Evaluation of Peginterferon Alfa-2b Monotherapy and Combination With Ribavirin in Participants With Acute Hepatitis C (P03552/MK-4031-137)
Primary Purpose
Hepatitis C
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Pegylated interferon alfa-2b
Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C
Eligibility Criteria
Inclusion Criteria:
- Diagnosed with acute hepatitis C virus (HCV).
- Normal and Elevated serum alanine transferase (ALT) levels
- Positive serum HCV-RNA.
- Aged between 18 and 65 years.
- Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of the drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and additionally for participants treated with ribavirin, for 6 months (for woman) and 7 months (for man and his partner) after treatment completion
Exclusion Criteria:
- Liver disease unrelated to HCV infection
- Hemoglobin (Hgb) <12g/dL in women and <13g/dL in men; white blood cells (WBC) <3,000/uL; platelets (PLTs) <100,000/ul
- Women with ongoing pregnancy or who are breast feeding
- History of severe psychiatric disease, especially depression
- History of neurologic disease, especially epilepsy
- History or evidence of symptoms of severe cardiac, gastrointestinal and kidney disease
- Positive anti-Human Immunodeficiency Virus (HIV) antibodies
- Positive anti-nuclear antibodies (ANA) and/or Anti-Smooth Muscle Antibody (ASMA) (>1/80)
- Positive Hepatitis B surface antigen (HBsAg)
- History of having received any systemic anti-neoplastic or immunomodulatory treatment in the previous 6 months
- History or other evidence of severe illness or any other conditions which would make the participants, in the opinion of investigator, unsuitable for the study (active drug addict except those under methadone treatment, thalassemic, dyalized included)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
PEG-IFN 24
PEG-IFN 12
PEG-IFN + RVB 12
Arm Description
pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin at the dose of 10.6 mg/kg/day for 12 weeks
Outcomes
Primary Outcome Measures
Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period
SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL.
Secondary Outcome Measures
Virologic Response at the End of Treatment Follow-up (ETR)
ETR was achieved if serum HCV RNA level at the end of 12 or 24 weeks
treatment (depending on treatment arm) was <15 IU/mL.
Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]).
LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was <15 IU/mL.
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization
ALT normalization was used as a measure of biochemical response to treatment. ALT levels were assessed at each study visit by the local laboratory, and efficacy measurements at the end of treatment, at 6 and 12 months post treatment follow-up were reported.
Number of Participants With Rapid Virologic Response (RVR)
Participants were considered to have RVR if serum HCV RNA level at 2 or 4
weeks of treatment was below the cut off value of the referring local
laboratory of each participating site.
Number of Peripheral Blood Mononuclear Cells (PBMCs)
Cellular Differentiation Cluster Antigen 8-Positive (CD8+) PBMCs were measured at randomization, Treatment Weeks 2, 4, 8, and 12.
Full Information
NCT ID
NCT00686517
First Posted
May 27, 2008
Last Updated
March 8, 2017
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Bioikos Ambiente Srl
1. Study Identification
Unique Protocol Identification Number
NCT00686517
Brief Title
Evaluation of Peginterferon Alfa-2b Monotherapy and Combination With Ribavirin in Participants With Acute Hepatitis C (P03552/MK-4031-137)
Official Title
An Open, Randomized, Multicentre Trial to Evaluate Efficacy and Safety of a 24-week Course of PEG-Interferon Alpha-2b Versus a 12-week Course of PEG-Interferon Alpha-2b Alone or Plus Ribavirin in Patients With Acute Hepatitis C
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Bioikos Ambiente Srl
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this study is to evaluate the efficacy of three regimens of pegylated interferon-alfa 2b (PEG-IFN) either as monotherapy or in combination with ribavirin in participants with acute hepatitis C. After 12 weeks of observation from disease onset, participants will receive one of the following regimens: (1) a 24-week course of PEG-IFN monotherapy (PEG-IFN 24); or (2) a 12-week course of PEG-IFN monotherapy (PEG-IFN-12); or (3) a 12-week course of PEG-IFN in combination with ribavirin (PEG-IFN + RVB 12). After the treatment period, participants will enter a 12-month follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PEG-IFN 24
Arm Type
Experimental
Arm Description
pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
Arm Title
PEG-IFN 12
Arm Type
Experimental
Arm Description
pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
Arm Title
PEG-IFN + RVB 12
Arm Type
Experimental
Arm Description
pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin at the dose of 10.6 mg/kg/day for 12 weeks
Intervention Type
Biological
Intervention Name(s)
Pegylated interferon alfa-2b
Other Intervention Name(s)
SCH 54031, PegIntron
Intervention Description
1.5 ug/kg/week SC for 12 or 24 weeks
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
SCH 18908, Rebetol
Intervention Description
Ribavirin at the dose of 10.6 mg/kg/day for 12 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period
Description
SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL.
