Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Combination Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) in Genotype 2 Hepatitis C Infection (MK-5172-047)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01932762
Recruitment Status : Completed
First Posted : August 30, 2013
Results First Posted : March 4, 2016
Last Update Posted : February 4, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE August 27, 2013
First Posted Date  ICMJE August 30, 2013
Results First Submitted Date  ICMJE February 3, 2016
Results First Posted Date  ICMJE March 4, 2016
Last Update Posted Date February 4, 2021
Actual Study Start Date  ICMJE October 1, 2013
Actual Primary Completion Date December 4, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • Percentage of Participants With Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12) [ Time Frame: 12 weeks after end of all therapy (Study Week 24) ]
    SVR12 was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) <25 IU/mL, either target detected but unquantifiable (TD[u]) or target not detected (TND), at 12 weeks after the end of all study therapy. The percentage of participants with SVR12 and accompanying 95% confidence intervals (CIs) were reported for each treatment arm in the Per-Protocol (PP) Population.
  • Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Drug-Related AEs, Drug-Related SAEs, or Discontinuation of Study Treatment Due to AE During the Treatment Period and First 14 Follow-up Days [ Time Frame: Treatment period plus the first 14 days of follow-up (up to 14 weeks) ]
    AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The investigator determined the relationship of the AE to the treatment as unrelated or possibly, probably, or definitely related.
Original Primary Outcome Measures  ICMJE
 (submitted: August 27, 2013)
  • Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12) [ Time Frame: From Treatment Week (TW) 1 to Follow-up Week (FW) 12 (up to 24 weeks) ]
  • Percentage of Participants with Adverse Events (AEs), Serious AEs (SAEs), Drug-Related AE, Drug-Related SAE, or Discontinuation Due to AE [ Time Frame: From TW1 through FW 24 (up to 36 weeks) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • Mean Time to First Achievement of Undetectable HCV RNA During Treatment [ Time Frame: From TW1 until first achievement of undetectable HCV RNA (up to 12 weeks) ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. Undetectable HCV RNA (or TND) was defined as below the 9.3 IU/ml limit of detection. Kaplan Meier summary statistics were calculated for each treatment arm in the Full Analysis Set (FAS).
  • Percentage of Participants Achieving Undetectable HCV RNA During Treatment By Timepoint [ Time Frame: From TW 2 through TW 12 (up to 12 weeks) ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. Undetectable HCV RNA (or TND) was defined as below the 9.3 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2, TW4, and TW12 for each treatment arm of the PP Population.
  • Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment By Timepoint [ Time Frame: From TW 2 through TW 12 (up to 12 weeks) ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. The Roche COBAS™ Taqman™ HCV Test (v.2.0) has a lower limit of quantification (LLoQ) of 25 IU/ml and a limit of detection of 9.3 IU/ml. The percentage of participants with HCV RNA levels <25 IU/ml (either TD[u] or TND) and accompanying 95% CIs were reported at TW2, TW4, and TW12 for each treatment arm of the PP Population.
  • Percentage of Participants Achieving SVR4 [ Time Frame: 4 weeks after end of all therapy (Study Week 16) ]
    SVR4 was defined as HCV RNA <25 IU/mL, either TD(u) or TND, at 4 weeks after the end of all study therapy. The percentage of participants with SVR4 and accompanying 95% CIs were reported for each treatment arm of the PP Population.
  • Percentage of Participants Achieving SVR24 [ Time Frame: 24 weeks after end of all therapy (Study Week 36) ]
    SVR24 was defined as HCV RNA <25 IU/mL, either TD(u) or TND, at 24 weeks after the end of all study therapy. The percentage of participants with SVR24 and accompanying 95% CIs were reported for each treatment arm of the PP Population.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2013)
  • Time to First Achievement of Undetectable HCV RNA [ Time Frame: From TW1 through FW 24 (up to 36 weeks) ]
  • Percentage of Participants Achieving Undetectable HCV RNA [ Time Frame: From TW 1 through TW 12 (up to 12 weeks) ]
  • Percentage of Participants Achieving HCV RNA <25 IU/mL [ Time Frame: From TW 1 through TW 12 (up to 12 weeks) ]
  • Percentage of Participants Achieving SVR4 [ Time Frame: From TW1 through FW 4 (up to 16 weeks) ]
  • Percentage of Participants Achieving SVR24 [ Time Frame: From TW1 through FW 24 (up to 36 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Combination Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) in Genotype 2 Hepatitis C Infection (MK-5172-047)
Official Title  ICMJE A Phase II Clinical Trial to Evaluate the Efficacy and Safety of a Combination Regimen of MK-5172 With/Without MK-8742 and/or Ribavirin (RBV) in Treatment-naive Subjects With Chronic Hepatitis C Genotype 2, 4, 5 and 6 Infection
Brief Summary

