Efficacy and Safety of Peginterferon Alfa-2b and Ribavirin Therapy in Subjects With Type C Compensated Liver Cirrhosis (Study P05116)

Treatment of Patients With Compensated Liver Cirrhosis With SCH 54031 + Ribavirin

The objective is to evaluate the efficacy and safety of combination therapy with peginterferon alfa-2b 1.0 µg/kg/week subcutaneous (SC) + ribavirin administered for 48 weeks in participants with chronic hepatitis C and type C compensated liver cirrhosis. Participants who are hepatitis C virus ribonucleic acid (HCV-RNA) positive after 24 weeks of treatment will be discontinued from therapy.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Hepatitis C, Chronic
• Intervention / Treatment: Biological: Peginterferon alfa-2b; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 20-70 years.
• Positive quantitative serum HCV-RNA.
• Participants classified as A in Child-Pugh classification, and who do not have ascites or hepatic encephalopathy.
• Diagnosed with type C compensated liver cirrhosis based on liver biopsy performed within 3 years or latest celioscopy.
• Prolonged prothrombin time by <=3.0 sec.
• Participants and partners of participants willing to use adequate contraception during the course of the study.
• Participants who can be hospitalized for at least 14 days since treatment initiation.
• Weight >40 kg and <=100 kg

• Hematology laboratory results of:

  • hemoglobin >=12 g/dL
  • neutrophil count >=1,500/mm^3
  • platelet count >=70,000/ mm^3

• Blood chemistry results of:

  • albumin and direct bilirubin within normal limits
  • alpha fetoprotein (AFP) within reference range
  • AFP-L3<=10%
  • Protein induced by vitamin K (PIVKA)-II <=100 mAU/mL

Exclusion Criteria:

• Participants who did not previously respond virologically to combination therapy with interferon (including polyethylene glycol-modified interferon) and ribavirin
• Participants who had previously received treatment with interferon for whom at least 90 days have not elapsed since the end of previous treatment
• Participants who have received treatment within 14 days prior to registration with injectable preparations containing glycyrrhizin/cysteine/glycyron or shosaikoto
• Participants who have received administration of drugs having antiviral, anti-tumor, or immuno-modulating effect (including glucocorticoids and radiation therapy) within 90 days prior to registration (excluding local administration and topicals)
• Participants who have received other investigational drugs within 180 days prior to registration
• Hepatitis B surface (HBs) antigen positive
• Antinuclear antibody >=320 times
• Serum creatinine exceeding the upper limit of reference range
• Participants with fasting blood glucose >=110 mg/dL (participants with fasting blood glucose >=110 mg/dL and <126 mg/dL can be registered if their hemoglobin A1C (HbA1c) is <6.5%) [fasting blood glucose should be measured when participants are not receiving treatment for diabetes mellitus]
• Participants with any of the following: diabetes mellitus that requires treatment; thyroid function disorder not controlled by treatment; liver disease such as autoimmune, alcoholic and drug-induced liver diseases; hemophilia; arrhythmia requiring treatment; co-existing hypertension not controlled by drug therapy (systolic blood pressure [BP] >=160mmHg or diastolic BP>=100mmHg); chronic pulmonary disease; hemoglobinopathies (thalassemia, sickle cell anemia); malignant tumors or who have a history of malignant tumor within the past 5 years; organ transplants (other than cornea and hair transplant)
• Participants with or who have a history of primary biliary cirrhosis, liver failure, hepatic carcinoma; decompensated liver cirrhosis with any the following diseases: ascites, jaundice, variceal hemorrhage, esophageal or gastric varices requiring treatment, hepatic encephalopathy, and idiopathic bacterial peritonitis; depression or schizophrenia requiring treatment, or suicidal attempt or suicidal ideation; epileptic seizures requiring treatment; angina, cardiac failure, myocardial infarction, or life-threatening arrhythmia; autoimmune disease (Hashimoto's disease, Crohn's disease, ulcerative colitis, chronic rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic erythematosus, autoimmune hemolytic anemia, scleroderma, etc.); hepatic carcinoma
• Participants with a history of hypersensitivity to interferon preparations, biological products such as vaccine, or nucleoside analogs, and those with specific reaction to pegylated interferon alfa-2b in the prick test conducted before the initiation of treatment
• Women who are pregnant or nursing as well as women for whom pregnancy cannot be ruled out by serum human chorionic gonadotropin (HCG) test conducted during the screening period. Male participants with partners who are pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Peginterferon alfa-2b + Ribavirin

Biological: Peginterferon alfa-2b; Administered at 1.0 µg/kg/week SC for 48 weeks; Other Names: SCH 054031; Drug: Ribavirin; Administered based on body weight and hemoglobin value at Screening: 600-1000 mg/day for subjects with hemoglobin value at screening >=14g/dL, and 400-800 mg/day for subjects with hemoglobin value at screening >=12g/dL and <14g/dL; treatment duration is 48 weeks; Other Names: SCH 018908

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Undetectable HCV-RNA at Week 72 (Sustained Virologic Response)	Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR)	Measured at 24 weeks after 48 weeks treatment (72 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Undetectable HCV-RNA at Week 24	Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR)	Week 24
Number of Participants With Undetectable HCV-RNA at End of Treatment	Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR)	Up to 48 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: May 27, 2008
• First Submitted That Met QC Criteria: May 29, 2008
• First Posted (Estimate): May 30, 2008

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: hepatitis C
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Fibrosis; Hepatitis; Hepatitis C; Liver Cirrhosis; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2b
• Other Study ID Numbers: P05116; JPC-06-320-35

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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