Effect of Insulin Resistance on the Safety and Efficacy of Pegylated Interferon and Ribavirin Treatment in HCV (Study P05562)

• ClinicalTrials.gov Identifier: NCT00705224
• Recruitment Status: Completed
• First Posted: June 25, 2008
• Results First Posted: September 16, 2011
• Last Update Posted: July 1, 2015
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

Naïve patients with chronic hepatitis C (CHC) of any genotype will be treated with a standard treatment regimen (pegylated interferon and ribavirin) according to routine clinical practice in Russia. The objective of this study is to examine the influence of insulin resistance on the safety and efficacy of treatment with pegylated interferon and ribavirin and to determine the prevalence of insulin resistance in different populations of CHC patients.

Condition or disease	Intervention/treatment
Hepatitis C, Chronic; Hepatitis C Virus	Biological: Pegylated Interferon; Drug: Ribavirin

Detailed Description:

consecutive patient sampling

Study Design

• Study Type: Observational
• Actual Enrollment: 250 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Observational Multicenter Study to Evaluate Influence of Insulin Resistance on the Safety and Efficacy (as Measured by Sustained Virological Response) of Treatment With Any Pegylated Interferon and Ribavirin (Standard of Care) in Different Populations of HCV Patients in Russia.
• Study Start Date: May 2008
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: August 2010

Groups and Cohorts

Group/Cohort

Intervention/treatment

Patients with chronic hepatitis C; Naïve patients with chronic hepatitis C (CHC) of any genotype will be treated with a standard treatment regimen (pegylated interferon and ribavirin) according to routine clinical practice in Russia.

Biological: Pegylated Interferon; Routine treatment with a combination of any pegylated interferon and ribavirin was used according to the label/local practice in Russia. The treatment course duration complied with the labeled dosage regimen. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype, viral load, activity and stage of hepatitis C. The Sponsor did not provide formal drug supply.; Other Names: PegIntron; (SCH 54031); Drug: Ribavirin; Routine treatment with a combination of any pegylated interferon and ribavirin was used according to the label/local practice in Russia. The treatment course duration complied with the labeled dosage regimen. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C. The Sponsor did not provide formal drug supply.; Other Names: Rebetol; (SCH 18908)

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study [ Time Frame: 24 weeks following completion of 24 or 48 weeks of therapy ]
   Sustained Virological response (SVR) was assessed at the end of the study (Visit 4) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively.

Secondary Outcome Measures :

1. Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline [ Time Frame: 24 weeks following completion of 24 or 48 weeks of therapy ]
   SVR was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as Homeostasis model assessment - of insulin-resistance [HOMA-IR] >3) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively.
2. Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline [ Time Frame: Week 24 or 48 after treatment start ]
   Response following treatment (RFT) was assessed at the end of treatment (Visit 3) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the presence or absence of RFT. RFT was defined as undetectable plasma HCV-RNA at end of treatment. Visit 3 was considered Week 24 or Week 48 after treatment start depending on treatment duration.
3. Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline [ Time Frame: 24 weeks following completion of 24 or 48 weeks of therapy ]
   Virological relapse (VR) was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the percentage of participants who demonstrated VR. VR was defined as undetectable plasma HCV-RNA (RFT +) at end of treatment (Visit 3- considered Week 24 or Week 48 after treatment start depending on treatment duration), but lost RFT (considered sustained non-Responders) at end of study (Visit 4- considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively).
4. Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline [ Time Frame: Week 12 after treatment start ]
   Early Virological response (EVR) was assessed at 12 weeks after treatment start (Visit 2) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the percentage of participants who achieved EVR. EVR was defined as a substantial (greater than 2 log10) decrease in viral load (measured as International Units/milliliter) and/or negative Polymerase chain reaction (PCR)-based viral load qualitative result as assessed at visit 2 of the study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

The study will include naïve patients with chronic hepatitis C (CHC) of any genotype who will be treated with a standard treatment regimen (pegylated interferon and ribavirin) according to routine clinical practice in Russia.

Criteria

Inclusion Criteria:

• Confirmed diagnosis of CHC according to local regulations
• Naïve Pegylated Interferon (PEG-IFN) CHC patient
• No contraindications for PEG-IFN CHC therapy
• Negative urine pregnancy test result (for females of childbearing potential) documented within the 24-hour period prior to the first dose of study drugs. Additionally, all female patients of childbearing potential and all males with female partners of childbearing potential must use two forms of effective contraception (combined) during treatment and 6 months after treatment end
• Willingness to give written informed consent and willingness to participate in and comply with the study requirements.

Exclusion Criteria:

• PEG-IFN treatment in history
• Contraindications for PEG-IFN CHC therapy
• Females who are pregnant or breast-feeding
• Male partners of females who are pregnant
• Potentially unreliable participants, and those judged by the investigator to be unsuitable for the study.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00705224
• Other Study ID Numbers: P05562
• First Posted: June 25, 2008
• Results First Posted: September 16, 2011
• Last Update Posted: July 1, 2015
• Last Verified: June 2015

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Insulin Resistance; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Hepatitis, Chronic; Interferons; Ribavirin; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action