This is a multi-site, open-label trial evaluating the safety and efficacy of 100 mg of grazoprevir (MK-5172) used in combination with or without 50 mg of elbasvir (MK-8742) and/or ribavirin (RBV) in treating non-cirrhotic treatment-naïve participants with chronic genotype (GT) 2, 4, 5, and 6 hepatitis C infection.

In Part A there is no randomization or stratification; all GT2 participants will be assigned to arm A1. In Part B, all GT2 participants will be assigned to Arm B1 and all participants with GT4, GT5 and GT6 will be randomized in a 1:1 ratio to either Arm 3 or Arm 4 with stratification by genotype.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE
  • Drug: Grazoprevir
    100 mg every day (QD) orally
    Other Name: MK-5172
  • Drug: Elbasvir
    50 mg QD orally
    Other Name: MK-8742
  • Drug: Ribavirin
    Administered twice daily (BID) orally at a total daily dose of 800 mg to 1400 mg based on participant's weight on Day 1
    Other Name: Rebetol™
Study Arms  ICMJE
  • Experimental: GT2: Grazoprevir + Elbasvir + RBV (Arm A1)
    During Part A of the study, GT2 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
    • Drug: Ribavirin
  • Experimental: GT2: Grazoprevir + RBV (Arm B1)
    During Part B of the study, GT2 participants will receive 100 mg grazoprevir + standard weight-based dosing of RBV for 12 weeks.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Ribavirin
  • Experimental: GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)
    During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
    • Drug: Ribavirin
  • Experimental: GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
    During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir for 12 weeks.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 17, 2014)
98
Original Estimated Enrollment  ICMJE
 (submitted: August 27, 2013)
30
Actual Study Completion Date  ICMJE December 4, 2014
Actual Primary Completion Date December 4, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Parts A and B: -Body weight ≥50 kg (111 lbs) and ≤ 125 kg (275 lbs) -Has absence of cirrhosis -Agrees to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female participant who is of childbearing potential or male participant with female sexual partner who is of childbearing potential).

Part A only: -Has chronic HCV GT2 infection Part B only: -Has chronic HCV GT2, GT4, GT5, or GT6 infection

Exclusion Criteria:

Parts A and B:

-Is not treatment naïve (participant has had previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV) -Is determined to be coinfected with hepatitis B virus (HBsAg positive) or HIV -Has evidence of, or is under evaluation for, hepatocellular carcinoma (HCC) -Has a clinical diagnosis of substance abuse including the following specified drugs within specified timeframes: Alcohol, intravenous drugs, inhalational, psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs (within 1 year of the screening visit), is receiving opiate agonist substitution therapy (within 1 year of screening visit), or excessive historic marijuana use -Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years -Female participant who is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment, or male participant who is planning to impregnate or provide sperm donation or has a female sexual partner of childbearing potential and is unwilling to commit to using a two methods of birth control throughout treatment and after the completion of all treatment -Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis. -Has uncontrolled diabetes (documented HbA1c >8.5%)

Part A only:

-Has non GT2 HCV infection

Part B only:

-Has HCV infection with a genotype other than GT2, GT4, GT5 or GT6

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Belgium,   France,   Israel,   Spain,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT01932762
Other Study ID Numbers  ICMJE 5172-047
2013-002169-21 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP