A Study of Different Doses of Grazoprevir (MK-5172) Given With Pegylated Interferon Alfa-2b and Ribavirin to Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-038)
Study Details
Study Description
Brief Summary
This is a study designed to compare the safety and efficacy of 3 different doses of grazoprevir (MK-5172) combined with pegylated interferon alfa-2b (PEG-IFN) and ribavirin (RBV) in treatment-naïve participants with genotype 1 (GT1) chronic hepatitis C (CHC). Participants will receive 12 weeks of treatment with grazoprevir combined with Peg-IFN and RBV, and depending on response at Week 4 may go on to receive an additional 12 weeks of treatment with Peg-IFN and RBV.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Grazoprevir 25 mg + PEG-IFN + RBV After a maximum of a 45 day screening window, randomized participants receive 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by Response Guided Therapy (RGT). Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their Hepatitis C virus ribonucleic acid (HCV RNA) level at Treatment Week (TW) 4. |
Drug: Grazoprevir
Grazoprevir tablet, orally, once per day at assigned dose
Other Names:
Biological: pegylated interferon alfa-2b
1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection
Other Names:
Drug: Ribavirin
Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight
Other Names:
Drug: Placebo
Placebo to match grazoprevir tablets to maintain dose blinding
|
| Experimental: Grazoprevir 50 mg + PEG-IFN + RBV After a maximum of a 45 day screening window, randomized participants receive 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
Drug: Grazoprevir
Grazoprevir tablet, orally, once per day at assigned dose
Other Names:
Biological: pegylated interferon alfa-2b
1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection
Other Names:
Drug: Ribavirin
Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight
Other Names:
Drug: Placebo
Placebo to match grazoprevir tablets to maintain dose blinding
|
| Experimental: Grazoprevir 100 mg + PEG-IFN + RBV After a maximum of a 45 day screening window, randomized participants receive 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
Drug: Grazoprevir
Grazoprevir tablet, orally, once per day at assigned dose
Other Names:
Biological: pegylated interferon alfa-2b
1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection
Other Names:
Drug: Ribavirin
Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight
Other Names:
Drug: Placebo
Placebo to match grazoprevir tablets to maintain dose blinding
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12) [12 weeks after end of treatment (up to 36 weeks total)]
Hepatitis C virus ribonucleic acid (HCV RNA) was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR12 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 12 weeks after the end of all study therapy.
- Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days [14 days following last dose of study drug (up to 26 weeks)]
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
- Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days [Up to 24 weeks]
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Secondary Outcome Measures
- Percentage of Participants Achieving Undetectable HCV RNA During Treatment by Time Point [From Treatment Week (TW) 2 through end of treatment (up to 24 weeks)]
HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as HCV RNA < 9.3 IU/mL.
- Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment by Time Point [From TW 2 through end of treatment (up to 24 weeks)]
HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.
- Percentage of Participants Achieving SVR4 [4 weeks after end of treatment (up to 28 weeks total)]
HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR4 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 4 weeks after the end of all study therapy.
- Percentage of Subjects Achieving SVR24 [24 weeks after end of treatment (up to 48 weeks total)]
HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR24 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 24 weeks after the end of all study therapy.
- Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response [From Day 1 up to Follow-up Week 24 (up to 48 weeks total)]
Post-baseline resistance associated variants (RAV) analysis was conducted by comparing the amino acid sequences at virologic failure time points to those at baseline (BL): Day 1, pre-dose. A post-BL variant was defined as an amino acid substitution within HCV NS3/4A that was present after the first dose at virologic failure and follow-up visits but not at BL. Post-BL variant analysis was conducted for participants who did not achieve SVR24 who had sequence data available.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Treatment naive
-
Chronic, compensated HCV GT1 infection
-
Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis
-
No evidence of cirrhosis or hepatocellular carcinoma by biopsy or noninvasive testing (e.g. FibroScan and/or FibroTest)
-
Must agree to use two acceptable methods of birth control from at least 2 weeks prior to first dose and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations
Exclusion Criteria:
-
Non-GT1 HCV infection, including a mixed GT infection (with a non-GT1) or a non-typeable genotype.
-
Documented to be Human Immunodeficiency Virus (HIV) positive or co-infected with hepatitis B virus
-
Hepatocellular carcinoma (HCC) or under evaluation for HCC
-
Participating in or has participated in a study with an investigational compound or device within 30 days of signing informed consent
-
Diabetic and/or hypertensive with clinically significant ocular examination findings
-
Current or history of central nervous system trauma, seizure disorder, stroke or transient ischemic attack
-
Chronic pulmonary disease
-
Current or history of any clinically significant cardiac abnormalities/dysfunction
-
Active clinical gout within the last year
-
History of gastric surgery or history of malabsorption disorders
-
Active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin)
-
Pregnant, lactating, expecting to conceive or donate eggs, or male participant planning to impregnate or provide sperm donation or with a female partner who is pregnant
-
Current moderate or severe depression or history of depression associated with hospitalization, electroconvulsive therapy, or severe disruption of daily functions, or suicidal or homicidal ideation and/or attempt, or history of severe psychiatric disorders
-
Evidence or 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.- 5172-038
- 2012-003333-42
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Of 136 screened participants, 87 were randomized to treatment at 19 sites worldwide. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Period Title: Overall Study | |||
| STARTED | 29 | 28 | 30 |
| COMPLETED | 27 | 28 | 30 |
| NOT COMPLETED | 2 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV | Total |
|---|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | Total of all reporting groups |
| Overall Participants | 29 | 28 | 30 | 87 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
52.0
(7.9)
|
48.5
(12.5)
|
46.4
(13.3)
|
48.9
(11.6)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
8
27.6%
|
18
64.3%
|
15
50%
|
41
47.1%
|
| Male |
21
72.4%
|
10
35.7%
|
15
50%
|
46
52.9%
|
Outcome Measures
| Title | Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12) |
|---|---|
| Description | Hepatitis C virus ribonucleic acid (HCV RNA) was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR12 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 12 weeks after the end of all study therapy. |
| Time Frame | 12 weeks after end of treatment (up to 36 weeks total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Per-Protocol (PP) Population (all randomized participants receiving ≥1 dose of study treatment and no important protocol deviation) with available data. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 24 | 25 | 26 |
| Number (95% Confidence Interval) [percentage of participants] |
54.2
186.9%
|
84.0
300%
|
88.5
295%
|
| Title | Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days |
|---|---|
| Description | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. |
| Time Frame | 14 days following last dose of study drug (up to 26 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Participants as Treated (APaT) Population; all randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 29 | 28 | 30 |
| Number [participants] |
28
96.6%
|
28
100%
|
28
93.3%
|
| Title | Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days |
|---|---|
| Description | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| APaT Population; all randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 29 | 28 | 30 |
| Number [participants] |
1
3.4%
|
1
3.6%
|
1
3.3%
|
| Title | Percentage of Participants Achieving Undetectable HCV RNA During Treatment by Time Point |
|---|---|
| Description | HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as HCV RNA < 9.3 IU/mL. |
| Time Frame | From Treatment Week (TW) 2 through end of treatment (up to 24 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PP Population (all randomized participants receiving ≥1 dose of study treatment and no important protocol deviation) with available data. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 29 | 26 | 29 |
| Week 2 (n=29, 25, 29) |
34.5
119%
|
32.0
114.3%
|
55.2
184%
|
| Week 4 (n=28, 26, 29) |
82.1
283.1%
|
76.9
274.6%
|
89.7
299%
|
| Week 12 (n=28, 26, 28) |
96.4
332.4%
|
92.3
329.6%
|
100.0
333.3%
|
| End of All Therapy (n=26, 25, 26) |
92.3
318.3%
|
92.0
328.6%
|
100.0
333.3%
|
| Title | Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment by Time Point |
|---|---|
| Description | HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. |
| Time Frame | From TW 2 through end of treatment (up to 24 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PP Population (all randomized participants receiving ≥1 dose of study treatment and no important protocol deviation) with available data. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 29 | 26 | 29 |
| Week 2 (n=29, 25, 29) |
86.2
297.2%
|
88.0
314.3%
|
96.6
322%
|
| Week 4 (n=28, 26, 29) |
96.4
332.4%
|
100.0
357.1%
|
100.0
333.3%
|
| Week 12 (n=28, 26, 28) |
96.4
332.4%
|
100.0
357.1%
|
100.0
333.3%
|
| End of all Therapy (n=26, 25, 26) |
92.3
318.3%
|
100.0
357.1%
|
100.0
333.3%
|
| Title | Percentage of Participants Achieving SVR4 |
|---|---|
| Description | HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR4 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 4 weeks after the end of all study therapy. |
| Time Frame | 4 weeks after end of treatment (up to 28 weeks total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PP Population (all randomized participants receiving ≥1 dose of study treatment and no important protocol deviation) with available data. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 26 | 25 | 26 |
| Number (95% Confidence Interval) [percentage of participants] |
76.9
265.2%
|
88.0
314.3%
|
92.3
307.7%
|
| Title | Percentage of Subjects Achieving SVR24 |
|---|---|
| Description | HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR24 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 24 weeks after the end of all study therapy. |
| Time Frame | 24 weeks after end of treatment (up to 48 weeks total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PP Population (all randomized participants receiving ≥1 dose of study treatment and no important protocol deviation) with available data. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 24 | 25 | 26 |
| Number (95% Confidence Interval) [percentage of participants] |
54.2
186.9%
|
84.0
300%
|
84.6
282%
|
| Title | Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response |
|---|---|
| Description | Post-baseline resistance associated variants (RAV) analysis was conducted by comparing the amino acid sequences at virologic failure time points to those at baseline (BL): Day 1, pre-dose. A post-BL variant was defined as an amino acid substitution within HCV NS3/4A that was present after the first dose at virologic failure and follow-up visits but not at BL. Post-BL variant analysis was conducted for participants who did not achieve SVR24 who had sequence data available. |
