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| ID | Type | Description | Link |
|---|---|---|---|
| 142638 | Registry Identifier | JAPIC-CTI |
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This is a two-part study of grazoprevir (MK-5172) + elbasvir (MK-8742) in Japanese participants with chronic hepatitis C virus (HCV) genotype 1 (GT1). Part I is a dose-finding study; in Part II, participants will be randomly assigned to receive grazoprevir at the dose determined in Part I in combination with elbasvir. The primary study hypothesis is that the percentage of treatment-naïve participants in the Immediate Treatment Arm of Part II who achieve sustained viral response at 12 weeks after the end of all treatment (SVR12) will be greater than the reference rate of 75%. A separate study arm for cirrhotic participants will also be included in Part II; these participants will receive grazoprevir at the determined dose in combination with elbasvir.
In Part 1, HCV GT1 participants are randomized into one of two arms: 50 mg grazoprevir plus 50 mg elbasvir for 12 weeks during the double blinded (DB) period followed by 24 weeks of follow-up (FU) during an open-label (OL) period [Arm 1]; or 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks during the DB followed by 24 weeks of FU during the OL [Arm 2]. Unblinding will occur after all participants complete FU Week 4 at which time the grazoprevir dose will be selected.
In Part 2, non-cirrhotic HCV GT1 participants and GT1 participants with compensated liver cirrhosis all receive the selected dose of grazoprevir (50 mg or 100 mg from Part 1) with 50 mg elbasvir for 12 weeks. Non-cirrhotic GT1 participants are randomized to receive either a) 12 weeks of active treatment immediately during the DB with 24 weeks of FU in the OL [Arm 1/Immediate Arm] or b) placebo for 12 weeks with 4 weeks of follow-up during the DB followed by 12 weeks of active treatment and 24 weeks of follow-up during the OL [Arm 2/Deferred Arm]. All cirrhotic participants [Arm 3/Cirrhotic] receive the selected dose immediately for 12 weeks during the DB with 24 weeks of FU during the OL.
Safety analyses for Part 1 and Part 2 arms will focus on the 12 week treatment phase plus the first 4 FU weeks. For the Part 2 Deferred Arm this will include the initial 12 week placebo treatment and first 4 weeks of FU. Efficacy analyses for Parts 1 and 2 will evaluate active treatment only (Weeks 1-12 for all arms except for Part 2 Deferred Arm which is weeks 16-28).
Part 1:
50 mg grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 1) 100 mg grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2)
Part 2:
Selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 1/Immediate) Placebo treatment for 12 weeks, 4 weeks follow-up, selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2/Deferred) Selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 3/Cirrhotic)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Grazoprevir 50 mg + Elbasvir | Experimental | Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir by mouth (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
|
| Part 1 Grazoprevir 100 mg + Elbasvir | Experimental | Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
|
| Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir | Experimental | Non-cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2 and are followed-up for 24 weeks during the open-label period of Part 2. |
|
| Part 2 Non-cirrhotic Deferred: Placeboâ–º Grazoprevir + Elbasvir | Placebo Comparator | Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Grazoprevir | Drug | One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 2: Percentage of Treatment-naïve Participants in the Immediate Treatment Arm Achieving Sustained Viral Response at 12 Weeks After The End of All Treatment (SVR12) | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® Taqman quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, v2.0, which had a lower limit of quantification (LLoQ) of 1.2 Log IU/mL (15 IU/mL) and a lower limit of detection (LLoD) below 15 IU/ml (no specific value). SVR12 was defined as undetectable HCV RNA (target not detected) at 12 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals (CIs) for the SVR12 rate. The lower limit of the 95% CI was compared to the reference rate of 75%; a lower CI limit that was higher than the reference rate would confirm the primary hypothesis and indicate that that the treatment combination was efficacious. As pre-specified in the protocol, only the Immediate Treatment Arm of Part 2 (treatment naïve participants) was included in the primary efficacy analysis. | 12 weeks after end of all therapy in Part 2 (Study Week 24 of Part 2) |
| Part 1: Percentage of Participants Experiencing an Adverse Event (AE) During Treatment and First 4 Follow-Up Weeks | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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, was also an AE. The primary safety evaluation was limited to the initial treatment period through Follow-up Week 4 (FUWK4). | Up to 4 weeks post last dose in Part 1 (Up to total of 16 weeks) |
| Part 1: Percentage of Participants That Discontinued Treatment Due to an AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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, was also an AE. The primary safety evaluation was limited to the initial treatment period through FUWK4. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Percentage of Participants Achieving Undetectable HCV RNA Over Time | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27873094 | Result | Kumada H, Suzuki Y, Karino Y, Chayama K, Kawada N, Okanoue T, Itoh Y, Mochida S, Toyoda H, Yoshiji H, Takaki S, Yatsuzuka N, Yodoya E, Iwasa T, Fujimoto G, Robertson MN, Black S, Caro L, Wahl J. The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study. J Gastroenterol. 2017 Apr;52(4):520-533. doi: 10.1007/s00535-016-1285-y. Epub 2016 Nov 21. |
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Of 432 screened, 63 were enrolled and randomized to Part 1 and 336 were enrolled and randomized to Part 2, for a total of 399 randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 Grazoprevir 50 mg + Elbasvir | Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
