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Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic Hepatitis C Virus (HCV) Genotype 3 (GT3) Infection (MK-5172-083)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02601573
Collaborator
(none)
101
Enrollment
5
Arms
12.1
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This is a randomized, multi-site, open-label trial of the co-administration of a fixed-dose combination (FDC) of EBR 50 mg + GZR (100 mg) (EBR/GZR) and SOF 400 mg, with and without RBV, in treatment-naïve (TN) and treatment-experienced (TE) participants with chronic HCV GT3 infection with compensated cirrhosis.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
101 participants
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 Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic HCV GT3 Infection
Actual Study Start Date :
Jan 5, 2016
Actual Primary Completion Date :
Oct 18, 2016
Actual Study Completion Date :
Jan 6, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks

TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks.

Drug: Grazoprevir
GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-5172

    • Drug: Elbasvir
    EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-8742

    • Drug: Ribavirin
    RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight).
    Other Names:
  • Rebetol®

    • Drug: Sofosbuvir
    SOF 400 mg tablet taken q.d. by mouth in the morning with food.
    Other Names:
  • Sovaldi®, Harvoni®

    		•
    Experimental: Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks

    TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.

    Drug: Grazoprevir
    GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-5172

    • Drug: Elbasvir
    EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-8742

    • Drug: Sofosbuvir
    SOF 400 mg tablet taken q.d. by mouth in the morning with food.
    Other Names:
  • Sovaldi®, Harvoni®

    		•
    Experimental: Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks

    TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.

    Drug: Grazoprevir
    GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-5172

    • Drug: Elbasvir
    EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-8742

    • Drug: Sofosbuvir
    SOF 400 mg tablet taken q.d. by mouth in the morning with food.
    Other Names:
  • Sovaldi®, Harvoni®

    		•
    Experimental: Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks

    TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks.

    Drug: Grazoprevir
    GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-5172

    • Drug: Elbasvir
    EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-8742

    • Drug: Ribavirin
    RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight).
    Other Names:
  • Rebetol®

    • Drug: Sofosbuvir
    SOF 400 mg tablet taken q.d. by mouth in the morning with food.
    Other Names:
  • Sovaldi®, Harvoni®

    		•
    Experimental: Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks

    TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.

    Drug: Grazoprevir
    GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-5172

    • Drug: Elbasvir
    EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
    Other Names:
  • MK-8742

    • Drug: Sofosbuvir
    SOF 400 mg tablet taken q.d. by mouth in the morning with food.
    Other Names:
  • Sovaldi®, Harvoni®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving SVR12 (Sustained Virologic Response 12 Weeks After the End of All Study Therapy) [Up to Week 28]

      The percentage of participants achieving SVR12 (i.e., HCV ribnonucleic acid [RNA] < Lower Limit of Quantification [LLOQ] 12 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.

    2. Percentage of Participants Experiencing an Adverse Event (AE) [Up to 18 weeks (up to 2 weeks after completion of study treatment)]

      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.

    3. Percentage of Participants Discontinuing From Study Therapy Due to an AE [Up to 16 weeks]

      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.

    Secondary Outcome Measures

    1. Percentage of Participants Achieving SVR24 (Sustained Virologic Response 24 Weeks After the End of All Study Therapy) [Up to Week 40]

      The percentage of participants achieving SVR24 (i.e., HCV RNA < LLOQ 24 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • has HCV RNA (>= 10,000 IU/mL in peripheral blood) at screening

    • has documented HCV GT3 (with no evidence of non-typeable or mixed GT infection)

    • has compensated cirrhosis of the liver

    • has liver imaging within 6 months of Day 1 with no evidence of hepatocellular carcinoma (HCC)

    • is either HCV TN or TE (i.e., has documented prior virologic failure or intolerance to peg-interferon/ribavirin)

    • is otherwise healthy as determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements

    • has compensated cirrhosis of the liver

    • is TN or TE (i.e., documented prior virologic failure or intolerance to peg-interferon/ribavirin)

