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Trial record 40 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Study of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Japanese Participants With Chronic Hepatitis C (MK-5172-058)

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: NCT02203149
Recruitment Status : Completed
First Posted : July 29, 2014
Results First Posted : October 11, 2016
Last Update Posted : September 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE July 25, 2014
First Posted Date  ICMJE July 29, 2014
Results First Submitted Date  ICMJE August 18, 2016
Results First Posted Date  ICMJE October 11, 2016
Last Update Posted Date September 24, 2018
Actual Study Start Date  ICMJE August 1, 2014
Actual Primary Completion Date October 2, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
  • Part 2: Percentage of Treatment-naïve Participants in the Immediate Treatment Arm Achieving Sustained Viral Response at 12 Weeks After The End of All Treatment (SVR12) [ Time Frame: 12 weeks after end of all therapy in Part 2 (Study Week 24 of Part 2) ]
    Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® Taqman quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, v2.0, which had a lower limit of quantification (LLoQ) of 1.2 Log IU/mL (15 IU/mL) and a lower limit of detection (LLoD) below 15 IU/ml (no specific value). SVR12 was defined as undetectable HCV RNA (target not detected) at 12 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals (CIs) for the SVR12 rate. The lower limit of the 95% CI was compared to the reference rate of 75%; a lower CI limit that was higher than the reference rate would confirm the primary hypothesis and indicate that that the treatment combination was efficacious. As pre-specified in the protocol, only the Immediate Treatment Arm of Part 2 (treatment naïve participants) was included in the primary efficacy analysis.
  • Part 1: Percentage of Participants Experiencing an Adverse Event (AE) During Treatment and First 4 Follow-Up Weeks [ Time Frame: Up to 4 weeks post last dose in Part 1 (Up to total of 16 weeks) ]
    An 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 unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through Follow-up Week 4 (FUWK4).
  • Part 1: Percentage of Participants That Discontinued Treatment Due to an AE [ Time Frame: Up to Study Week 12 in Part 1 ]
    An 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 unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through FUWK4.
  • Part 2: Percentage of Participants Experiencing an AE During Initial Treatment and First 4 Follow-Up Weeks [ Time Frame: Up to 4 weeks following initial treatment in Part 2 (Up to total of 16 weeks) ]
    An 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 unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
  • Part 2: Percentage of Participants That Discontinued Initial Treatment Due to an AE [ Time Frame: Up to Study Week 12 in Part 2 ]
    An 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 unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
Original Primary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
Proportion of Participants Achieving SVR12 [ Time Frame: Up to Week 40 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
  • Part 1: Percentage of Participants Achieving Undetectable HCV RNA Over Time [ Time Frame: Part 1 Treatment Weeks (TW)2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 ]
    Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
  • Part 1: Percentage of Participants Achieving HCV RNA Below the Lower Limit of Quantitation (<LLoQ) Over Time [ Time Frame: Part 1 TW2, TW4, TW12, EOT, FUWK4, FUWK12, FUWK24 ]
    Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA <LLoQ at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
  • Part 2: Percentage of Participants Achieving Undetectable HCV RNA Over Time After Active Treatment [ Time Frame: Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 ]
    Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
  • Part 2: Percentage of Participants Achieving HCV RNA <LLoQ Over Time After Active Treatment [ Time Frame: Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 ]
    Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA <LLoQ at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
  • Number of Participants Experiencing an Adverse Events (AE) [ Time Frame: Up to Week 52 ]
  • Number of Participants Withdrawing from Study Therapy due to AEs [ Time Frame: Up to Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Japanese Participants With Chronic Hepatitis C (MK-5172-058)
Official Title  ICMJE A Phase II, Randomized Clinical Trial to Study the Safety, Tolerability, and Efficacy of the Combination Regimen of MK-5172 and MK-8742 in Japanese Subjects With Chronic Hepatitis C and a Phase III, Randomized Placebo-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of the Combination Regimen of MK-5172 and MK-8742 in Japanese Subjects With Chronic Hepatitis C
Brief Summary This is a two-part study of grazoprevir (MK-5172) + elbasvir (MK-8742) in Japanese participants with chronic hepatitis C virus (HCV) genotype 1 (GT1). Part I is a dose-finding study; in Part II, participants will be randomly assigned to receive grazoprevir at the dose determined in Part I in combination with elbasvir. The primary study hypothesis is that the percentage of treatment-naïve participants in the Immediate Treatment Arm of Part II who achieve sustained viral response at 12 weeks after the end of all treatment (SVR12) will be greater than the reference rate of 75%. A separate study arm for cirrhotic participants will also be included in Part II; these participants will receive grazoprevir at the determined dose in combination with elbasvir.
Detailed Description

In Part 1, HCV GT1 participants are randomized into one of two arms: 50 mg grazoprevir plus 50 mg elbasvir for 12 weeks during the double blinded (DB) period followed by 24 weeks of follow-up (FU) during an open-label (OL) period [Arm 1]; or 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks during the DB followed by 24 weeks of FU during the OL [Arm 2]. Unblinding will occur after all participants complete FU Week 4 at which time the grazoprevir dose will be selected.

