Efficacy and Safety of Grazoprevir (MK-5172) and Uprifosbuvir (MK-3682) With Elbasvir (MK-8742) or Ruzasvir (MK-8408) for Chronic Hepatitis C Virus (HCV) Genotype (GT) 3, GT4, GT5, and GT6 Infection (MK-3682-012)

NCT ID: NCT02332720

Last Updated: 2019-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 413 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-28
• Study Completion Date: 2017-05-03

Brief Summary

This is a randomized, three-part, parallel-group, open-label trial of grazoprevir (MK-5172) (100 mg) and uprifosbuvir (MK-3682) (300 mg or 450 mg) with either elbasvir (MK-8742) (50 mg) or ruzasvir (MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naive (TN) or treatment-experienced (TE) cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) genotype (GT) 3, GT4, GT5, or GT6. Part A will consist of 4 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 uprifosbuvir (+) grazoprevir (+) ruzasvir (MK-3682B) fixed dose combination (FDC) tablets once daily (q.d.) by mouth, with or without twice-daily (b.i.d.) RBV (200 mg capsules; weight-based dosing). Participants who relapse following completion of therapy in Part A will be offered the option of retreatment with 16 weeks of uprifosbuvir (+) grazoprevir (+) ruzasvir with RBV in Part C (data obtained from Part C will not be used in the analysis of outcome measures).

Detailed Description

In Part A, study therapy will be administered as separate products, each taken q.d. by mouth. In Part B and Part C, participants will take 2 uprifosbuvir (+) grazoprevir (+) ruzasvir FDC tablets q.d. by mouth; each uprifosbuvir (+) grazoprevir (+) ruzasvir FDC tablet contains grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg.

Conditions

Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 weeks)

In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

Part A: one grazoprevir 100 mg tablet taken q.d. by mouth.

Uprifosbuvir

Intervention Type: DRUG

Part A: two or three uprifosbuvir 150 mg (300 or 450 mg total daily dose) tablets taken q.d. by mouth.

Elbasvir

Intervention Type: DRUG

Part A: one elbasvir 50 mg tablet taken q.d. by mouth.

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 weeks)

In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

Part A: one grazoprevir 100 mg tablet taken q.d. by mouth.

Uprifosbuvir

Intervention Type: DRUG

Part A: two or three uprifosbuvir 150 mg (300 or 450 mg total daily dose) tablets taken q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Part A: six ruzasvir 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 weeks)

In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

Part A: one grazoprevir 100 mg tablet taken q.d. by mouth.

Uprifosbuvir

Intervention Type: DRUG

Part A: two or three uprifosbuvir 150 mg (300 or 450 mg total daily dose) tablets taken q.d. by mouth.

Elbasvir

Intervention Type: DRUG

Part A: one elbasvir 50 mg tablet taken q.d. by mouth.

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

A4/B4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 weeks)

Participants will be randomized to either Part A or Part B. In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (450 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

Part A: one grazoprevir 100 mg tablet taken q.d. by mouth.

Uprifosbuvir

Intervention Type: DRUG

Part A: two or three uprifosbuvir 150 mg (300 or 450 mg total daily dose) tablets taken q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Part A: six ruzasvir 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B5: GT3 NC TN MK-3682B + RBV (8 weeks)

In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B6: GT3 NC TN MK-3682B (12 weeks)

In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B7: GT3 NC TN MK-3682B + RBV (12 weeks)

In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B8: GT3 NC TE MK-3682B (8 weeks)

In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B9: GT3 NC TE MK-3682B + RBV (8 weeks)

In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B10: GT3 NC TE MK-3682B (12 weeks)

In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B11: GT3 NC TE MK-3682B + RBV (12 weeks)

In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B12: GT3 NC TE MK-3682B (16 weeks)

In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B13: GT3 C TN MK-3682B (12 weeks)

In Part B, HCV GT3-infected C TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B14: GT3 C TN MK-3682B + RBV (12 weeks)

In Part B, HCV GT3-infected C TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B15: GT3 C TN MK-3682B (16 weeks)

In Part B, HCV GT3-infected C TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B16: GT3 C TE MK-3682B (12 weeks)

In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B17: GT3 C TE MK-3682B + RBV (12 weeks)

In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B18: GT3 C TE MK-3682B (16 weeks)

In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B19: GT3 C TE MK-3682B + RBV (16 weeks)

In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Ribavirin (RBV)

Intervention Type: DRUG

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

B20: GT4 NC TN MK-3682B (8 weeks)

In Part B, HCV GT4-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B21: GT5 NC TN MK-3682B (12 weeks)

In Part B, HCV GT5-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

B22: GT6 NC TN MK-3682B (12 weeks)

In Part B, HCV GT6-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

MK-3682B

Intervention Type: DRUG

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Interventions

Grazoprevir

Part A: one grazoprevir 100 mg tablet taken q.d. by mouth.

Intervention Type: DRUG

Uprifosbuvir

Part A: two or three uprifosbuvir 150 mg (300 or 450 mg total daily dose) tablets taken q.d. by mouth.

Intervention Type: DRUG

Elbasvir

Part A: one elbasvir 50 mg tablet taken q.d. by mouth.

Intervention Type: DRUG

Ruzasvir

Part A: six ruzasvir 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.

Intervention Type: DRUG

MK-3682B

Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.

Intervention Type: DRUG

Ribavirin (RBV)

Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.

