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Trial record 1 of 1 for:    nct02613403
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Efficacy and Safety of Grazoprevir (+) Uprifosbuvir (+) Ruzasvir (MK-3682B) (MK-5172 + MK-3682 + MK-8408) Fixed Dose Combination in Chronic HCV Participants Failing Prior Antiviral Treatment (MK-3682-021)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02613403
First Posted: November 24, 2015
Last Update Posted: October 24, 2017
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.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose

This is a randomized, multicenter, open-label trial of the combination regimen of grazoprevir (GZR; MK-5172) (100 mg), uprifosbuvir (UPR; MK-3682) (450 mg) and ruzasvir (RZR; MK-8408) (60 mg) for 16 weeks with ribavirin (RBV) or 24 weeks without RBV in cirrhotic (C) or non-cirrhotic (NC) hepatitis C virus (HCV) genotype (GT) 1-6 -infected participants who have previously failed a direct-acting antiviral regimen (DAA). The combination regimen will be administered as two fixed-dose combination (FDC) tablets, referred to as Grazoprevir (+) Uprifosbuvir (+) Ruzasvir (MK-3682B), given once-daily.

The study will evaluate the efficacy of the combination regimen of GZR (MK-5172), UPR (MK-3682) and RZR (MK-8408) with or without RBV as assessed by the proportion of participants achieving Sustained Virologic Response 12 weeks (SVR12) after the end of all study therapy.


Condition Intervention Phase
Hepatitis Hepatitis C Digestive System Diseases Flaviviridae Infections Hepatitis, Viral, Human Liver Diseases RNA Virus Infections Virus Diseases Drug: Grazoprevir+Uprifosbuvir+Ruzasvir Drug: Ribavirin Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in Subjects With Chronic HCV GT1 or GT3 Infection Who Have Failed a Direct Acting Antiviral Regimen

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12) [ Time Frame: 12 weeks after the end of study therapy: Week 28 for MK-3682B + RBV Groups; Week 36 for MK-3682B Groups ]
  • Number of participants who experienced at least one adverse event [ Time Frame: Up to Week 40 for MK-3682B + RBV Groups; up to Week 48 for MK-3682B Groups ]
  • Number of participants who discontinued study drug due to an adverse event [ Time Frame: Up to Week 16 for MK-3682B + RBV Groups and up to Week 24 for MK-3682B Groups ]
  • Number of participants who experienced at least one serious adverse event [ Time Frame: Up to Week 40 for MK-3682B + RBV Groups; up to Week 48 for MK-3682B Groups ]
  • Number of participants who experienced at least one drug-related adverse event [ Time Frame: Up to Week 40 for MK-3682B + RBV Groups; up to Week 48 for MK-3682B Groups ]
  • Number of participants who experienced at least one serious and drug-related adverse event [ Time Frame: Up to Week 40 for MK-3682B + RBV Groups; up to Week 48 for MK-3682B Groups ]
  • Number of participants who experienced at least one laboratory adverse event of interest [ Time Frame: Up to Week 40 for MK-3682B + RBV Groups; up to Week 48 for MK-3682B Groups ]
  • Number of participants who experienced AST/ALT >5 x upper limit normal at Week 4 or later [ Time Frame: From Week 4 up to Week 40 for MK-3682B + RBV Groups; from Week 4 up to Week 48 for MK-3682B Groups ]