| FG001 | Part 1 Grazoprevir 100 mg + Elbasvir | Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
| FG002 | Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir | Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. |
| FG003 | Part 2 Non-cirrhotic Deferred: Placeboâ–º Grazoprevir + Elbasvir | Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2. |
| FG004 | Part 2 Cirrhotic: Grazoprevir + Elbasvir | Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
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| Part 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 Grazoprevir 50 mg + Elbasvir | Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
| BG001 | Part 1 Grazoprevir 100 mg + Elbasvir |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part 2: Percentage of Treatment-naïve Participants in the Immediate Treatment Arm Achieving Sustained Viral Response at 12 Weeks After The End of All Treatment (SVR12) | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® Taqman quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, v2.0, which had a lower limit of quantification (LLoQ) of 1.2 Log IU/mL (15 IU/mL) and a lower limit of detection (LLoD) below 15 IU/ml (no specific value). SVR12 was defined as undetectable HCV RNA (target not detected) at 12 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals (CIs) for the SVR12 rate. The lower limit of the 95% CI was compared to the reference rate of 75%; a lower CI limit that was higher than the reference rate would confirm the primary hypothesis and indicate that that the treatment combination was efficacious. As pre-specified in the protocol, only the Immediate Treatment Arm of Part 2 (treatment naïve participants) was included in the primary efficacy analysis. | The primary efficacy analysis was assessed in all treatment-naïve participants randomized to the Part 2 Immediate Treatment Arm who received ≥1 dose of study treatment and had any follow-up efficacy measurement. No other arms were analyzed for this outcome measure. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 weeks after end of all therapy in Part 2 (Study Week 24 of Part 2) |
Part 1: Up to a total of 36 weeks Part 2: Up to a total of 52 weeks
All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Arm reported separately for placebo and active treatment. Part 1 database=MedDRA 18.1, Part 2 database=MedDRA 19.0
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1 Grazoprevir 50 mg + Elbasvir | Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| C578009 | grazoprevir |
| C000589335 | elbasvir |
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|
| Part 2 Cirrhotic: Grazoprevir + Elbasvir | Experimental | Cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part 1) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. |
|
| Elbasvir | Drug | One 50 mg tablet taken orally once daily for 12 weeks. |
|
| Placebo to Grazoprevir | Drug | One tablet of placebo matched to grazoprevir, taken orally once daily for 12 weeks. |
|
| Placebo to Elbasvir | Drug | One tablet of placebo matched to elbasvir, taken orally once daily for 12 weeks. |
|
| Up to Study Week 12 in Part 1 |
| Part 2: Percentage of Participants Experiencing an AE During Initial Treatment and First 4 Follow-Up Weeks | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo. | Up to 4 weeks following initial treatment in Part 2 (Up to total of 16 weeks) |
| Part 2: Percentage of Participants That Discontinued Initial Treatment Due to an AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo. | Up to Study Week 12 in Part 2 |
| Part 1 Treatment Weeks (TW)2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 |
| Part 1: Percentage of Participants Achieving HCV RNA Below the Lower Limit of Quantitation (<LLoQ) Over Time | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA \ | Part 1 TW2, TW4, TW12, EOT, FUWK4, FUWK12, FUWK24 |
| Part 2: Percentage of Participants Achieving Undetectable HCV RNA Over Time After Active Treatment | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates. | Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 |
| Part 2: Percentage of Participants Achieving HCV RNA <LLoQ Over Time After Active Treatment | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA \ | Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 |
| Started Deferred Active Treatment |
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| COMPLETED |
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| NOT COMPLETED |
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Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
| BG002 | Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir | Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. |
| BG003 | Part 2 Non-cirrhotic Deferred: Placeboâ–º Grazoprevir + Elbasvir | Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2. |
| BG004 | Part 2 Cirrhotic: Grazoprevir + Elbasvir | Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. |
| BG005 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Primary | Part 1: Percentage of Participants Experiencing an Adverse Event (AE) During Treatment and First 4 Follow-Up Weeks | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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, was also an AE. The primary safety evaluation was limited to the initial treatment period through Follow-up Week 4 (FUWK4). | All randomized participants in Part 1 who received ≥1 dose of study treatment and had any safety follow-up data. Data for participants in Part 2 were analyzed and reported separately. | Posted | Number | percentage of participants | Up to 4 weeks post last dose in Part 1 (Up to total of 16 weeks) |
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| Primary | Part 1: Percentage of Participants That Discontinued Treatment Due to an AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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, was also an AE. The primary safety evaluation was limited to the initial treatment period through FUWK4. | All randomized participants in Part 1 who received ≥1 dose of study treatment and had any safety follow-up data. Data for participants in Part 2 were analyzed and reported separately. | Posted | Number | percentage of participants | Up to Study Week 12 in Part 1 |
