Hepatitis C
Conditions
Brief summary
This is a randomized, multi-site, placebo-controlled trial of a fixed dose combination (FDC) of grazoprevir (MK-5172) 100 mg + elbasvir (MK-8742) 50 mg in participants with chronic Hepatitis C Virus (HCV) genotype (GT) 1, GT4 or GT6 with inherited blood disorders. The primary hypothesis is that the proportion of participants treated with grazoprevir+elbasvir achieving Sustained Virologic Response (SVR) 12 weeks after the end of all study therapy (SVR12) will be greater than the reference rate of 40%.
Interventions
FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth.
DRUGPlacebo
Placebo tablets matching grazoprevir + elbasvir FDC tablets taken once daily by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* has HCV GT1, GT4, or GT6 with sickle cell anemia, thalassemia, or hemophilia/von Willebrand disease * has cirrhosis or is non-cirrhotic * is human immunodeficiency virus (HIV) coinfected or not infected with HIV * is a female of non childbearing potential, or is male or female and uses an acceptable method(s) of contraception
Exclusion criteria
* has evidence of decompensated liver disease * is coinfected with hepatitis B * has had a malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer * has hepatocellular carcinoma (HCC) or is under evaluation for HCC * has clinically-relevant drug or alcohol abuse within 12 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) | 12 weeks after completing study therapy (Week 24) | The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid \[RNA\] level below the lower limit of quantification \[LLoQ\] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL. |
| Percentage of Participants Experiencing an Adverse Event (AE) | Up to Week 14 | An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. |
| Percentage of Participants Discontinuing From Study Treatment Due to an AE(s) | Up to Week 12 | An AE is any untoward medical occurrence 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 Completing Study Therapy (SVR24) | 24 weeks after completing study therapy (Week 36) | The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL. |
Participant flow
Recruitment details
Adult participants with hepatitis C virus (HCV) genotypes (GT)1, GT4, and GT6 with inherited blood disorders and with or without human immunodeficiency virus (HIV) co-infection were recruited at study centers around the world.
Participants by arm
| Arm | Count |
|---|---|
| Immediate Treatment Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period. | 107 |
| Deferred Treatment Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period. | 52 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Immediate Treatment | Deferred Treatment | Total |
|---|---|---|---|
| Age, Continuous | 44.2 Years STANDARD_DEVIATION 11.2 | 42.5 Years STANDARD_DEVIATION 9.8 | 43.6 Years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 27 Participants | 13 Participants | 40 Participants |
| Sex: Female, Male Male | 80 Participants | 39 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 78 / 107 | 34 / 52 |
| serious Total, serious adverse events | 6 / 107 | 6 / 52 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid \[RNA\] level below the lower limit of quantification \[LLoQ\] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL.
Time frame: 12 weeks after completing study therapy (Week 24)
Population: The Full Analysis Set (FAS) consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Treatment | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) | 93.5 Percentage of participants |
| Deferred Treatment | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) | 91.8 Percentage of participants |
Primary
Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)
An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to Week 12
Population: The APaT population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Treatment | Percentage of Participants Discontinuing From Study Treatment Due to an AE(s) | 0.0 Percentage of Participants |
| Deferred Treatment | Percentage of Participants Discontinuing From Study Treatment Due to an AE(s) | 1.9 Percentage of Participants |
Comparison: The estimated difference (± 95% CI) in percentage of participants withdrawing from study treatment due to an AE(s) in the Immediate versus Deferred arms was determined.p-value: 0.15595% CI: [-10.2, 1.6]Miettinen & Nurminen method
Primary
Percentage of Participants Experiencing an Adverse Event (AE)
An AE is any untoward medical occurrence 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 includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Treatment | Percentage of Participants Experiencing an Adverse Event (AE) | 72.9 Percentage of Participants |
| Deferred Treatment | Percentage of Participants Experiencing an Adverse Event (AE) | 65.4 Percentage of Participants |
Comparison: The estimated difference (± 95% confidence interval \[CI\]) in percentage of participants experiencing an AE in the Immediate versus Deferred arms was determined.95% CI: [-7.3, 23.3]
Secondary
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)
The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL.
Time frame: 24 weeks after completing study therapy (Week 36)
Population: The FAS consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Treatment | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24) | 90.7 Percentage of participants |
| Deferred Treatment | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24) | 91.8 Percentage of participants |