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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 7, 2016
Results First Posted : December 25, 2018
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Uprifosbuvir Drug: Ruzasvir Drug: Ribavirin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 282 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 16, 2016
Actual Primary Completion Date : December 22, 2017
Actual Study Completion Date : March 5, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HCV GT1
Male and female participants with HCV GT1a or GT1b infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
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.

Experimental: HCV GT2
Male and female participants with HCV GT2 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
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.

Experimental: HCV GT3
Male and female participants with HCV GT3 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
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.

Experimental: HCV GT4
Male and female participants with HCV GT4 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
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.

Experimental: HCV GT5
Male and female participants with HCV GT5 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
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.

Experimental: HCV GT6
Male and female participants with HCV GT6 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.
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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02956629


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:

Publications of Results:
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02956629     History of Changes
Other Study ID Numbers: 3682-041
2016-003227-37 ( EudraCT Number )
MK-3682-041 ( Other Identifier: Merck Protocol Number )
First Posted: November 7, 2016    Key Record Dates
Results First Posted: December 25, 2018
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Uprifosbuvir
Ruzasvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents