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This is a study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12).
The study is an open-label, single-center, multiple-arm investigation of a fixed-dose combination [FDC] of grazoprevir 100mg + elbasvir 50mg, and SOF 400mg, in treatment-naive participants with chronic HCV GT1 or GT3. The impact of study treatment regimens of varying duration on SVR12 (undetectable HCV ribonucleic acid [RNA] 12 weeks after ending study treatment) in cirrhotic (C) participants and non-cirrhotic (NC) participants will be determined (Part A). Any HCV GT1 participant from study Arms 1-4 in Part A who experienced virologic relapse will be offered retreatment consisting of 12 additional weeks of treatment with MK-5172/MK-8742 + SOF + ribavirin and 24 weeks of follow-up in Part B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GT1:NC Grazoprevir/Elbasvir+SOF 4wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned). |
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| GT1:NC Grazoprevir/Elbasvir+SOF 6wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned). |
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| GT1:C Grazoprevir/Elbasvir+SOF 6wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned). |
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| GT1:C Grazoprevir/Elbasvir+SOF 8wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned). |
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| GT3:NC Grazoprevir/Elbasvir+SOF 8wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Grazoprevir/Elbasvir FDC | Drug | FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) <15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. | Up to 24 weeks |
| Number of Participants Experiencing at Least 1 Adverse Event (AE) | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to Week 14 |
| Number of Participants Discontinuing Study Therapy Due to an AE | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4) | The percentage of participants achieving SVR4, defined as HCV ribonucleic acid (RNA) <15 IU/mL 4 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. | Up to 16 weeks |
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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 |
|---|---|---|---|
| 27770561 | Result | Lawitz E, Poordad F, Gutierrez JA, Wells JT, Landaverde CE, Evans B, Howe A, Huang HC, Li JJ, Hwang P, Dutko FJ, Robertson M, Wahl J, Barr E, Haber B. Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial. Hepatology. 2017 Feb;65(2):439-450. doi: 10.1002/hep.28877. Epub 2016 Dec 19. |
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The current interim disclosure covers data up to 12 weeks after completing study treatment. The cutoff date for this initial disclosure is 12-Feb-2015. GT3 participants have completed treatment but are ongoing in follow-up.
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| ID | Title | Description |
|---|---|---|
| FG000 | GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks | HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 4 weeks. |
| FG001 | GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| GT3:NC Grazoprevir/Elbasvir+SOF 12wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned). |
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| GT3:C Grazoprevir/Elbasvir+SOF 12wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned). |
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| Sofosbuvir | Drug | Sofosbuvir 400mg tablet taken q.d. by mouth. |
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HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks.
| FG002 | GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks | HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks. |
| FG003 | GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. |
| FG004 | GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. |
| FG005 | GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
| FG006 | GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks | HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 4 weeks. |
| BG001 | GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks | HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks. |
| BG002 | GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks | HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks. |
| BG003 | GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. |
| BG004 | GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. |
| BG005 | GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
| BG006 | GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| 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 | Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) <15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. | The Per Protocol (PP) population includes all randomized and treated participants who did not have protocol deviations that may substantially affect the results of the primary and secondary endpoints. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to 24 weeks |
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| Primary | Number of Participants Experiencing at Least 1 Adverse Event (AE) | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | The All Participants as Treated (APaT) population consists of all participants who received ≥1 dose of study drug. | Posted | Number | Number of participants | Up to Week 14 |
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| Primary | Number of Participants Discontinuing Study Therapy Due to an AE | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | The APaT population consists of all participants who received ≥1 dose of study drug. | Posted | Number | Number of participants | Up to Week 12 |
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| Secondary | Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4) | The percentage of participants achieving SVR4, defined as HCV ribonucleic acid (RNA) <15 IU/mL 4 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. | Analysis of SVR4 is ongoing and results will be indicated in a future report. | Posted | Up to 16 weeks |
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Up to 14 weeks
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
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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 | GT1: NC Grazoprevir/Elbasvir + SOF 4 Weeks | HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 4 weeks. | 0 | 31 | 2 | 31 | ||
| EG001 | GT1: NC Grazoprevir/Elbasvir + SOF 6 Weeks | HCV GT1 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks. | 0 | 30 | 2 | 30 | ||
| EG002 | GT1: C Grazoprevir/Elbasvir + SOF 6 Weeks | HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 6 weeks. | 1 | 20 | 2 | 20 | ||
| EG003 | GT1: C Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. | 1 | 21 | 4 | 21 | ||
| EG004 | GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. | 1 | 15 | 4 | 15 | ||
| EG005 | GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. | 0 | 14 | 3 | 14 | ||
| EG006 | GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. | 1 | 12 | 3 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemorrhagic anaemia | Blood and lymphatic system disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Hepatic mass | Hepatobiliary disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Lobar pneumonia | Infections and infestations | MedDRA v. 16.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA v. 16.0 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA v. 16.0 | Systematic Assessment |
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| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v. 16.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA v. 16.0 | Systematic Assessment |
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| Accidental overdose | Injury, poisoning and procedural complications | MedDRA v. 16.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA v. 16.0 | Systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | MedDRA v. 16.0 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialDisclosure@merck.com |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C578009 | grazoprevir |
| C000611265 | elbasvir-grazoprevir drug combination |
| D000069474 | Sofosbuvir |
| ID | Term |
|---|---|
| D014542 | Uridine Monophosphate |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |
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| Male |
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HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks.
| OG004 | GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. |
| OG005 | GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
| OG006 | GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
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| OG004 | GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. |
| OG005 | GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
| OG006 | GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
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HCV GT1 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks.
| OG004 | GT3: NC Grazoprevir/Elbasvir + SOF 8 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 8 weeks. |
| OG005 | GT3: NC Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 NC participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
| OG006 | GT3: C Grazoprevir/Elbasvir + SOF 12 Weeks | HCV GT3 C participants took grazoprevir 100 mg + elbasvir 50 mg FDC with SOF 400 mg for 12 weeks. |
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