| Time Frame | From Day 1 up to Follow-up Week 24 (up to 48 weeks total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated non-SVR24 participants with BL and post-BL samples sequenced for RAVs. |
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV |
|---|---|---|---|
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Measure Participants | 12 | 7 | 4 |
| Number [participants] |
9
31%
|
5
17.9%
|
3
10%
|
Adverse Events
| Time Frame | From 1st day of treatment (Day 1) through Follow-up Week 24 (up to 48 weeks) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AEs were reported for the APaT Population (all randomized participants who received at least one dose of study treatment) during the treatment period and entire follow-up period. | |||||
| Arm/Group Title | Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV | |||
| Arm/Group Description | After a maximum of a 45 day screening window, randomized participants received 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | After a maximum of a 45 day screening window, randomized participants received 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants could receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. | |||
All Cause Mortality |
||||||
| Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/29 (3.4%) | 2/28 (7.1%) | 0/30 (0%) | |||
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/29 (0%) | 0 | 1/28 (3.6%) | 1 | 0/30 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/29 (0%) | 0 | 1/28 (3.6%) | 1 | 0/30 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholecystitis | 1/29 (3.4%) | 1 | 0/28 (0%) | 0 | 0/30 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Grazoprevir 25 mg + PEG-IFN + RBV | Grazoprevir 50 mg + PEG-IFN + RBV | Grazoprevir 100 mg + PEG-IFN + RBV | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/29 (96.6%) | 28/28 (100%) | 27/30 (90%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 8/29 (27.6%) | 11 | 11/28 (39.3%) | 11 | 11/30 (36.7%) | 11 |
| Leukopenia | 3/29 (10.3%) | 3 | 0/28 (0%) | 0 | 3/30 (10%) | 5 |
| Monocytosis | 1/29 (3.4%) | 1 | 0/28 (0%) | 0 | 3/30 (10%) | 3 |
| Neutropenia | 9/29 (31%) | 9 | 4/28 (14.3%) | 5 | 7/30 (23.3%) | 12 |
| Thrombocytopenia | 2/29 (6.9%) | 2 | 1/28 (3.6%) | 3 | 2/30 (6.7%) | 3 |
| Eye disorders | ||||||
| Eye pain | 1/29 (3.4%) | 1 | 2/28 (7.1%) | 2 | 1/30 (3.3%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 0/29 (0%) | 0 | 0/28 (0%) | 0 | 2/30 (6.7%) | 2 |
| Abdominal pain | 1/29 (3.4%) | 1 | 4/28 (14.3%) | 4 | 1/30 (3.3%) | 1 |
| Aphthous stomatitis | 2/29 (6.9%) | 2 | 0/28 (0%) | 0 | 1/30 (3.3%) | 1 |
| Constipation | 2/29 (6.9%) | 2 | 3/28 (10.7%) | 4 | 3/30 (10%) | 3 |
| Diarrhoea | 2/29 (6.9%) | 2 | 7/28 (25%) | 8 | 5/30 (16.7%) | 5 |
| Dry mouth | 0/29 (0%) | 0 | 3/28 (10.7%) | 3 | 1/30 (3.3%) | 1 |
| Dyspepsia | 1/29 (3.4%) | 1 | 1/28 (3.6%) | 1 | 2/30 (6.7%) | 2 |
| Haemorrhoids | 1/29 (3.4%) | 1 | 3/28 (10.7%) | 4 | 0/30 (0%) | 0 |
| Nausea | 11/29 (37.9%) | 11 | 17/28 (60.7%) | 18 | 9/30 (30%) | 10 |
| Vomiting | 3/29 (10.3%) | 3 | 1/28 (3.6%) | 1 | 6/30 (20%) | 6 |
| General disorders | ||||||
| Asthenia | 2/29 (6.9%) | 2 | 2/28 (7.1%) | 2 | 3/30 (10%) | 3 |
| Chest pain | 2/29 (6.9%) | 2 | 0/28 (0%) | 0 | 0/30 (0%) | 0 |
| Chills | 13/29 (44.8%) | 14 | 12/28 (42.9%) | 12 | 13/30 (43.3%) | 13 |
| Fatigue | 18/29 (62.1%) | 18 | 17/28 (60.7%) | 17 | 18/30 (60%) | 19 |
| Feeling cold | 0/29 (0%) | 0 | 2/28 (7.1%) | 2 | 0/30 (0%) | 0 |
| Influenza like illness | 6/29 (20.7%) | 6 | 7/28 (25%) | 7 | 7/30 (23.3%) | 7 |
| Injection site erythema | 9/29 (31%) | 9 | 8/28 (28.6%) | 8 | 7/30 (23.3%) | 7 |