In Part 2, non-cirrhotic HCV GT1 participants and GT1 participants with compensated liver cirrhosis all receive the selected dose of grazoprevir (50 mg or 100 mg from Part 1) with 50 mg elbasvir for 12 weeks. Non-cirrhotic GT1 participants are randomized to receive either a) 12 weeks of active treatment immediately during the DB with 24 weeks of FU in the OL [Arm 1/Immediate Arm] or b) placebo for 12 weeks with 4 weeks of follow-up during the DB followed by 12 weeks of active treatment and 24 weeks of follow-up during the OL [Arm 2/Deferred Arm]. All cirrhotic participants [Arm 3/Cirrhotic] receive the selected dose immediately for 12 weeks during the DB with 24 weeks of FU during the OL.

Safety analyses for Part 1 and Part 2 arms will focus on the 12 week treatment phase plus the first 4 FU weeks. For the Part 2 Deferred Arm this will include the initial 12 week placebo treatment and first 4 weeks of FU. Efficacy analyses for Parts 1 and 2 will evaluate active treatment only (Weeks 1-12 for all arms except for Part 2 Deferred Arm which is weeks 16-28).

Part 1:

50 mg grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 1) 100 mg grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2)

Part 2:

Selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 1/Immediate) Placebo treatment for 12 weeks, 4 weeks follow-up, selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2/Deferred) Selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 3/Cirrhotic)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE
  • Drug: Grazoprevir
    One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks.
  • Drug: Elbasvir
    One 50 mg tablet taken orally once daily for 12 weeks.
  • Drug: Placebo to Grazoprevir
    One tablet of placebo matched to grazoprevir, taken orally once daily for 12 weeks.
  • Drug: Placebo to Elbasvir
    One tablet of placebo matched to elbasvir, taken orally once daily for 12 weeks.
Study Arms  ICMJE
  • Experimental: Part 1 Grazoprevir 50 mg + Elbasvir
    Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir by mouth (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
    • Drug: Placebo to Grazoprevir
  • Experimental: Part 1 Grazoprevir 100 mg + Elbasvir
    Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
  • Experimental: Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir
    Non-cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2 and are followed-up for 24 weeks during the open-label period of Part 2.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
  • Placebo Comparator: Part 2 Non-cirrhotic Deferred: Placebo► Grazoprevir + Elbasvir
    Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
    • Drug: Placebo to Grazoprevir
    • Drug: Placebo to Elbasvir
  • Experimental: Part 2 Cirrhotic: Grazoprevir + Elbasvir
    Cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part 1) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
    Interventions:
    • Drug: Grazoprevir
    • Drug: Elbasvir
Publications * Kumada H, Suzuki Y, Karino Y, Chayama K, Kawada N, Okanoue T, Itoh Y, Mochida S, Toyoda H, Yoshiji H, Takaki S, Yatsuzuka N, Yodoya E, Iwasa T, Fujimoto G, Robertson MN, Black S, Caro L, Wahl J. The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study. J Gastroenterol. 2017 Apr;52(4):520-533. doi: 10.1007/s00535-016-1285-y. Epub 2016 Nov 21.

*   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: May 7, 2015)
399
Original Estimated Enrollment  ICMJE
 (submitted: July 25, 2014)
330
Actual Study Completion Date  ICMJE May 16, 2016
Actual Primary Completion Date October 2, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has documented chronic Japanese HCV genotype (GT) 1 with no evidence of non-typeable or mixed GT infection
  • Is treatment-naïve, or intolerant or non-responder to prior anti-HCV interferon (IFN)-based treatment without direct acting antiviral (DAA) therapy, prior IFN-based treatment with DAA therapy, or prior DAA therapy
  • Agrees to the use of contraception if a female of reproductive potential

Exclusion Criteria:

  • Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease
  • Is coinfected with hepatitis B virus or human immunodeficiency virus (HIV)
  • Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ
  • Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC (Part 2 only)
  • Has clinically-relevant drug or alcohol abuse within 12 months of screening
  • Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 and continue throughout treatment and follow-up (or longer if dictated by local regulations)
  • Has any of the following conditions:
  • Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
  • Poor venous access
  • History of gastric surgery (e.g., stapling, bypass) or subject with a history of malabsorption disorders (e.g., celiac sprue disease)
  • History of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures
  • Medical/surgical conditions that may result in a need for hospitalization during the period of the study
  • Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, TNF antagonists, or other immunosuppressant drugs during the course of the trial
  • Has chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 80 Years   (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 Japan
 
Administrative Information
NCT Number  ICMJE NCT02203149
Other Study ID Numbers  ICMJE 5172-058
142638 ( Registry Identifier: JAPIC-CTI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/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 August 2018

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