    • is not of reproductive potential, or agrees to not impregnate a partner or become pregnant for at least 2 weeks prior to the first dose of study drug, and for 7 months after the final dose of study drug (or longer if dictated by local regulations)

    Exclusion Criteria:

    • has previously received one or more doses of a direct-acting antiviral (DAA)

    • has evidence of decompensated liver disease

    • is coinfected with hepatitis B (hepatitis B surface antigen [HBsAg] positive)

    • has a recent (within 5 years) history of malignancy or is under evaluation for HCC or other suspected malignancy

    • is currently or has participated (within past 30 days) in a study with an investigational compound

    • has clinically-relevant drug or alcohol abuse within the past 12 months of screening

    • is a female and is pregnant or breast-feeding

    • is a male whose female partner is/are pregnant

    • has any of the following:

    • organ transplants

    • poor venous access

    • history of gastric surgery or malabsorption disorder

    • current or history of clinically significant cardiac abnormalities or dysfunction

    • chronic pulmonary disease

    • hemoglobinopathy

    • history of hospitalization within 3 months prior to enrollment

    • medical or surgical condition that may result in need for hospitalization during the course of the study

    • any condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppresant drugs during the course of the study

    • any condition, prestudy laboratory or ECG abnormality, or history of any illness, which could confound results of the study or pose additional risks in administering study drugs in the opinion of the investigator

    • has a life-threatening serious AE (SAE) during the screening period

    • has evidence of history of chronic hepatitis not caused by HCV

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02601573
    Other Study ID Numbers:
    • 5172-083
    • 2015-003187-37
    • MK-5172-083
    First Posted:
    Nov 10, 2015
    Last Update Posted:
    Aug 13, 2019
    Last Verified:
    Aug 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis
    Ribavirin
    Sofosbuvir
    Grazoprevir

    Study Results

    Participant Flow

    Recruitment Details Adult participants infected with HCV GT3 were enrolled at 14 study centers in the United Kingdom.
    Pre-assignment Detail A total of 101 participants were randomized, including 1 participant who did not meet inclusion criteria and who should have been considered a screen failure; this participant was not treated with study drug. A total of 100 participants were treated.
    Arm/Group Title Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Arm/Group Description Treatment-naïve (TN) Hepatitis C virus (HCV) genotype 3 (GT3) participants took 1 fixed-dose combination (FDC) tablet containing elbasvir (EBR) 50 mg + grazoprevir (GZR) 100 mg and 1 tablet containing sofosbuvir (SOF) 400 mg once daily (q.d.) with ribavirin (RBV) (200 mg capsules; weight-based dosing) twice daily (b.i.d.) for 8 weeks. TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. Treatment-experienced (TE) HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
    Period Title: Overall Study
    STARTED 23 24 17 18 18
    COMPLETED 23 20 16 17 16
    NOT COMPLETED 0 4 1 1 2

    Baseline Characteristics

    Arm/Group Title Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks Total
    Arm/Group Description TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 8 weeks. TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks. Total of all reporting groups
    Overall Participants 23 24 17 18 18 100
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    52.5
    (9.0)
    48.1
    (9.3)
    58.6
    (6.1)
    56.1
    (8.4)
    53.8
    (6.4)
    53.4
    (8.7)
    Sex: Female, Male (Count of Participants)
    Female
    10
    43.5%
    7
    29.2%
    6
    35.3%
    6
    33.3%
    3
    16.7%
    32
    32%
    Male
    13
    56.5%
    17
    70.8%
    11
    64.7%
    12
    66.7%
    15
    83.3%
    68
    68%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Achieving SVR12 (Sustained Virologic Response 12 Weeks After the End of All Study Therapy)
    Description The percentage of participants achieving SVR12 (i.e., HCV ribnonucleic acid [RNA] < Lower Limit of Quantification [LLOQ] 12 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.
    Time Frame Up to Week 28