Enrollment: 94
Actual Study Start Date: December 10, 2015
Study Completion Date: March 27, 2017
Primary Completion Date: January 9, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pt A: GT1 SOF/LDV failure: GZR + UPR + RZR (FDC) + RBV
C or NC HCV GT1 participants previously failing a sofosbuvir (SOF)/ledipasvir (LDV) DAA regimen will receive treatment with GZR + UPR + RZR (MK-5172 [50 mg] + MK-3682 [225 mg] + MK-8408 [30 mg] FDC) 2 tablets once daily + RBV twice daily for 16 weeks.
Drug: Grazoprevir+Uprifosbuvir+Ruzasvir
Two MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth.
Other Name: MK-3682B
Drug: Ribavirin
Two to three Ribavirin 200 mg (800 or 1000 or 1200 or 1400 mg total daily dose) capsules taken twice daily by mouth as part of a weight-based dosing regimen.
Experimental: Pt A: GT1 SOF/LDV failure: GZR + UPR + RZR (FDC)
C or NC HCV GT1 participants previously failing an SOF/LDV DAA regimen will receive treatment with GZR + UPR + RZR (MK-5172 [50 mg] + MK-3682 [225 mg] + MK-8408 [30 mg] FDC) 2 tablets once daily for 24 weeks.
Drug: Grazoprevir+Uprifosbuvir+Ruzasvir
Two MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth.
Other Name: MK-3682B
Experimental: Pt A: GT1 GZR/EBR failure: GZR + UPR + RZR (FDC) + RBV
C or NC HCV GT1 participants previously failing an MK-5172/MK-8742 (GZR/elbasvir [EBR]) DAA regimen will receive treatment with GZR + UPR + RZR (MK-5172 [50 mg] + MK-3682 [225 mg] + MK-8408 [30 mg] FDC) 2 tablets once daily + RBV twice daily for 16 weeks.
Drug: Grazoprevir+Uprifosbuvir+Ruzasvir
Two MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth.
Other Name: MK-3682B
Drug: Ribavirin
Two to three Ribavirin 200 mg (800 or 1000 or 1200 or 1400 mg total daily dose) capsules taken twice daily by mouth as part of a weight-based dosing regimen.
Experimental: Pt A: GT1 GZR/EBR failure: GZR + UPR + RZR (FDC)
C or NC HCV GT1 participants previously failing an MK-5172/MK-8742 (GZR/EBR) DAA regimen will receive treatment with GZR + UPR + RZR (MK-5172 [50 mg] + MK-3682 [225 mg] + MK-8408 [30 mg] FDC) 2 tablets once daily for 24 weeks.
Drug: Grazoprevir+Uprifosbuvir+Ruzasvir
Two MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth.
Other Name: MK-3682B
Experimental: Pt B: GT1-6 DAA failure; GT3 SOF/PR failure: GZR+UPR+RZR (FDC)
C or NC HCV GT1, GT2, GT3, GT4, GT5, or GT6 participants previously failing any all-oral DAA regimen or GT3 participants previously failing any all-oral DAA or SOF/pegylated interferon and ribavirin (PR) regimen will receive treatment with GZR + UPR + RZR (MK-5172 [50 mg] + MK-3682 [225 mg] + MK-8408 [30 mg] FDC) 2 tablets once daily for 16 weeks. Participants previously failing a regimen that included a nonstructural protein 3 (NS3)/4A protease inhibitor, NS5A inhibitor, and nucleotide analogue NS5B polymerase inhibitor may receive treatment with GZR + UPR + RZR (MK-5172 [50 mg] + MK-3682 [225 mg] + MK-8408 [30 mg] FDC) 2 tablets once daily for an extended period of 24 weeks.
Drug: Grazoprevir+Uprifosbuvir+Ruzasvir
Two MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth.
Other Name: MK-3682B

Detailed Description:
Prior to enrollment of GT3-infected subjects, the safety and efficacy data for GT3 subjects being dosed in Part B of MK-3682-012 (NCT02332720) will be reviewed. Participants in MK-5172-017 (NCT01667081) are eligible for enrollment in the study.
  Eligibility

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.


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

Inclusion Criteria:

  • Has HCV RNA ≥ 10,000 IU/mL in peripheral blood at enrollment.
  • Pt A: Has documented chronic HCV GT1 or HCV GT3 infection (with no evidence of non-typeable or mixed genotype). Pt B: Has documented chronic HCV GT1, GT2, GT3, GT4, GT5, GT6 infection (with no evidence of non-typeable or mixed genotype.
  • Pt A: Has documented relapse, defined as having HCV RNA target not detected at end-of-treatment, but HCV RNA quantifiable during follow-up, after treatment with one of the following DAA regimens either by approved dosage and duration or by completion of a clinical trial: GT1: SOF/LDV ± RBV; GT1: GZR/EBR ± RBV; GT3: SOF + RBV; GT3: SOF + PR; GT3: SOF + DCV ± RBV; GT3: SOF/LDV ± RBV. Participants who previously failed PR treatment, with or without simepravir (SIM), boceprevir (BOC), or telaprevir (TPV), prior to receiving DAA therapy, may also be enrolled. Pt B: Has documented virologic failure defined as having quantifiable HCV RNA at any time after completion of HCV therapy with a DAA regimen either by approved dosage and duration or by completion of a clinical trial that was not attributed to re-infection: GT1, GT2, GT4, GT5, or GT6: any prior all-oral DAA regimens; GT3: any prior all-oral DAA regimen or SOF/PR. Participants who previously failed PR treatment, with or without SIM, BOC, or TPV, prior to receiving DAA therapy, may also be enrolled.
  • Is otherwise healthy.
  • Has either absence of cirrhosis or presence of compensated cirrhosis.
  • Is not of reproductive potential or is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug, through 6 months after taking the last dose of study drug (or longer if dictated by local regulations), by complying with one of the following: (1) practice abstinence from heterosexual activity OR (2) use (or have their partner use) two forms of acceptable contraception during heterosexual activity which may include oral contraceptives (Pt A); acceptable contraception during heterosexual activity which may include oral contraceptives (Pt B).
  • For HIV co-infected participants additional criteria include: 1) documented HIV-1 infection (Pt A); HIV infection (Pt B), 2) either not currently on antiretroviral therapy (ART) without plans to initiate ART while participating in this study or has well controlled HIV on ART 3) at least one viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of anti-retroviral drug resistance (Pt A).

