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Efficacy and Safety of Uprifosbuvir (MK-3682) + Ruzasvir (MK-8408) in Treating Hepatitis C Virus Infection Genotypes 1-6 (MK-3682-041)

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ClinicalTrials.gov Identifier: NCT02956629
Recruitment Status : Terminated (The study was terminated based on review of Phase 2 efficacy data)
First Posted : November 6, 2016
Results First Posted : December 26, 2018
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE November 2, 2016
First Posted Date  ICMJE November 6, 2016
Results First Submitted Date  ICMJE December 3, 2018
Results First Posted Date  ICMJE December 26, 2018
Last Update Posted Date June 25, 2019
Actual Study Start Date  ICMJE November 16, 2016
Actual Primary Completion Date December 22, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2018)
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Completing Study Therapy (SVR12) [ Time Frame: 12 weeks after completing study therapy (Week 24) ]
    Plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA) were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from participants. SVR12 is the absence of detectable RNA of the hepatitis C virus, (<lower limit of quantification [LLOQ] of 15 IU/mL) for at least 12 weeks after completing treatment.
  • Percentage of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to Week 14 ]
    An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example ), 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 infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
  • Percentage of Participants Experiencing an AE of Clinical Importance (ECI) [ Time Frame: Up to Week 14 ]
    Adverse events of clinical importance, excluding overdoses include, but is not limited to, significant changes in alanine aminotransferase, aspartate aminotransferase, blood creatinine, glomerular filtration rate or hepatitis B reactivation.
  • Percentage of Participants Experiencing a Serious Adverse Event (SAE) [ Time Frame: Up to Week 14 ]
    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is an other important medical event; is a cancer; is associated with an overdose.
  • Percentage of Participants Experiencing a Drug-related AE [ Time Frame: Up to Week 14 ]
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example ), 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 infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE is determined by the investigator to be related to the use of the drug.
  • Percentage of Participants Experiencing a Drug-related SAE [ Time Frame: Up to Week 14 ]
    A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is an other important medical event; is a cancer; is associated with an overdose. A drug-related SAE is determined by the investigator to be related to the use of the drug.
  • Percentage of Participants Discontinuing Study Therapy Due to an AE [ Time Frame: Up to Week 12 ]
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example ), 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 infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Original Primary Outcome Measures  ICMJE
 (submitted: November 3, 2016)
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Completing Study Therapy (SVR12) [ Time Frame: 12 weeks after completing study therapy (Week 24) ]
  • Percentage of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to Week 14 ]
  • Percentage of participants experiencing an AE of clinical importance [ Time Frame: Up to Week 14 ]
  • Percentage of participants experiencing a severe adverse event (SAE) [ Time Frame: Up to Week 14 ]
  • Percentage of Participants Experiencing a Drug-related AE [ Time Frame: Up to Week 14 ]
  • Percentage of Participants Experiencing a Drug-related SAE [ Time Frame: Up to Week 14 ]
  • Percentage of Participants Discontinuing Study Therapy Due to an AE [ Time Frame: Up to Week 12 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2018)
  • Percentage of Participants With SVR 24 Weeks After Completing Study Therapy (SVR24) [ Time Frame: 24 weeks after completing study therapy (Week 36) ]
    Plasma levels of HCV RNA) were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from participants. SVR24 is the absence of detectable RNA of the hepatitis C virus (<LLOQ of 15 IU/mL), for at least 24 weeks after completing treatment.
  • Percentage of Participants With Virologic Failure [ Time Frame: Up to Week 24 ]
    Virologic failure is the detection of HCV RNA among participants who do not discontinue study for non-treatment-related reasons, either due to on-treatment failure defined as either non-response where HCV RNA is detected at end of treatment without HCV RNA <LLOQ having been achieved while on treatment; rebound defined as >1 log10 IU/mL increase in HCV RNA from nadir while on treatment and confirmed from a separate blood draw within 2 weeks; or virologic breakthrough which is confirmed HCV RNA ≥LLOQ (target detected, quantifiable [TD(q)]) after being <LLOQ previously while on treatment. Confirmation is defined as an HCV RNA ≥LLOQ from a separate blood draw repeated within 2 weeks; or relapse post-treatment. where there is a confirmed HCV RNA ≥LLOQ [TD(q)] following end of all study therapy, after becoming undetectable (target not detected [TND]) at end of treatment. Confirmation is defined as an HCV RNA ≥LLOQ from a separate blood draw repeated within 2 weeks.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2016)
  • Percentage of Participants With SVR 24 Weeks After Completing Study Therapy (SVR24) [ Time Frame: 24 weeks after completing study therapy (Week 36) ]
  • Percentage of Participants With Virologic Failure [ Time Frame: Up to Week 24 ]
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 Uprifosbuvir (MK-3682) + Ruzasvir (MK-8408) in Treating Hepatitis C Virus Infection Genotypes 1-6 (MK-3682-041)
Official Title  ICMJE A Phase 2, Open-Label Clinical Trial to Study the Efficacy and Safety of 12 Weeks of the Combination Regimen of MK-3682 + Ruzasvir in Subjects With Chronic Hepatitis C Virus (HCV) Genotype 1, 2, 3, 4, 5 or 6 Infection
Brief Summary This is a nonrandomized, multi-site, open-label trial to evaluate a novel two-drug combination regimen (uprifosbuvir [MK-3682] 450 mg + ruzasvir [RZR; MK-8408] 180 mg once daily [q.d.] for 12 weeks) in male and female treatment-naïve (TN) or treatment-experienced (TE) participants with chronic hepatitis C virus (HCV) infection genotype (GT) GT1, GT2, GT3, GT4, GT5, or GT6 who have not previously received HCV direct-acting antiviral (DAA) therapy. Cirrhotic (C) and non-cirrhotic (NC) participants with and without human immunodeficiency virus (HIV) co-infection will be enrolled.
Detailed Description Any GT that meets virologic futility criteria will be given the option of extending treatment with uprifosbuvir + RZR to 16 weeks with ribavirin (RBV) added.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE
  • Drug: Uprifosbuvir
    Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.
    Other Name: MK-3682
  • Drug: Ruzasvir
    Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.
    Other Name: MK-8408
  • Drug: Ribavirin
    RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.
Study Arms  ICMJE
  • Experimental: HCV GT1
    Male and female participants with HCV GT1a or GT1b infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
    Interventions:
    • Drug: Uprifosbuvir
    • Drug: Ruzasvir
    • Drug: Ribavirin
  • Experimental: HCV GT2
    Male and female participants with HCV GT2 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
    Interventions:
    • Drug: Uprifosbuvir
    • Drug: Ruzasvir
    • Drug: Ribavirin
  • Experimental: HCV GT3
    Male and female participants with HCV GT3 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
    Interventions:
    • Drug: Uprifosbuvir
    • Drug: Ruzasvir
    • Drug: Ribavirin
  • Experimental: HCV GT4
    Male and female participants with HCV GT4 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
    Interventions:
    • Drug: Uprifosbuvir
    • Drug: Ruzasvir
    • Drug: Ribavirin
  • Experimental: HCV GT5
    Male and female participants with HCV GT5 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
    Interventions:
    • Drug: Uprifosbuvir
    • Drug: Ruzasvir
    • Drug: Ribavirin
  • Experimental: HCV GT6
    Male and female participants with HCV GT6 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
    Interventions:
    • Drug: Uprifosbuvir
    • Drug: Ruzasvir
    • Drug: Ribavirin
Publications * Lawitz E, Gane E, Feld JJ, Buti M, Foster GR, Rabinovitz M, Burnevich E, Katchman H, Tomasiewicz K, Lahser F, Jackson B, Shaughnessy M, Klopfer S, Yeh WW, Robertson MN, Hanna GJ, Barr E, Platt HL; C-BREEZE-2 Study Investigators. Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6. J Viral Hepat. 2019 Sep;26(9):1127-1138. doi: 10.1111/jvh.13132. Epub 2019 Jul 11.

