Hepatitis C
Conditions
Brief summary
This is a study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12).
Detailed description
The study is an open-label, single-center, multiple-arm investigation of a fixed-dose combination \[FDC\] of grazoprevir 100mg + elbasvir 50mg, and SOF 400mg, in treatment-naive participants with chronic HCV GT1 or GT3. The impact of study treatment regimens of varying duration on SVR12 (undetectable HCV ribonucleic acid \[RNA\] 12 weeks after ending study treatment) in cirrhotic (C) participants and non-cirrhotic (NC) participants will be determined (Part A). Any HCV GT1 participant from study Arms 1-4 in Part A who experienced virologic relapse will be offered retreatment consisting of 12 additional weeks of treatment with MK-5172/MK-8742 + SOF + ribavirin and 24 weeks of follow-up in Part B.
Interventions
DRUGGrazoprevir/Elbasvir FDC
FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.
DRUGSofosbuvir
Sofosbuvir 400mg tablet taken q.d. by mouth.
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
* has HCV RNA ≥10,000 IU/mL in peripheral blood at the time of screening * has documented chronic HCV GT1 or GT3 infection * has either negative or positive history of liver cirrhosis based on liver biopsy, Fibroscan, or FibroSure ® (Fibrotest®) * is treatment naïve to all anti-HCV treatment
Exclusion criteria
* has evidence of decompensated liver disease * is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus * has a history of malignancy ≤5 years prior to signing informed consent, 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 * has any of the following conditions: organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial * has a history of chronic hepatitis not caused by HCV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | Up to 24 weeks | The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) \<15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. |
| Number of Participants Experiencing at Least 1 Adverse Event (AE) | Up to Week 14 | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Discontinuing Study Therapy Due to an AE | Up to Week 12 | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4) | Up to 16 weeks | The percentage of participants achieving SVR4, defined as HCV ribonucleic acid (RNA) \<15 IU/mL 4 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. |
Participant flow
Recruitment details
The current interim disclosure covers data up to 12 weeks after completing study treatment. The cutoff date for this initial disclosure is 12-Feb-2015. GT3 participants have completed treatment but are ongoing in follow-up.
Participants by arm
| Arm | Count |
|---|---|
| GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 4 weeks. | 31 |
| GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks. | 30 |
| GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks. | 20 |
| GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. | 21 |
| GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. | 15 |
| GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. | 14 |
| GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks HCV GT3 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. | 12 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Ongoing in study | 0 | 0 | 0 | 0 | 15 | 14 | 11 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Status not recorded | 4 | 5 | 1 | 4 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | Total | GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks | GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks | GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks | GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks | GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.3 Years STANDARD_DEVIATION 5.3 | 52.3 Years STANDARD_DEVIATION 9.9 | 52.1 Years STANDARD_DEVIATION 9.7 | 51.2 Years STANDARD_DEVIATION 9.5 | 55.7 Years STANDARD_DEVIATION 7.7 | 56.8 Years STANDARD_DEVIATION 8.8 | 51.3 Years STANDARD_DEVIATION 10.1 | 42.2 Years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 2 Participants | 49 Participants | 11 Participants | 11 Participants | 7 Participants | 8 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 10 Participants | 94 Participants | 20 Participants | 19 Participants | 13 Participants | 13 Participants | 11 Participants | 8 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 31 | 2 / 30 | 2 / 20 | 4 / 21 | 4 / 15 | 3 / 14 | 3 / 12 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 | 1 / 20 | 1 / 21 | 1 / 15 | 0 / 14 | 1 / 12 |
Outcome results
Primary
Number of Participants Discontinuing Study Therapy 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 Week 12
Population: The APaT population consists of all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks | Number of Participants Discontinuing Study Therapy Due to an AE | 0 Number of participants |
| GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks | Number of Participants Discontinuing Study Therapy Due to an AE | 0 Number of participants |
| GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks | Number of Participants Discontinuing Study Therapy Due to an AE | 0 Number of participants |
| GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks | Number of Participants Discontinuing Study Therapy Due to an AE | 1 Number of participants |
| GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | Number of Participants Discontinuing Study Therapy Due to an AE | 0 Number of participants |
| GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | Number of Participants Discontinuing Study Therapy Due to an AE | 0 Number of participants |
| GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | Number of Participants Discontinuing Study Therapy Due to an AE | 0 Number of participants |
Primary
Number of Participants Experiencing at Least 1 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 Week 14
Population: The All Participants as Treated (APaT) population consists of all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks | Number of Participants Experiencing at Least 1 Adverse Event (AE) | 5 Number of participants |
| GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks | Number of Participants Experiencing at Least 1 Adverse Event (AE) | 7 Number of participants |
| GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks | Number of Participants Experiencing at Least 1 Adverse Event (AE) | 7 Number of participants |
| GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks | Number of Participants Experiencing at Least 1 Adverse Event (AE) | 4 Number of participants |
| GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | Number of Participants Experiencing at Least 1 Adverse Event (AE) | 4 Number of participants |
| GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | Number of Participants Experiencing at Least 1 Adverse Event (AE) | 3 Number of participants |
| GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | Number of Participants Experiencing at Least 1 Adverse Event (AE) | 3 Number of participants |
Primary
Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12)
The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) \<15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.
Time frame: Up to 24 weeks
Population: The Per Protocol (PP) population includes all randomized and treated participants who did not have protocol deviations that may substantially affect the results of the primary and secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | 33.3 Percentage of participants |
| GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | 89.3 Percentage of participants |
| GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | 80.0 Percentage of participants |
| GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | 89.5 Percentage of participants |
| GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | 93.3 Percentage of participants |
| GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | 100.0 Percentage of participants |
| GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | 90.9 Percentage of participants |
Secondary
Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4)
The percentage of participants achieving SVR4, defined as HCV ribonucleic acid (RNA) \<15 IU/mL 4 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.
Time frame: Up to 16 weeks
Population: Analysis of SVR4 is ongoing and results will be indicated in a future report.