FW 12, and 72 weeks after randomization are reported.
HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20)
Early virologic response was defined as undetectable HCV-RNA at in participants by treatment week 2, 4, 8, 12, 16, or 20.
HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR
Participants with early virologic response were those who had undetectable HCV-RNA by treatment week 4, 8, 12, 16, or 20. Participants who had undetectable plasma HCV-RNA at FW 24 had SVR. The number of participants with early virologic response that also achieved SVR is reported.
HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00705432
Brief Title
Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED)
Acronym
SPRINT-2
Official Title
A Phase 3, Safety and Efficacy Study of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study involves treatment with boceprevir or placebo in combination with PegIntron (PEG) + Ribavirin (RBV) (weight-based dosing [WBD]) in previously untreated adult participants with chronic hepatitis C (CHC) genotype 1. It is hypothesized that the addition of a third active anti- Hepatitis C Virus (anti-HCV) drug may lead to more rapid viral response than therapy with two drugs, and therefore, the addition of boceprevir to PegIntron plus ribavirin therapy after a 4-week lead-in period may allow for both increased rates of sustained virologic response (SVR) and shorter treatment durations (in some populations) than treatment with PegIntron plus ribavirin alone.
The study includes two separate cohorts, Cohort I (White participants) and Cohort II (Black participants). Participants from each cohort are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV).
Detailed Description
Participants from Cohort I and Cohort II are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV).
Control arm, participants are treated with (PEG + RBV + placebo) for 44 weeks after the lead-in.
Experimental arm with Response Guided Therapy (RGT)
In this experimental arm, participants are treated with all three drugs (PEG + RBV + boceprevir) for 24 weeks after the lead-in. At treatment week 28, those participants with undetectable Hepatitis C Virus - ribonucleic acid (HCV-RNA) from week 8 (up to treatment week 24), will be considered to complete treatment, and will enter follow-up. Participants with detectable for HCV-RNA at week 8 or later will receive an additional 20 weeks of therapy with PegIntron and Ribavirin (PEG + RBV + placebo).
Experimental arm, participants are treated with all three drugs (PEG + RBV + Ribavirin) for 44 weeks after the lead-in.
All participants were followed up to 72 weeks following randomization.
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 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1472 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1. Placebo + PEG + RBV
Arm Type
Placebo Comparator
Arm Description
PegIntron (PEG) 1.5 μg/kg + Ribavirin (RBV) (weight-based dosing [WBD]) for 4 weeks (lead in treatment) followed by placebo + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
Arm Title
2. Boceprevir + PEG + RBV - 24 Weeks (RGT)
Arm Type
Experimental
Arm Description
PEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 24 weeks. Participants were offered a response guided therapy (RGT) at treatment week 28.
At the Treatment Week 28 visit, participants whose HCV-RNA was undetectable from Treatment Weeks 8 to Treatment Week 24, will proceed to the 44-week follow-up.
At the Treatment Week 28 visit, participants with detectable HCV-RNA at Treatment Week 8 or at any subsequent assays will continue on therapy with placebo + PEG 1.5 μg/kg + RBV (WBD) for an additional 20 weeks, to complete a total of 48 weeks on treatment with 24 weeks post-treatment follow-up.
Arm Title
3. Boceprevir + PEG + RBV - 44 Weeks
Arm Type
Experimental
Arm Description
PEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
Intervention Type
Biological
Intervention Name(s)
Peginterferon alfa-2b (PEG)
Other Intervention Name(s)
PegIntron, PEG, SCH 54031
Intervention Description
Peginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)
Intervention Type
Drug
Intervention Name(s)
Ribavirin (RBV)
Other Intervention Name(s)
Rebetol, RBV, SCH 18908
Intervention Description
Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day administered orally, divided twice daily (BID).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to boceprevir, 800 mg (4 x 200mg capsules) administered orally three times a day (TID).
Intervention Type
Drug
Intervention Name(s)
Boceprevir
Other Intervention Name(s)
SCH 503034, Victrelis
Intervention Description
Boceprevir, 800 mg (4 x 200 mg capsules) administered orally TID.