Intervention Type: DRUG

Other Intervention Names

MK-5172; MK-3682; MK-8742; MK-8408; Rebetol

Eligibility Criteria

Inclusion Criteria

• Has documented chronic HCV GT3, GT4, GT5, or GT6 with no evidence of non-typeable or mixed GT infection
• Is otherwise healthy as determined by the medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements performed at the time of screening
• Has cirrhosis of the liver (Part B only) or is non-cirrhotic (Part A and B)
• Is HCV treatment-naïve or has experienced virologic failure after completing a prior Pegylated Interferon/Ribavirin (Peg-IFN/RBV) regimen
• Is of non childbearing potential or agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug and for 14 days after the last dose of study drug if not taking RBV, or for 6 months after the last dose of study drug if taking RBV (or longer if dictated by local regulations). If not abstinent from heterosexual activity, participants in Part A must use 2 acceptable forms of barrier contraception whereas participants in Parts B and C must use 2 acceptable forms of contraception which may include oral contraceptives

Part B only:

• If coinfected with human immunodeficiency virus (HIV) is not currently on antiretroviral therapy (ART) and has no plans to initiate ART treatment while participating in this study OR has well-controlled HIV on ART.
• Has at least 1 viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of anti-retroviral drug resistance.

Exclusion Criteria

Parts A, B, and C (unless otherwise specified):

• 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.
• If cirrhotic (Part B only), is Child-Pugh Class B or C or has a Pugh-Turcotte (CPT) score >5.
• Is coinfected with hepatitis B virus (Parts A, B, and C) or is coinfected with HIV (Part A only; HIV coinfected participants are eligible for Parts B and C).
• If coinfected with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening.
• Has a history of malignancy ≤5 years prior to signing informed consent 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.
• Has clinically-relevant drug or alcohol abuse within 12 months of screening.
• Is female and is pregnant or breastfeeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and 6 months after the last dose of study medication, or longer if dictated by local regulations OR a male participant who is expecting to donate sperm from at least 2 weeks prior to day 1 until 6 months after the last dose of study medication.
• Has any of the following conditions:
• Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair.
• Poor venous access that precludes routine peripheral blood sampling required for this trial.
• History of gastric surgery (e.g., stapling, bypass) or a history of malabsorption disorders (e.g., celiac sprue disease).
• Current or history of any clinically significant cardiac abnormalities/dysfunction, including but not limited to: angina, congestive heart failure, myocardial infarction, pulmonary hypertension, complex congenital heart disease, cardiomyopathy, significant arrhythmia, uncontrolled hypertension, a history of use of antianginal or anti-arrythmic agents for cardiac conditions, prolonged ECG QTc interval (>470 ms for males or >480 ms for females by either the Fridericia formula) at the screening visit, personal or family history of Torsade de pointes.
• Chronic pulmonary disease, including but not limited to: clinically significant chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis.
• 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).
• 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 prescribed, and a normal neurological examination is documented in trial files within 6 months of Day 1.
• Has a history of stroke or transient ischemic attack.
• Has a history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures.
• Has medical/surgical conditions that may result in a need for hospitalization during the period of the study.
• Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial.
• Has any condition, prestudy laboratory or ECG abnormality or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the participant.
• Has had a life-threatening serious adverse event (SAE) during the screening period.
• Has evidence of history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, alcoholic liver disease and autoimmune hepatitis Parts B and C only: is a male whose female partner(s) is/are pregnant

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Lawitz E, Buti M, Vierling JM, Almasio PL, Bruno S, Ruane PJ, Hassanein TI, Muellhaupt B, Pearlman B, Jancoriene L, Gao W, Huang HC, Shepherd A, Tannenbaum B, Fernsler D, Li JJ, Grandhi A, Liu H, Su FH, Wan S, Dutko FJ, Nguyen BT, Wahl J, Robertson MN, Barr E, Yeh WW, Plank RM, Butterton JR, Yoshida EM. Safety and efficacy of a fixed-dose combination regimen of grazoprevir, ruzasvir, and uprifosbuvir with or without ribavirin in participants with and without cirrhosis with chronic hepatitis C virus genotype 1, 2, or 3 infection (C-CREST-1 and C-CREST-2, part B): two randomised, phase 2, open-label trials. Lancet Gastroenterol Hepatol. 2017 Nov;2(11):814-823. doi: 10.1016/S2468-1253(17)30163-2. Epub 2017 Aug 10.

Reference Type: RESULT

PMID: 28802814 (View on PubMed)

Gane EJ, Pianko S, Roberts SK, Thompson AJ, Zeuzem S, Zuckerman E, Ben-Ari Z, Foster GR, Agarwal K, Laursen AL, Gerstoft J, Gao W, Huang HC, Fitzgerald B, Fernsler D, Li JJ, Grandhi A, Liu H, Su FH, Wan S, Zeng Z, Chen HL, Dutko FJ, Nguyen BT, Wahl J, Robertson MN, Barr E, Yeh WW, Plank RM, Butterton JR, Esteban R. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A): two randomised, phase 2, open-label trials. Lancet Gastroenterol Hepatol. 2017 Nov;2(11):805-813. doi: 10.1016/S2468-1253(17)30159-0. Epub 2017 Aug 10.

Reference Type: DERIVED

PMID: 28802816 (View on PubMed)

Other Identifiers

2014-003347-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3682-012

Identifier Type: -

Identifier Source: org_study_id