Hepatitis C Virus
Conditions
Brief summary
In this study, participants with hepatitis C virus (HCV) genotype 1 (GT1) who failed prior direct-acting antiviral (DAA) therapy will receive Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) to evaluate sustained virologic response (SVR) using this drug combination.
Interventions
DRUGGrazoprevir (GZR)
100 mg oral tablet (total daily dose)
DRUGElbasvir (EBR)
10 mg oral capsule (total daily dose = 5 capsules)
DRUGRibavirin (RBV)
200 mg oral capsule (total daily dose = 4-7 capsules)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented chronic HCV GT1 infection (with no evidence of non-typable or mixed genotype) * Absence of cirrhosis, or cirrhosis with these criteria: METAVIR F4, or Fibroscan with result \>12.5 kPa, or FibroSure® (Fibrotest®) score of \>0.75 + aspartate aminotransferase (AST): platelet ratio index (APRI) of \>2- Prior regimen containing an approved DAA (boceprevir, telaprevir, simeprevir, or sofosbuvir), pegylated interferon, and/or RBV * Participants of reproductive potential must agree to remain truly abstinent or use (or have their partner use) 2 acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations
Exclusion criteria
* Received any HCV regimen containing a DAA with the exception of boceprevir, telaprevir, simeprevir, or sofosbuvir in combination with pegylated interferon and/or RBV * Evidence of decompensated liver disease or cirrhosis * Co-infected with hepatitis B virus or human immunodeficiency virus (HIV) * 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 under evaluation for other active or suspected malignancy * Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC * Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study * Clinically-relevant drug or alcohol abuse within 12 months of screening * Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations * Male participant whose female partner (s) is/are pregnant * Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair * Poor venous access * History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease) * Hemoglobinopathy, including, but not limited to, thalassemia major * Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial * Evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12) | Up to 24 weeks | SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, \<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. |
| Percentage of Participants Experiencing Adverse Events | Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug) | Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. |
| Percentage of Participants Discontinuing Study Drug Due to an Adverse Event | Up to 12 weeks | Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy | Up to 24 weeks | SVR12 is defined as participants having HCV RNA level lower than the LLoQ (\<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with our without resistance-associated variants (RAVs) of the hepatitis C virus. |
Participant flow
Pre-assignment details
Following 12 weeks of treatment with grazoprevir (GZR), elbasvir (EBR) and ribavirin (RBV), participants were followed-up for an additional 24 weeks.
Participants by arm
| Arm | Count |
|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | GZR 100 mg + EBR 50 mg + RBV for 12 Weeks |
|---|---|
| Age, Continuous | 54.4 Years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 79 |
| serious Total, serious adverse events | 6 / 79 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12)
SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, \<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.
Time frame: Up to 24 weeks
Population: Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12) | 97.1 Percentage of participants |
Primary
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
Time frame: Up to 12 weeks
Population: All participants as treated population defined as all participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Discontinuing Study Drug Due to an Adverse Event | 1.3 Percentage of participants |
Primary
Percentage of Participants Experiencing Adverse Events
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
Time frame: Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)
Population: All participants as treated population defined as all participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Experiencing Adverse Events | 79.7 Percentage of participants |
Secondary
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
SVR12 is defined as participants having HCV RNA level lower than the LLoQ (\<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with our without resistance-associated variants (RAVs) of the hepatitis C virus.
Time frame: Up to 24 weeks
Population: Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy | Boceprevir with signature baseline RAVs, n=9 | 88.9 Percentage of participants |
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy | Boceprevir without signature baseline RAVs, n=16 | 100.0 Percentage of participants |
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy | Telaprevir with signature baseline RAVs, n=18 | 94.4 Percentage of participants |
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy | Telaprevir without signature baseline RAVs, n=22 | 100.0 Percentage of participants |
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy | Simeprevir with signature baseline RAVs, n=4 | 100.0 Percentage of participants |
| GZR 100 mg + EBR 50 mg + RBV for 12 Weeks | Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy | Simeprevir without signature baseline RAVs, n=1 | 100.0 Percentage of participants |