Exclusion Criteria:

  • Is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures.
  • Has previously received a DAA containing regimen other than the permitted regimens listed above (Pt A).
  • Did not complete their prior DAA therapy due to intolerance to the DAA regimen or who failed the DAA regimen for reasons other than relapse (e.g., virologic breakthrough, rebound or non-response, non-compliance, lost to follow-up, withdrew consent) (Pt A) or virologic failure (Pt B).
  • 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.
  • Has cirrhosis classified as Child-Pugh Class B or C or has a Pugh-Turcotte (CPT) score >6
  • Is coinfected with hepatitis B virus (HBV)
  • For participants with HIV, has a history of opportunistic infection in the 6 months prior to screening.
  • Has a history of malignancy ≤5 years prior to enrollment except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy.
  • Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
  • Is currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study (trial treatment period). Participants participating in MK-5172-017 (NCT01667081) may be enrolled in this study, MK- 3682-021.
  • Has clinically-relevant drug or alcohol abuse within 12 months of screening
  • Is a female and is pregnant or breastfeeding or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 through at least 6 months (Pt A) or 14 days (Pt B) after last dose of study drug, or longer if dictated by local regulations.
  • Is a male whose female partner(s) is/are pregnant.
  • Has organ transplants (including hematopoietic stem cell transplants) other than cornea and hair.
  • Has history of gastric surgery or history of malabsorption disorders.
  • Has current or history of any clinically significant cardiac abnormalities/dysfunction or personal or family history of Torsade de pointes.
  • Has chronic pulmonary disease (Pt A).
  • Has an hemoglobinopathy (Pt A).
  • Has central nervous system (CNS) trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, or resulting in seizure, coma, permanent neurologic deficits, abnormal brain imaging, or cerebral spinal fluid (CSF) leak; prior brain hemorrhage and/or intracranial aneurysms (whether adequately repaired or not) (Pt A).
  • Has current or history of seizure disorder unless seizure was >10 years ago, a single isolated event, no history of or current use of anti-seizure medications, and a documented normal neurological examination at Day 1 (Pt A).
  • Has history of stroke or transient ischemic attack (Pt A).
  • Has any major medical condition, clinically-significant illness (other than HCV), pretrial laboratory or ECG abnormality, or history of any illness that might interfere with treatment, assessment, compliance or pose additional risk in administering study drug to the participant (Pt B).
  • Has medical/surgical conditions that may result in a need for hospitalization during the period of the study.
  • Has a medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, TNF antagonists, or other immunosuppressant drugs during the course of the study
  • Has evidence of history of chronic hepatitis not caused by HCV. Participants with history of acute non-HCV-related hepatitis, that resolved >6 months before study entry, may be enrolled.
  Contacts and Locations
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): NCT02613403


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: NCT02613403     History of Changes
Other Study ID Numbers: 3682-021
2015-001483-19 ( EudraCT Number )
First Submitted: November 20, 2015
First Posted: November 24, 2015
Last Update Posted: October 24, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Virus Diseases
Digestive System Diseases
Gastrointestinal Diseases
RNA Virus Infections
Hepatitis, Viral, Human
Flaviviridae Infections
Enterovirus Infections
Picornaviridae Infections
Ribavirin
Antiviral Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents