Hepatitis C
Conditions
Brief summary
This is a randomized, three-part, open-label trial of grazoprevir (GZR; MK-5172) (100 mg) and uprifosbuvir (UPR; MK-3682) (300 mg or 450 mg), with either elbasvir (EBR; MK-8742) (50 mg) or ruzasvir (RZR; MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naïve (TN) cirrhotic (C) or non-cirrhotic (NC) hepatitis C virus (HCV) participants with chronic HCV genotype (GT) 1 or GT2 infection. Part A will consist of 8 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 UPR+GZR+RZR 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 UPR+GZR+RZR 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 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg q.d. by mouth.
Interventions
DRUGGrazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
DRUGUprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
DRUGElbasvir
One EBR 50 mg tablet (Part A), taken q.d. by mouth.
DRUGRuzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
DRUGUprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
DRUGRibavirin
RBV 200 mg capsules taken b.i.d. at a total daily dose of 800-1400 mg based on participant body weight.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Parts A and B: * Previously untreated chronic HCV GT1 or GT2 with no evidence of non-typeable or mixed genotype infection * Has HCV ribonucleic acid (RNA) \>= 10,000 IU/mL in peripheral blood at the time of screening * Is NC (Part A and B) * Is HCV treatment naïve (defined as no prior exposure to any interferon, ribavirin, or other approved or experimental HCV-specific direct-acting antiviral agent * 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 either 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 Part B must use 2 acceptable forms of contraception which may include oral contraceptives Part B only: * Has cirrhosis of the liver * 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 (the ART regimen must contain only the following antiretroviral medications: tenofovir, abacavir, lamivudine, emtricitabine, raltegravir, dolutegravir, and rilpivirine with no dose modifications or changes in drugs in the 4 weeks prior to study entry \[Day 1\]) * Has at least one viable ART regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of antiretroviral drug resistance
Exclusion criteria
Parts A, B, and C (unless noted otherwise): * 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 * For cirrhotics (Part B only), participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score \>5 * Is coinfected with hepatitis B virus * Is coinfected with HIV (Part A only) * If coinfected with HIV (Part B only), 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 has had 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 * Pregnant or breast-feeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and 90 days after the last dose of study medication, or longer if dictated by local regulations * 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 * has a history of gastric surgery (e.g., stapling, bypass) or 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-arrhythmic agents for cardiac conditions, prolonged electrocardiogram (ECG) QTc interval (\>470 ms for males or \>480 ms for females by 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) * a 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 * a history of stroke or transient ischemic attack * a history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures * a medical/surgical conditions that may result in a need for hospitalization during the period of the study * 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 subject * experiences a life-threatening serious adverse event (SAE) during the screening period * 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 * hemoglobinopathy, including, but not limited to, thalassemia major (Parts B and C only) Parts B and C only: is a male whose female partner(s) is/are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | Up to 28 weeks | The percentage of participants with Hepatitis C virus (HCV) ribonucleic acid (RNA) \< Lower Limit of Quantification (LLoQ) 12 weeks after completing treatment (i.e., SVR12) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL. |
| Percentage of Participants Experiencing an Adverse Event (AE) | Up to 18 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. |
| Percentage of Participants Discontinuing From Study Treatment 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | Up to 40 weeks | The percentage of participants with HCV RNA \< LLoQ 24 weeks after completing treatment (i.e., SVR24) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL. |
Participant flow
Recruitment details
This trial was conducted at 95 study sites in Asia, the European Union, and North America.
Pre-assignment details
The Number Started row reflects the number of randomized participants who received study treatment. A total of 443 participants were randomized but 1 participant withdrew consent prior to receiving any study treatment.
Participants by arm
| Arm | Count |
|---|---|
| A1: GT1 NC GZR+UPR+EBR (8 Weeks) In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. | 23 |
| A2: GT1 NC GZR+UPR+RZR (8 Weeks) In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. | 24 |
| A3: GT2 NC GZR+UPR+EBR (8 Weeks) In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. | 16 |
| A4: GT2 NC GZR+UPR+RZR (8 Weeks) In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. | 14 |
| A5: GT1 NC GZR+UPR+EBR (8 Weeks) In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. | 23 |
| A6: GT1 NC GZR+UPR+RZR (8 Weeks) In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. | 23 |
| A7: GT2 NC GZR+UPR+EBR (8 Weeks) In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. | 15 |
| A8: GT2 NC GZR+UPR+RZR (8 Weeks) In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. | 16 |
| B9: GT1 NC GZR+UPR+RZR (12 Weeks) In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. | 48 |
| B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight. | 31 |
| B11: GT2 NC GZR+UPR+RZR (12 Weeks) In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. | 31 |
| B12: GT1 C GZR+UPR+RZR (8 Weeks) In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. | 35 |
| B13: GT1 C GZR+UPR+RZR (12 Weeks) In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. | 40 |
| B14: GT2 C GZR+UPR+RZR (12 Weeks) In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. | 15 |
| B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight. | 16 |
| B16: GT2 C GZR+UPR+RZR (16 Weeks) In Part B, HCV GT2-infected C participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks. | 26 |
| B6: GT1 NC GZR+UPR+RVR (8 Weeks) In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. | 30 |
| B8: GT2 NC GZR+UPR+RZR (8 Weeks) In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. | 16 |
| Total | 442 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | A1: GT1 NC GZR+UPR+EBR (8 Weeks) | A2: GT1 NC GZR+UPR+RZR (8 Weeks) | A3: GT2 NC GZR+UPR+EBR (8 Weeks) | A4: GT2 NC GZR+UPR+RZR (8 Weeks) | A5: GT1 NC GZR+UPR+EBR (8 Weeks) | A6: GT1 NC GZR+UPR+RZR (8 Weeks) | A7: GT2 NC GZR+UPR+EBR (8 Weeks) | A8: GT2 NC GZR+UPR+RZR (8 Weeks) | B9: GT1 NC GZR+UPR+RZR (12 Weeks) | B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV | B11: GT2 NC GZR+UPR+RZR (12 Weeks) | B12: GT1 C GZR+UPR+RZR (8 Weeks) | B13: GT1 C GZR+UPR+RZR (12 Weeks) | B14: GT2 C GZR+UPR+RZR (12 Weeks) | B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV | B16: GT2 C GZR+UPR+RZR (16 Weeks) | B6: GT1 NC GZR+UPR+RVR (8 Weeks) | B8: GT2 NC GZR+UPR+RZR (8 Weeks) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.2 Years STANDARD_DEVIATION 13.5 | 45.0 Years STANDARD_DEVIATION 14.5 | 49.4 Years STANDARD_DEVIATION 15.8 | 52.6 Years STANDARD_DEVIATION 11.6 | 49.0 Years STANDARD_DEVIATION 11.2 | 46.7 Years STANDARD_DEVIATION 13.9 | 52.9 Years STANDARD_DEVIATION 12.1 | 48.3 Years STANDARD_DEVIATION 8.8 | 48.8 Years STANDARD_DEVIATION 13.9 | 49.8 Years STANDARD_DEVIATION 13 | 55.6 Years STANDARD_DEVIATION 14.4 | 58.8 Years STANDARD_DEVIATION 9.6 | 56.9 Years STANDARD_DEVIATION 11.1 | 61.8 Years STANDARD_DEVIATION 6.8 | 59.8 Years STANDARD_DEVIATION 8 | 64.0 Years STANDARD_DEVIATION 9.3 | 47.4 Years STANDARD_DEVIATION 11.7 | 51.4 Years STANDARD_DEVIATION 10.8 | 52.6 Years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 10 Participants | 13 Participants | 7 Participants | 5 Participants | 14 Participants | 9 Participants | 9 Participants | 8 Participants | 21 Participants | 16 Participants | 16 Participants | 14 Participants | 11 Participants | 3 Participants | 4 Participants | 9 Participants | 14 Participants | 9 Participants | 192 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 9 Participants | 9 Participants | 9 Participants | 14 Participants | 6 Participants | 8 Participants | 27 Participants | 15 Participants | 15 Participants | 21 Participants | 29 Participants | 12 Participants | 12 Participants | 17 Participants | 16 Participants | 7 Participants | 250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 23 | 19 / 24 | 10 / 16 | 10 / 14 | 15 / 23 | 13 / 23 | 13 / 15 | 12 / 16 | 18 / 30 | 11 / 16 | 35 / 48 | 24 / 31 | 19 / 31 | 19 / 35 | 26 / 40 | 8 / 15 | 13 / 16 | 14 / 26 |
| serious Total, serious adverse events | 0 / 23 | 1 / 24 | 1 / 16 | 1 / 14 | 0 / 23 | 0 / 23 | 0 / 15 | 0 / 16 | 0 / 30 | 1 / 16 | 0 / 48 | 2 / 31 | 0 / 31 | 1 / 35 | 3 / 40 | 0 / 15 | 0 / 16 | 2 / 26 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)
The percentage of participants with Hepatitis C virus (HCV) ribonucleic acid (RNA) \< Lower Limit of Quantification (LLoQ) 12 weeks after completing treatment (i.e., SVR12) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL.
Time frame: Up to 28 weeks
Population: All randomized participants who received at least 1 dose of study drug and had SVR12 results available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| A2: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| A3: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 68.8 Percentage of Participants |
| A4: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 71.4 Percentage of Participants |
| A5: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| A6: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 91.3 Percentage of Participants |
| B6: GT1 NC GZR+UPR+RVR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| A7: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 60.0 Percentage of Participants |
| A8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 93.8 Percentage of Participants |
| B8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 87.5 Percentage of Participants |
| B9: GT1 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 83.3 Percentage of Participants |
| B11: GT2 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| B12: GT1 C GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 97.1 Percentage of Participants |
| B13: GT1 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| B14: GT2 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
| 16: GT2 C GZR+UPR+RZR (16 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | 100.0 Percentage of Participants |
Primary
Percentage of Participants Discontinuing From Study Treatment Due to an AE
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
Population: All randomized participants who received at least 1 dose of study drug are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| A2: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| A3: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| A4: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| A5: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| A6: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| B6: GT1 NC GZR+UPR+RVR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| A7: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| A8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| B8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| B9: GT1 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 6.5 Percentage of Participants |
| B11: GT2 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| B12: GT1 C GZR+UPR+RZR (8 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| B13: GT1 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 2.5 Percentage of Participants |
| B14: GT2 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
| B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 12.5 Percentage of Participants |
| 16: GT2 C GZR+UPR+RZR (16 Weeks) | Percentage of Participants Discontinuing From Study Treatment Due to an AE | 0 Percentage of Participants |
Primary
Percentage of Participants Experiencing an Adverse Event (AE)
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
Population: All randomized participants who received at least 1 dose of study drug are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 60.9 Percentage of Participants |
| A2: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 83.3 Percentage of Participants |
| A3: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 56.3 Percentage of Participants |
| A4: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 71.4 Percentage of Participants |
| A5: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 73.9 Percentage of Participants |
| A6: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 60.9 Percentage of Participants |
| B6: GT1 NC GZR+UPR+RVR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 62.3 Percentage of Participants |
| A7: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 86.7 Percentage of Participants |
| A8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 75.0 Percentage of Participants |
| B8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 68.8 Percentage of Participants |
| B9: GT1 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 72.9 Percentage of Participants |
| B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV | Percentage of Participants Experiencing an Adverse Event (AE) | 80.6 Percentage of Participants |
| B11: GT2 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 71.0 Percentage of Participants |
| B12: GT1 C GZR+UPR+RZR (8 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 57.1 Percentage of Participants |
| B13: GT1 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 72.5 Percentage of Participants |
| B14: GT2 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 53.3 Percentage of Participants |
| B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV | Percentage of Participants Experiencing an Adverse Event (AE) | 81.3 Percentage of Participants |
| 16: GT2 C GZR+UPR+RZR (16 Weeks) | Percentage of Participants Experiencing an Adverse Event (AE) | 69.2 Percentage of Participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)
The percentage of participants with HCV RNA \< LLoQ 24 weeks after completing treatment (i.e., SVR24) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL.
Time frame: Up to 40 weeks
Population: All randomized participants who received at least 1 dose of study drug and had SVR24 results available are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| A2: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| A3: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 68.8 Percentage of Participants |
| A4: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 71.4 Percentage of Participants |
| A5: GT1 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| A6: GT1 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 90.9 Percentage of Participants |
| B6: GT1 NC GZR+UPR+RVR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| A7: GT2 NC GZR+UPR+EBR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 60.0 Percentage of Participants |
| A8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 93.8 Percentage of Participants |
| B8: GT2 NC GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 87.5 Percentage of Participants |
| B9: GT1 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 83.3 Percentage of Participants |
| B11: GT2 NC GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| B12: GT1 C GZR+UPR+RZR (8 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 97.1 Percentage of Participants |
| B13: GT1 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| B14: GT2 C GZR+UPR+RZR (12 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |
| 16: GT2 C GZR+UPR+RZR (16 Weeks) | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) | 100.0 Percentage of Participants |