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug, were not lost to follow-up for reasons unrelated to study treatment, and had SVR12 data available are included.
    Arm/Group Title Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Arm/Group Description TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 8 weeks. TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
    Measure Participants 23 23 17 17 18
    Number (95% Confidence Interval) [Percentage of Participants]
    91.3
    397%
    100.0
    416.7%
    100.0
    588.2%
    100.0
    555.6%
    94.4
    524.4%
    2. Primary Outcome
    Title Percentage of Participants Experiencing an Adverse Event (AE)
    Description 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.
    Time Frame Up to 18 weeks (up to 2 weeks after completion of study treatment)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug are included.
    Arm/Group Title Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Arm/Group Description TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 8 weeks. TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
    Measure Participants 23 24 17 18 18
    Number [Percentage of Participants]
    87.0
    378.3%
    87.5
    364.6%
    82.4
    484.7%
    94.4
    524.4%
    94.4
    524.4%
    3. Primary Outcome
    Title Percentage of Participants Discontinuing From Study Therapy Due to an AE
    Description 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.
    Time Frame Up to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug are included.
    Arm/Group Title Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Arm/Group Description TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 8 weeks. TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
    Measure Participants 23 24 17 18 18
    Number [Percentage of Participants]
    0.0
    0%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    5.6
    31.1%
    4. Secondary Outcome
    Title Percentage of Participants Achieving SVR24 (Sustained Virologic Response 24 Weeks After the End of All Study Therapy)
    Description The percentage of participants achieving SVR24 (i.e., HCV RNA < LLOQ 24 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.
    Time Frame Up to Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug, were not lost to follow-up for reasons unrelated to study treatment, and had SVR24 data available are included.
    Arm/Group Title Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Arm/Group Description TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 8 weeks. TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
    Measure Participants 23 21 16 17 16
    Number (95% Confidence Interval) [Percentage of Participants]
    91.3
    397%
    100.0
    416.7%
    100.0
    588.2%
    100.0
    555.6%
    93.8
    521.1%

