Safety and Efficacy of Vaniprevir (MK-7009) With Pegylated Interferon (Peg-IFN) and Ribavirin (RBV) in Treatment-Experienced Hepatitis C Virus (HCV) Participants (MK-7009-009)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00704405
First received: June 23, 2008
Last updated: September 26, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to test the safety, tolerability, and efficacy of 4 regimens of Vaniprevir + Peg-IFN and Ribavirin as compared to Placebo (PBO) + Peg-IFN/RBV. The primary hypotheses are that Vaniprevir is well tolerated, and that Vaniprevir 600 mg twice daily (b.i.d.) is superior to the control regimen for the percentage of non-cirrhotic (NC) participants achieving undetectable HCV ribonucleic acid (RNA) 24 weeks after the end of study therapy (SVR24).


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Vaniprevir
Drug: Pegylated Interferon (Peg-IFN)
Drug: Ribavirin (RBV)
Drug: Placebo (PBO)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of 4 Different Regimens of MK-7009 When Administered Concomitantly With Pegylated Interferon and Ribavirin in Treatment-Experienced Patients With Chronic Genotype 1 Hepatitis C Virus Infection

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 600 mg b.i.d. [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: No ]
    The percentage of non-cirrhotic participants with undetectable Hepatits C virus (HCV) ribonucleic acid (RNA) 24 weeks after completing treatment was determined for each Vaniprevir 600 mg b.i.d. and control regimen. Results for Vaniprevir 300 mg are presented as a Secondary Outcome Measure.

  • Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to 73 weeks ] [ Designated as safety issue: Yes ]
    The number of non-cirrhotic participants experiencing AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen. An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product.

  • Number of Participants Discontinuing From Study Treatment Due to AEs [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: Yes ]
    The number of non-cirrhotic participants withdrawing from study treatment due to AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen.


Secondary Outcome Measures:
  • Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 300 mg b.i.d. [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
    The percentage of non-cirrhotic participants treated with Vaniprevir 300 mg b.i.d. with undetectable HCV RNA 24 weeks after completing treatment was determined.

  • Percentage of Participants Achieving cEVR [ Time Frame: Up to Week 60 ] [ Designated as safety issue: No ]
    The percentage of non-cirrhotic participants with complete early viral response (cEVR; undetectable HCV RNA at Week 12) was determined for each Vaniprevir dose. Since each of the Vaniprevir 600 mg arms had the same treatment history at this point in the study, the data were pooled for analysis.

  • Percentage of Participants Achieving SVR24 After 24 Weeks of Vaniprevir 600 mg b.i.d. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants achieving SVR24 after the 24-week Vaniprevir 600 mg b.i.d. regimen at Week 48 was compared to the control regimen.


Enrollment: 285
Study Start Date: March 2009
Study Completion Date: September 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 24-wk Vaniprevir 600 mg + Peg-IFN/RBV
Vaniprevir 600 mg (total daily dose) and RBV (1000 mg or 1200 mg total daily dose based on body weight) twice daily (b.i.d.) and Peg-IFN 180 mcg injection once weekly for 24 weeks.
Drug: Vaniprevir
Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.
Other Name: MK-7009
Drug: Pegylated Interferon (Peg-IFN)
Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks
Other Name: PEGASYS™
Drug: Ribavirin (RBV)
Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.
Other Name: COPEGUS™
Experimental: 24-wk Vaniprevir 600 mg + 24-wk PBO + Peg-IFN/RBV
Vaniprevir 600 mg (total daily dose) and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 24 weeks, followed by PBO and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for an additional 24 weeks.
Drug: Vaniprevir
Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.
Other Name: MK-7009
Drug: Pegylated Interferon (Peg-IFN)
Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks
Other Name: PEGASYS™
Drug: Ribavirin (RBV)
Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.
Other Name: COPEGUS™
Drug: Placebo (PBO)
Participants took PBO capsules matching Vaniprevir capsules, three in the morning and three in the evening, for 24 or 48 weeks.
Experimental: 48-wk Vaniprevir 300 mg + Peg-IFN/RBV
Vaniprevir 300 mg (total daily dose, taken once daily [q.d.]) and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks.
Drug: Vaniprevir
Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.
Other Name: MK-7009
Drug: Pegylated Interferon (Peg-IFN)
Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks
Other Name: PEGASYS™
Drug: Ribavirin (RBV)
Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.
Other Name: COPEGUS™
Experimental: 48-wk Vaniprevir 600 mg + Peg-IFN/RBV
Vaniprevir 600 mg and RBV (1000 mg or 1200 mg based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks.
Drug: Vaniprevir
Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.
Other Name: MK-7009
Drug: Pegylated Interferon (Peg-IFN)
Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks
Other Name: PEGASYS™
Drug: Ribavirin (RBV)
Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.
Other Name: COPEGUS™
Placebo Comparator: 48-wk PBO + Peg-IFN/RBV
PBO and RBV (1000 mg or 1200 mg based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks.
Drug: Pegylated Interferon (Peg-IFN)
Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks
Other Name: PEGASYS™
Drug: Ribavirin (RBV)
Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.
Other Name: COPEGUS™
Drug: Placebo (PBO)
Participants took PBO capsules matching Vaniprevir capsules, three in the morning and three in the evening, for 24 or 48 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Has chronic HCV genotype 1 infection
  • Is treatment-experienced
  • For the non-cirrhotic population, has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma; for the cirrhotic population, has had a liver biopsy with evidence of cirrhosis and without evidence of hepatocellular carcinoma.

Exclusion criteria:

  • Has not tolerated previous course peg-IFN and RBV
  • Is unlikely to tolerate at least 24 weeks of continuous therapy with Peg-IFN and RBV
  • Is co-infected with Human Immunodeficiency Virus (HIV) and/or hepatitis B
  • Consumes excessive amounts of alcohol
  • Has a history of drug or alcohol abuse
  • If female, participant is pregnant or breastfeeding
  • Has been in a clinical trail with an investigational drug in the last 30 days
  • Has used IFN/Peg-IFN and RBV in the last 3 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704405

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00704405     History of Changes
Other Study ID Numbers: 7009-009, 2007_659
Study First Received: June 23, 2008
Results First Received: September 26, 2014
Last Updated: September 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Interferons
Ribavirin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2014