Time Frame
Evaluated at the end of 6 months
Secondary Outcome Measure Information:
Title
Virologic Response at the End of Treatment Follow-up (ETR)
Description
ETR was achieved if serum HCV RNA level at the end of 12 or 24 weeks
treatment (depending on treatment arm) was <15 IU/mL.
Time Frame
At the end of treatment (either 12 weeks or 24 weeks depending on randomization).
Title
Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]).
Description
LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was <15 IU/mL.
Time Frame
At 12 months post-treatment (treatment period either 12 weeks or 24 weeks depending on randomization).
Title
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization
Description
ALT normalization was used as a measure of biochemical response to treatment. ALT levels were assessed at each study visit by the local laboratory, and efficacy measurements at the end of treatment, at 6 and 12 months post treatment follow-up were reported.
Time Frame
Evaluated at end of treatment (either 12 weeks or 24 weeks, depending on randomization), at 6-month follow-up visit, or at 12-month follow-up visit.
Title
Number of Participants With Rapid Virologic Response (RVR)
Description
Participants were considered to have RVR if serum HCV RNA level at 2 or 4
weeks of treatment was below the cut off value of the referring local
laboratory of each participating site.
Time Frame
Evaluated at 2 and 4 weeks of treatment
Title
Number of Peripheral Blood Mononuclear Cells (PBMCs)
Description
Cellular Differentiation Cluster Antigen 8-Positive (CD8+) PBMCs were measured at randomization, Treatment Weeks 2, 4, 8, and 12.
Time Frame
Treatment Weeks 2, 4, 8, and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed with acute hepatitis C virus (HCV).
Normal and Elevated serum alanine transferase (ALT) levels
Positive serum HCV-RNA.
Aged between 18 and 65 years.
Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of the drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and additionally for participants treated with ribavirin, for 6 months (for woman) and 7 months (for man and his partner) after treatment completion
Exclusion Criteria:
Liver disease unrelated to HCV infection
Hemoglobin (Hgb) <12g/dL in women and <13g/dL in men; white blood cells (WBC) <3,000/uL; platelets (PLTs) <100,000/ul
Women with ongoing pregnancy or who are breast feeding
History of severe psychiatric disease, especially depression
History of neurologic disease, especially epilepsy
History or evidence of symptoms of severe cardiac, gastrointestinal and kidney disease
Positive anti-Human Immunodeficiency Virus (HIV) antibodies
Positive anti-nuclear antibodies (ANA) and/or Anti-Smooth Muscle Antibody (ASMA) (>1/80)
Positive Hepatitis B surface antigen (HBsAg)
History of having received any systemic anti-neoplastic or immunomodulatory treatment in the previous 6 months
History or other evidence of severe illness or any other conditions which would make the participants, in the opinion of investigator, unsuitable for the study (active drug addict except those under methadone treatment, thalassemic, dyalized included)
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
24442928
Citation
Santantonio T, Fasano M, Sagnelli E, Tundo P, Babudieri S, Fabris P, Toti M, Di Perri G, Marino N, Pizzigallo E, Angarano G; Acute Hepatitis C Study Group. Acute hepatitis C: a 24-week course of pegylated interferon alpha-2b versus a 12-week course of pegylated interferon alpha-2b alone or with ribavirin. Hepatology. 2014 Jun;59(6):2101-9. doi: 10.1002/hep.26991. Epub 2014 Apr 29.
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Evaluation of Peginterferon Alfa-2b Monotherapy and Combination With Ribavirin in Participants With Acute Hepatitis C (P03552/MK-4031-137)
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