    Adverse Events

    Time Frame Up to 40 weeks
    Adverse Event Reporting Description All participants who received at least 1 dose of study drug are included.
    Arm/Group Title Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Arm/Group Description TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 8 weeks. TN HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg + GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. TE HCV GT3 participants took 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
    All Cause Mortality
    Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/24 (0%) 2/17 (11.8%) 3/18 (16.7%) 1/18 (5.6%)
    General disorders
    Chest pain 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Infections and infestations
    Cellulitis 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Lung infection 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 2 0/18 (0%) 0 0/18 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Toxicity to various agents 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Wrist fracture 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Investigations
    Creatinine renal clearance decreased 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatocellular carcinoma 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/23 (91.3%) 21/24 (87.5%) 16/17 (94.1%) 17/18 (94.4%) 17/18 (94.4%)
    Cardiac disorders
    Palpitations 2/23 (8.7%) 2 0/24 (0%) 0 1/17 (5.9%) 1 1/18 (5.6%) 1 0/18 (0%) 0
    Ear and labyrinth disorders
    Ear pain 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 1/18 (5.6%) 1 0/18 (0%) 0
    Hypoacusis 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Eye disorders
    Dry eye 1/23 (4.3%) 1 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Lacrimation increased 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Myopia 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Vision blurred 0/23 (0%) 0 1/24 (4.2%) 1 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Visual impairment 0/23 (0%) 0 1/24 (4.2%) 1 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 2/23 (8.7%) 2 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Abdominal distension 0/23 (0%) 0 0/24 (0%) 0 3/17 (17.6%) 3 1/18 (5.6%) 2 0/18 (0%) 0
    Abdominal pain 0/23 (0%) 0 2/24 (8.3%) 2 1/17 (5.9%) 1 4/18 (22.2%) 4 1/18 (5.6%) 1
    Abdominal pain lower 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Abdominal pain upper 1/23 (4.3%) 1 2/24 (8.3%) 2 1/17 (5.9%) 1 0/18 (0%) 0 1/18 (5.6%) 1
    Ascites 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Constipation 1/23 (4.3%) 1 3/24 (12.5%) 3 1/17 (5.9%) 1 0/18 (0%) 0 1/18 (5.6%) 1
    Diarrhoea 1/23 (4.3%) 1 3/24 (12.5%) 4 3/17 (17.6%) 3 2/18 (11.1%) 2 3/18 (16.7%) 3
    Dry mouth 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 1/18 (5.6%) 1
    Dyspepsia 0/23 (0%) 0 1/24 (4.2%) 1 1/17 (5.9%) 1 1/18 (5.6%) 1 1/18 (5.6%) 1
    Flatulence 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Gastrooesophageal reflux disease 0/23 (0%) 0 1/24 (4.2%) 1 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Haemorrhoids 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Lip dry 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Mouth ulceration 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 2 0/18 (0%) 0 0/18 (0%) 0
    Nausea 4/23 (17.4%) 4 3/24 (12.5%) 3 3/17 (17.6%) 3 6/18 (33.3%) 7 3/18 (16.7%) 3
    Oesophagitis 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Toothache 1/23 (4.3%) 1 1/24 (4.2%) 1 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Vomiting 0/23 (0%) 0 3/24 (12.5%) 3 1/17 (5.9%) 1 1/18 (5.6%) 1 1/18 (5.6%) 1
    General disorders
    Chills 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 2/18 (11.1%) 2 1/18 (5.6%) 1
    Fatigue 6/23 (26.1%) 6 8/24 (33.3%) 10 6/17 (35.3%) 6 10/18 (55.6%) 10 6/18 (33.3%) 6
    Feeling hot 0/23 (0%) 0 1/24 (4.2%) 1 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Influenza like illness 0/23 (0%) 0 1/24 (4.2%) 1 0/17 (0%) 0 0/18 (0%) 0 2/18 (11.1%) 2
    Oedema peripheral 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Pain 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Pyrexia 0/23 (0%) 0 2/24 (8.3%) 2 1/17 (5.9%) 1 1/18 (5.6%) 2 1/18 (5.6%) 1
    Hepatobiliary disorders
    Biliary colic 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Jaundice 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 2/18 (11.1%) 2 0/18 (0%) 0
    Immune system disorders
    Hypersensitivity 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Seasonal allergy 1/23 (4.3%) 1 1/24 (4.2%) 1 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Infections and infestations
    Cellulitis 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Conjunctivitis 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Lower respiratory tract infection 1/23 (4.3%) 1 2/24 (8.3%) 2 1/17 (5.9%) 1 0/18 (0%) 0 1/18 (5.6%) 1
    Nasopharyngitis 1/23 (4.3%) 1 2/24 (8.3%) 2 1/17 (5.9%) 1 1/18 (5.6%) 1 2/18 (11.1%) 2
    Rhinitis 0/23 (0%) 0 2/24 (8.3%) 2 0/17 (0%) 0 0/18 (0%) 0 0/18 (0%) 0
    Upper respiratory tract infection 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 1/18 (5.6%) 1
    Urinary tract infection 0/23 (0%) 0 2/24 (8.3%) 2 0/17 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1
