A Pharmacokinetics/Pharmacodynamics Study of SCH 900518 in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C (Protocol No. P05104AM2)(COMPLETED)

NCT00797745 | Completed Phase 2 DMC

• 1 other identifier: P05104
• Study Type: interventional
• Target: 111
• Locations: 0 countries
• Sites: N/A

Brief Summary

SCH 900518 is a potent oral inhibitor of HCV NS3 protease which disrupts hepatitis C virus (HCV) polyprotein processing. SCH 900518, when added to the current standard of care (SOC), peginterferon-alfa plus ribavirin, would likely increase the proportion of patients achieving undetectable HCV-RNA levels and sustained virologic response (SVR). In this study, SCH 900518 would be used in combination with low doses of ritonavir to enhance the levels of SCH 900518 within the body and reduce the number of daily SCH 900518 tablets required. The purpose of this study is to identify the optimal dose and schedule (once or twice a day) of SCH 900518 plus ritonavir in previously untreated patients with genotype 1 chronic hepatitis C when given in combination with SOC. The study compares SOC to 6 experimental arms. In the experimental arms, SOC plus SCH 900518 doses of 200, 400 and 600 mg once daily or 100 mg twice daily with ritonavir 100 mg once or twice daily will be explored. The benefits of a 4 week lead-in with PegIntron and ribavirin prior to the addition of SCH 900518 will also be explored.

Conditions

Hepatitis C, Chronic

Keywords

genotype 1 infection

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint is the proportion of subjects with undetectable HCV-RNA after 4 weeks of treatment with SCH 900518.

  After 4 weeks of treatment with SCH 900518

Secondary Outcomes (3)

• Rate of viral decline during the first 4 weeks of dosing with SCH 900518

  After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24

• Proportion of subjects with undetectable HCV-RNA at both 4 and 12 weeks of dosing with SCH 900518

  After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24

• Proportion of subjects with undetectable HCV-RNA at end of treatment (EOT) and follow-up week 24 (FW24)

  After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24

Study Arms (7)

Standard of Care

ACTIVE COMPARATOR

PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily for 48 weeks. * Subjects with \>= 1 log decrease from baseline in HCV-RNA levels after 12 weeks, but still above the lower limit of quantitation, have the option of crossing over to PegIntron, ribavirin plus SCH 900518 400 mg and ritonavir 100 mg daily for 12 weeks. This is followed by standard of care, PegIntron and ribavirin, for a total treatment duration of up to 48 weeks.

Biological: peginterferon alfa 2b; Drug: ribavirin; Drug: SCH 900518; Drug: ritonavir

2

EXPERIMENTAL

PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 200 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.

Biological: peginterferon alfa 2b; Drug: ribavirin; Drug: SCH 900518; Drug: ritonavir

3

EXPERIMENTAL

PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 400 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.

Biological: peginterferon alfa 2b; Drug: ribavirin; Drug: SCH 900518; Drug: ritonavir

4

EXPERIMENTAL

4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 200 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.

Biological: peginterferon alfa 2b; Drug: ribavirin; Drug: SCH 900518; Drug: ritonavir

5

EXPERIMENTAL

4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 400 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.

Biological: peginterferon alfa 2b; Drug: ribavirin; Drug: SCH 900518; Drug: ritonavir

6

EXPERIMENTAL

PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 100 mg twice daily plus ritonavir 100 mg twice daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.

Biological: peginterferon alfa 2b; Drug: ribavirin; Drug: SCH 900518; Drug: ritonavir

7

EXPERIMENTAL

4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 600 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.

Biological: peginterferon alfa 2b; Drug: ribavirin; Drug: SCH 900518; Drug: ritonavir

Interventions

peginterferon alfa 2b BIOLOGICAL

1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks

Also known as: PegIntron

2; 3; 4; 5; 6; 7; Standard of Care

ribavirin DRUG

ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks

Also known as: REBETOL

2; 3; 4; 5; 6; 7; Standard of Care

SCH 900518 DRUG

SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.

2; 3; 4; 5; 6; 7; Standard of Care

ritonavir DRUG

Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.

Also known as: Norvir

2; 3; 4; 5; 6; 7; Standard of Care

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult subjects with CHC HCV genotype 1 with no previous treatment for CHC
• to 55 years of age
• Weight between 40 and 125 kg
• Previously documented CHC genotype 1 infection
• Liver biopsy within 2 years of Screening with histology consistent with chronic hepatitis C and no evidence of bridging fibrosis or cirrhosis
• Subject and subject'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
• Subjects must be willing to give written informed consent

You may not qualify if:

• Prior treatment for hepatitis C other than herbal remedies
• HIV positive or known to be co-infected with hepatitis B
• Medically significant gallbladder or hepatobiliary findings on Screening ultrasound
• Use of any known significant inducers or substrates of CYP3A4 two weeks prior to start of study medications
• Use of herbal supplements (Milk Thistle permitted)
• Diabetic and hypertensive subjects with clinically significant ocular examination findings
• Current moderate or severe depression
• History of depression associated with any of the following:
• Hospitalization for depression
• Electroconvulsive therapy for depression.
• Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions
• Suicidal or homicidal ideation and/or attempt
• History of severe psychiatric disorders
• Past history or current use of lithium
• Clinical diagnosis of substance abuse of alcohol, intravenous drugs, inhalational (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs within 5 years of Day 1

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2b; Ribavirin; narlaprevir; Ritonavir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2008
• First Posted: November 25, 2008
• Study Start: November 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: September 1, 2010
• Last Updated: January 22, 2015

Record last verified: 2015-01