| Irritability | 8/29 (27.6%) | 8 | 2/28 (7.1%) | 2 | 7/30 (23.3%) | 8 |
| Malaise | 1/29 (3.4%) | 1 | 2/28 (7.1%) | 2 | 0/30 (0%) | 0 |
| Pain | 3/29 (10.3%) | 5 | 2/28 (7.1%) | 2 | 6/30 (20%) | 6 |
| Pyrexia | 10/29 (34.5%) | 12 | 7/28 (25%) | 7 | 11/30 (36.7%) | 11 |
| Infections and infestations | ||||||
| Folliculitis | 2/29 (6.9%) | 2 | 0/28 (0%) | 0 | 0/30 (0%) | 0 |
| Sinusitis | 0/29 (0%) | 0 | 0/28 (0%) | 0 | 2/30 (6.7%) | 4 |
| Urinary tract infection | 2/29 (6.9%) | 2 | 2/28 (7.1%) | 6 | 0/30 (0%) | 0 |
| Vulvovaginal mycotic infection | 0/29 (0%) | 0 | 0/28 (0%) | 0 | 2/30 (6.7%) | 2 |
| Injury, poisoning and procedural complications | ||||||
| Accidental overdose | 4/29 (13.8%) | 4 | 4/28 (14.3%) | 4 | 1/30 (3.3%) | 1 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/29 (3.4%) | 1 | 1/28 (3.6%) | 2 | 3/30 (10%) | 3 |
| Aspartate aminotransferase increased | 1/29 (3.4%) | 1 | 1/28 (3.6%) | 3 | 2/30 (6.7%) | 2 |
| Blood bilirubin increased | 0/29 (0%) | 0 | 2/28 (7.1%) | 4 | 1/30 (3.3%) | 1 |
| Blood creatine phosphokinase increased | 1/29 (3.4%) | 1 | 0/28 (0%) | 0 | 3/30 (10%) | 4 |
| Red cell distribution width increased | 1/29 (3.4%) | 1 | 0/28 (0%) | 0 | 2/30 (6.7%) | 2 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 12/29 (41.4%) | 12 | 7/28 (25%) | 7 | 14/30 (46.7%) | 14 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 5/29 (17.2%) | 6 | 8/28 (28.6%) | 8 | 1/30 (3.3%) | 1 |
| Back pain | 1/29 (3.4%) | 1 | 2/28 (7.1%) | 2 | 4/30 (13.3%) | 5 |
| Muscle spasms | 0/29 (0%) | 0 | 0/28 (0%) | 0 | 3/30 (10%) | 3 |
| Musculoskeletal pain | 0/29 (0%) | 0 | 2/28 (7.1%) | 2 | 3/30 (10%) | 3 |
| Myalgia | 11/29 (37.9%) | 12 | 6/28 (21.4%) | 7 | 9/30 (30%) | 10 |
| Nervous system disorders | ||||||
| Disturbance in attention | 1/29 (3.4%) | 1 | 2/28 (7.1%) | 2 | 1/30 (3.3%) | 1 |
| Dizziness | 6/29 (20.7%) | 7 | 5/28 (17.9%) | 6 | 2/30 (6.7%) | 2 |
| Dysgeusia | 2/29 (6.9%) | 2 | 2/28 (7.1%) | 2 | 4/30 (13.3%) | 4 |
| Headache | 10/29 (34.5%) | 13 | 17/28 (60.7%) | 19 | 13/30 (43.3%) | 17 |
| Lethargy | 0/29 (0%) | 0 | 0/28 (0%) | 0 | 2/30 (6.7%) | 2 |
| Sinus headache | 1/29 (3.4%) | 1 | 0/28 (0%) | 0 | 2/30 (6.7%) | 2 |
| Psychiatric disorders | ||||||
| Anxiety | 1/29 (3.4%) | 1 | 2/28 (7.1%) | 2 | 1/30 (3.3%) | 1 |
| Depression | 3/29 (10.3%) | 3 | 3/28 (10.7%) | 3 | 1/30 (3.3%) | 2 |
| Insomnia | 5/29 (17.2%) | 5 | 3/28 (10.7%) | 3 | 4/30 (13.3%) | 5 |
| Renal and urinary disorders | ||||||
| Chromaturia | 0/29 (0%) | 0 | 2/28 (7.1%) | 2 | 0/30 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 4/29 (13.8%) | 4 | 3/28 (10.7%) | 3 | 5/30 (16.7%) | 6 |
| Dysphonia | 2/29 (6.9%) | 2 | 0/28 (0%) | 0 | 1/30 (3.3%) | 1 |
| Dyspnoea | 5/29 (17.2%) | 5 | 5/28 (17.9%) | 5 | 5/30 (16.7%) | 5 |
| Dyspnoea exertional | 3/29 (10.3%) | 3 | 3/28 (10.7%) | 3 | 4/30 (13.3%) | 4 |
| Oropharyngeal pain | 2/29 (6.9%) | 2 | 1/28 (3.6%) | 2 | 2/30 (6.7%) | 3 |
| Skin and subcutaneous tissue disorders | ||||||
| Dry skin | 2/29 (6.9%) | 2 | 5/28 (17.9%) | 6 | 3/30 (10%) | 3 |
| Pruritus | 5/29 (17.2%) | 5 | 8/28 (28.6%) | 9 | 5/30 (16.7%) | 5 |
| Pruritus generalised | 1/29 (3.4%) | 1 | 0/28 (0%) | 0 | 3/30 (10%) | 3 |
| Rash | 5/29 (17.2%) | 7 | 5/28 (17.9%) | 6 | 4/30 (13.3%) | 5 |
| Rash maculo-papular | 1/29 (3.4%) | 2 | 0/28 (0%) | 0 | 2/30 (6.7%) | 2 |
| Alopecia | 2/29 (6.9%) | 2 | 3/28 (10.7%) | 3 | 3/30 (10%) | 3 |
Limitations/Caveats
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. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
- 5172-038
- 2012-003333-42