Primary Outcome Measure Information:
Title
Sustained Virologic Response (SVR) Rate
Description
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate is the percent of participants achieving SVR.
HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have SVR.
Time Frame
At Follow-up Week (FW) 24
Secondary Outcome Measure Information:
Title
Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo)
Description
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate was the percentage of participants treated with at least one dose of boceprevir or placebo who had achieved SVR.
HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have a SVR.
Time Frame
At FW 24
Title
Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.
Description
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. The number of participants who had undetectable plasma HCV-RNA at FW 12, and 72 weeks after randomization are reported.
HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
Time Frame
At FW 12 and at 72 weeks after randomization
Title
Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20)
Description
Early virologic response was defined as undetectable HCV-RNA at in participants by treatment week 2, 4, 8, 12, 16, or 20.
HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
Time Frame
At Treatment Week 2, 4, 8, 12, 16, or 20
Title
Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR
Description
Participants with early virologic response were those who had undetectable HCV-RNA by treatment week 4, 8, 12, 16, or 20. Participants who had undetectable plasma HCV-RNA at FW 24 had SVR. The number of participants with early virologic response that also achieved SVR is reported.
HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
Time Frame
At Treatment Week 4, 8, 12, 16, 20
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must have previously documented CHC genotype 1 infection.
Participant must have a liver biopsy with histology consistent with CHC and no other etiology.
Participants with bridging fibrosis or cirrhosis must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma (HCC).
Participant must be >=18 years of age.
Participant must weigh between 40 kg and 125 kg.
Participant and participant's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations.
Participants must be willing to give written informed consent.
Exclusion Criteria:
Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
Participants who received prior treatment for hepatitis C; other than herbal remedies, except those with known hepatotoxicity.
Treatment with any investigational drug within 30 days of the randomization visit in this study.
Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study.
Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.
Diabetic and/or hypertensive participants with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality.
Pre-existing psychiatric condition(s).
Clinical diagnosis of substance abuse of the specified drugs within the specified timeframes.
Any known pre-existing medical condition that could interfere with the participant's participation in and completion of the study.
Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin). Participants under evaluation for malignancy are not eligible.
Participants who are pregnant or nursing. Participants who intend to become pregnant during the study period. Male participants with partners who are, or intend to become, pregnant during the study period.
Any other condition which, in the opinion of a physician, would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
Participants who are part of the site personnel directly involved with this study.
Participants who are family members of the investigational study staff.
Participants who had life-threatening serious adverse event (SAE) during screening period.
Protocol-specified hematologic, biochemical, and serologic criteria: Hemoglobin <12 g/dL for females and <13 g/dL for males; Neutrophils <1500/mm^3 (blacks: <1200/mm^3); Platelets <100,000/mm^3; Direct bilirubin >1.5 x upper limit of normal (ULN)
Serum albumin < lower limit of normal (LLN)
Thyroid-stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory, with certain exceptions.
Serum creatinine >ULN of the laboratory reference.
Protocol-specified serum glucose concentrations.
protocol-specified alpha fetoprotein levels.
Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above laboratory reference range.
Anti-nuclear antibodies (ANA) >1:320.
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
23621902
Citation
Ferrante SA, Chhatwal J, Brass CA, El Khoury AC, Poordad F, Bronowicki JP, Elbasha EH. Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study. BMC Infect Dis. 2013 Apr 27;13:190. doi: 10.1186/1471-2334-13-190.
Results Reference
derived
PubMed Identifier
22626609
Citation
Poordad F, Bronowicki JP, Gordon SC, Zeuzem S, Jacobson IM, Sulkowski MS, Poynard T, Morgan TR, Molony C, Pedicone LD, Sings HL, Burroughs MH, Sniukiene V, Boparai N, Goteti VS, Brass CA, Albrecht JK, Bacon BR; SPRINT-2 and RESPOND-2 Investigators. Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology. 2012 Sep;143(3):608-618.e5. doi: 10.1053/j.gastro.2012.05.011. Epub 2012 May 21.
Results Reference
derived
PubMed Identifier
21449783
Citation
Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1195-206. doi: 10.1056/NEJMoa1010494.
Results Reference
derived
Learn more about this trial
Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED)
We'll reach out to this number within 24 hrs