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: January 7, 2018)
282
Original Estimated Enrollment  ICMJE
 (submitted: November 3, 2016)
250
Actual Study Completion Date  ICMJE March 5, 2018
Actual Primary Completion Date December 22, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • has HCV ribonucleic acid (RNA) (≥10,000 IU/mL in peripheral blood) at the time of screening
  • has documented chronic HCV GT1, GT2, GT3, GT4, GT5, or GT6 (with no evidence of non-typeable or mixed GT)
  • is a female who is not of reproductive potential, or is a female of reproductive potential who agrees to avoid becoming pregnant from two weeks prior to Day 1 through 14 days after the last dose of study drug via abstinence or use of two approved contraceptives
  • is C or NC
  • if coinfected with HIV, has documented HIV infection prior to Day 1, and either does not use an antiretroviral therapy (ART) or has well-controlled HIV on stable ART (at least 4 weeks prior to study entry)

Exclusion Criteria:

  • has evidence of decompensated liver disease
  • is C and is Child-Pugh Class B or C, or has a Child-Tucotte-Pugh score >6
  • is coinfected with hepatitis B virus (hepatitis B surface antigen or hepatitis B core antibody positive)
  • is coinfected with HIV and has a recent (within 6 months prior to screening) opportunistic infection
  • has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ within 5 years of signing informed consent
  • is C and has evidence (liver imaging within 6 months prior to Day 1) of hepatocellular carcinoma (HCC) or is under evaluation for HCC
  • has participated in another investigational drug study within 30 days of signing informed consent
  • is a female who is pregnant or breastfeeding or expecting to conceive or donate eggs from Day 1 through 6 months after the last dose of study drug or longer if dictated by local regulations, or is a male who is expecting to donate sperm from Day 1 through 14 days after the last dose of study drug or longer if dictated by local regulations, or is a male whose female partner(s) is/are pregnant or breastfeeding
  • has clinically relevant alcohol or drug abuse within 12 months of screening
  • has any of the following conditions: organ transplants other than cornea and hair; poor venous access; history of gastric surgery; clinically significant cardiac abnormality/dysfunction; any major medical condition which, in the opinion of the investigator, might interfere with participation; hospitalization within 3 months prior to enrollment; any condition that might require hospitalization; any condition requiring or likely to require chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or immunosuppressant drugs; a life-threatening SAE during screening; or hepatitis not caused by HCV
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,   Canada,   Israel,   New Zealand,   Poland,   Russian Federation,   South Africa,   Spain,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02956629
Other Study ID Numbers  ICMJE 3682-041
2016-003227-37 ( EudraCT Number )
MK-3682-041 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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 June 2019

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