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|
|
| Secondary | Part 1: Percentage of Participants Achieving Undetectable HCV RNA Over Time | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates. | All randomized participants in Part 1 who have received ≥1 dose of study treatment and who have any follow-up efficacy measurement. Data for participants in Part 2 were analyzed and reported separately. | Posted | Number | 95% Confidence Interval | percentage of participants | Part 1 Treatment Weeks (TW)2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 |
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| Secondary | Part 1: Percentage of Participants Achieving HCV RNA Below the Lower Limit of Quantitation (<LLoQ) Over Time | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA \ | All randomized participants in Part 1 who have received ≥1 dose of study treatment and who have any follow-up efficacy measurement. Data for participants in Part 2 were analyzed and reported separately. | Posted | Number | 95% Confidence Interval | percentage of participants | Part 1 TW2, TW4, TW12, EOT, FUWK4, FUWK12, FUWK24 |
|
|
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| Primary | Part 2: Percentage of Participants Experiencing an AE During Initial Treatment and First 4 Follow-Up Weeks | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo. | All randomized participants in Part 2 who received ≥1 dose of study treatment and had any safety follow-up data. Participants in the Deferred Arm would have received only placebo treatment up to Study Week 16. Data for participants in Part 1 were analyzed and reported separately. | Posted | Number | percentage of participants | Up to 4 weeks following initial treatment in Part 2 (Up to total of 16 weeks) |
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| Primary | Part 2: Percentage of Participants That Discontinued Initial Treatment Due to an AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo. | All randomized participants in Part 2 who received ≥1 dose of study treatment and had any safety follow-up data. Participants in the Deferred Arm would have received only placebo treatment up to Study Week 12. Data for participants in Part 1 were analyzed and reported separately. | Posted | Number | percentage of participants | Up to Study Week 12 in Part 2 |
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| Secondary | Part 2: Percentage of Participants Achieving Undetectable HCV RNA Over Time After Active Treatment | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates. | All randomized participants in Part 2 who have received ≥1 dose of active study treatment and who have any follow-up efficacy measurement. Data for participants in Part 1 were analyzed and reported separately. | Posted | Number | 95% Confidence Interval | percentage of participants | Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 |
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| Secondary | Part 2: Percentage of Participants Achieving HCV RNA <LLoQ Over Time After Active Treatment | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA \ | All randomized participants in Part 2 who have received ≥1 dose of active study treatment and who have any follow-up efficacy measurement. Data for participants in Part 1 were analyzed and reported separately. | Posted | Number | 95% Confidence Interval | percentage of participants | Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24 |
|
|
|
| 2 |
| 31 |
| 16 |
| 31 |
| EG001 | Part 1 Grazoprevir 100 mg + Elbasvir | Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. | 1 | 31 | 17 | 31 |
| EG002 | Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir | Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. | 19 | 227 | 109 | 227 |
| EG003 | Part 2 Non-cirrhotic Deferred: Placebo | Non-cirrhotic participants in the Deferred Treatment Arm take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. | 1 | 74 | 27 | 74 |
| EG004 | Part 2 Non-cirrhotic Deferred: Grazoprevir + Elbasvir | During the open-label period, non-cirrhotic participants in the Deferred Treatment Arm take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks. One participant who received placebo during the blinded period did not receive active treatment during the open-label period. | 2 | 73 | 42 | 73 |
| EG005 | Part 2 Cirrhotic: Grazoprevir + Elbasvir | Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. | 3 | 35 | 27 | 35 |
| Cardiac sarcoidosis | Cardiac disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Colitis ischaemic | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Haemorrhagic erosive gastritis | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Large intestine polyp | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Adenocarcinoma of colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Benign anorectal neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Gastrointestinal tract adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Hepatocellular carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Lead dislodgement | General disorders | MedDRA 18.1 & 19.0 | Systematic Assessment | appears under "Product Issues" in MedDRA v. 19.0 |
|
| Ureterolithiasis | Renal and urinary disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Periodontitis | Infections and infestations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 & 19.0 | Systematic Assessment |
|
The investigator or sub-investigators may publicly present the academic accomplishment acquired from the Study at a specialized academic meeting or research conference. The Sponsor may freely use the information acquired from the Study for the purpose of marketing authorization application of the test drug.
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| TW12 |
|
| EOT |
|
| FUWK4 |
|
| FUWK12 |
|
| FUWK24 |
|
| TW12 |
|
| EOT |
|
| FUWK4 |
|
| FUWK12 |
|
| FUWK24 |
|
|
| TW12 |
|
| EOT |
|
| FUWK4 |
|
| FUWK12 |
|
| FUWK24 |
|
|
| TW12 |
|
| EOT |
|
| FUWK4 |
|
| FUWK12 |
|
| FUWK24 |
|