    Injury, poisoning and procedural complications
    Accidental overdose 1/23 (4.3%) 1 0/24 (0%) 0 2/17 (11.8%) 3 3/18 (16.7%) 4 0/18 (0%) 0
    Skin abrasion 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 2 0/18 (0%) 0
    Investigations
    Blood potassium increased 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Haemoglobin decreased 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 2/18 (11.1%) 2 0/18 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/23 (0%) 0 4/24 (16.7%) 4 0/17 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1
    Type 2 diabetes mellitus 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/23 (4.3%) 1 0/24 (0%) 0 2/17 (11.8%) 3 3/18 (16.7%) 3 2/18 (11.1%) 2
    Back pain 1/23 (4.3%) 1 2/24 (8.3%) 2 1/17 (5.9%) 1 1/18 (5.6%) 1 0/18 (0%) 0
    Bone pain 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Costochondritis 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Haemarthrosis 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Joint effusion 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Musculoskeletal chest pain 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Musculoskeletal discomfort 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Musculoskeletal pain 0/23 (0%) 0 1/24 (4.2%) 1 1/17 (5.9%) 1 1/18 (5.6%) 1 0/18 (0%) 0
    Myalgia 0/23 (0%) 0 1/24 (4.2%) 2 4/17 (23.5%) 5 2/18 (11.1%) 2 1/18 (5.6%) 1
    Neck pain 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Pain in extremity 2/23 (8.7%) 2 0/24 (0%) 0 4/17 (23.5%) 4 0/18 (0%) 0 1/18 (5.6%) 1
    Nervous system disorders
    Amnesia 1/23 (4.3%) 2 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Disturbance in attention 1/23 (4.3%) 1 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Dizziness 1/23 (4.3%) 1 3/24 (12.5%) 3 0/17 (0%) 0 3/18 (16.7%) 3 1/18 (5.6%) 1
    Dysgeusia 1/23 (4.3%) 1 1/24 (4.2%) 1 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Headache 5/23 (21.7%) 6 7/24 (29.2%) 7 5/17 (29.4%) 7 11/18 (61.1%) 12 7/18 (38.9%) 7
    Hypersomnia 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Hypoaesthesia 1/23 (4.3%) 1 0/24 (0%) 0 2/17 (11.8%) 3 0/18 (0%) 0 0/18 (0%) 0
    Lethargy 0/23 (0%) 0 1/24 (4.2%) 1 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Memory impairment 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Nystagmus 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Paraesthesia 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Sinus headache 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Syncope 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Tremor 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Psychiatric disorders
    Anxiety 2/23 (8.7%) 2 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 1/18 (5.6%) 1
    Depressed mood 0/23 (0%) 0 1/24 (4.2%) 1 0/17 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1
    Depression 0/23 (0%) 0 1/24 (4.2%) 1 1/17 (5.9%) 1 1/18 (5.6%) 1 0/18 (0%) 0
    Emotional disorder 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Euphoric mood 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Hallucination 0/23 (0%) 0 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Insomnia 2/23 (8.7%) 2 0/24 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Irritability 2/23 (8.7%) 2 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Mood swings 1/23 (4.3%) 1 0/24 (0%) 0 0/17 (0%) 0 3/18 (16.7%) 3 0/18 (0%) 0
    Panic attack 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Sleep disorder 1/23 (4.3%) 1 0/24 (0%) 0 2/17 (11.8%) 2 0/18 (0%) 0 0/18 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Reproductive system and breast disorders
    Nipple pain 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 1/23 (4.3%) 1 1/24 (4.2%) 1 1/17 (5.9%) 1 2/18 (11.1%) 2 1/18 (5.6%) 1
    Dysphonia 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Dyspnoea 1/23 (4.3%) 1 1/24 (4.2%) 1 1/17 (5.9%) 1 3/18 (16.7%) 3 0/18 (0%) 0
    Dyspnoea exertional 3/23 (13%) 3 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/18 (0%) 0
    Epistaxis 0/23 (0%) 0 0/24 (0%) 0 2/17 (11.8%) 2 1/18 (5.6%) 1 2/18 (11.1%) 2
    Oropharyngeal pain 1/23 (4.3%) 1 1/24 (4.2%) 1 1/17 (5.9%) 2 2/18 (11.1%) 2 4/18 (22.2%) 4
    Skin and subcutaneous tissue disorders
    Alopecia 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1
    Dry skin 2/23 (8.7%) 2 1/24 (4.2%) 1 1/17 (5.9%) 1 4/18 (22.2%) 4 1/18 (5.6%) 1
    Eczema 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Erythema 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Pruritus 0/23 (0%) 0 1/24 (4.2%) 1 1/17 (5.9%) 1 5/18 (27.8%) 6 1/18 (5.6%) 1
    Rash 3/23 (13%) 3 1/24 (4.2%) 1 1/17 (5.9%) 2 3/18 (16.7%) 3 1/18 (5.6%) 1
    Skin irritation 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Skin lesion 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Vascular disorders
    Hypertension 0/23 (0%) 0 1/24 (4.2%) 1 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0
    Peripheral coldness 0/23 (0%) 0 0/24 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02601573
    Other Study ID Numbers:
    • 5172-083
    • 2015-003187-37
    • MK-5172-083
    First Posted:
    Nov 10, 2015
    Last Update Posted:
    Aug 13, 2019
    Last Verified:
    Aug 1, 2019