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| ID | Type | Description | Link |
|---|---|---|---|
| TMC435HPC2013 | Other Identifier | Janssen Research & Development, LLC |
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The purpose of this study is to evaluate the efficacy of 6 or 8 weeks of treatment regimen containing simeprevir (SMV), daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive (not having received treatment with any approved or investigational drug) participants with chronic hepatitis (inflammation of the liver) C virus (HCV) genotype 1 infection with early stages of liver fibrosis or with cirrhosis.
This is an open-label (participants and researchers are aware about the treatment participants are receiving), and multicenter (when more than 1 hospital or medical school team work on a medical research) study. The study will consist of a Screening Phase (6 weeks); an Open-label Treatment Phase (6 weeks for Arm A and 8 weeks for Arm B); and a Post-treatment Follow-up Phase (until 24 weeks after end of study treatment). Using a staggered approach, all eligible participants will be assigned to 1 of the 2 arms, according to their level of fibrosis. Arm A (consists of chronic HCV genotype 1 infected participants with early stages of liver fibrosis): participants will receive a combination therapy of SMV 150 milligram (mg), DCV 60 mg and SOF 400 mg once daily for 6 weeks. Arm B (consists of chronic HCV genotype 1 infected participants with cirrhosis): participants will receive a combination therapy of SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks. A sub-study will be performed at a selected study site, where only participants who will be eligible to participate in both the main study and the sub-study will be enrolled. Intra-hepatic and plasma HCV ribonucleic acid (RNA) levels; intra-hepatic, peripheral innate and adaptive immune responses during the treatment, will be assessed in the sub-study. Participants' safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis, will receive Simeprevir (SMV) 150 milligram (mg), Daclatasvir (DCV) 60 mg and Sofosbuvir (SOF) 400 mg once daily for 6 weeks. |
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| Arm B | Experimental | Chronic HCV genotype 1 infected participants with cirrhosis, will receive SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simeprevir 150 mg | Drug | Simeprevir 150 mg capsule orally once daily. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12) | Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the end of study drug treatment. | 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Response | On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold. The following thresholds were considered at any time point: \ |
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Inclusion Criteria:
Exclusion Criteria:
A. Main Study:
B. Sub-study:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bakersfield | California | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29274193 | Derived | Sulkowski MS, Feld JJ, Lawitz E, Felizarta F, Corregidor AM, Khalid O, Ghalib R, Smith WB, Van Eygen V, Luo D, Vijgen L, Gamil M, Kakuda TN, Ouwerkerk-Mahadevan S, Van Remoortere P, Beumont M. Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection. J Viral Hepat. 2018 Jun;25(6):631-639. doi: 10.1111/jvh.12853. Epub 2018 Feb 6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis received therapy (Simeprevir [SMV] 150 milligram (mg)/Daclatasvir [DCV] 60mg/Sofosbuvir [SOF] 400mg) once daily for 6 weeks. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Daclatasvir 60 mg |
| Drug |
Daclatasvir 60 mg tablet orally once daily. |
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| Sofosbuvir 400 mg | Drug | Sofosbuvir 400 mg tablet orally once daily. |
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| Day 2, Day 3, Week 1, 2, 3, 4, 6 (for Arm A) and 8 (for Arm B only) |
| Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment | Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was \ | 4 weeks after end of study drug treatment (week 10 for Arm A and 12 for Arm B); 24 weeks after end of study drug treatment (week 30 for Arm A and 32 for Arm B) |
| Percentage of Participants With On-Treatment Failure | Participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. Includes participants with: 1) viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA 2) confirmed detectable HCV RNA at the actual end of treatment (example, completed treatment, discontinued due to adverse events, withdrawal of consent) of >100 IU/mL in participants whose HCV RNA had previously been \ | Baseline up to End of Treatment (Week 6 for Arm A and Week 8 for Arm B) |
| Number of Participants With Viral Relapse | Viral Relapse: Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during followup. | From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B) |
| Number of Participants With Late Viral Relapse | Late Viral Relapse: Participant who achieved SVR12 and the post treatment HCV RNA measurement fulfilled 1 the following conditions: a) at least 2 consecutive measurements not lesser than (<)15 IU/mL undetectable, of which at least the second measurement was >=15 IU/mL quantifiable or b) the last available measurement was >=15 IU/mL quantifiable. | From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B) |
| Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR | Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify preexisting sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. | Up to Week 30 for Arm A and up to Week 32 for Arm B |
| Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR | The Q80K polymorphism, associated with low level SMV in vitro resistance. Percentage of participants who achieved SVR with or without an NS3 Q80K polymorphism at baseline were reported. | up to Week 30 for Arm A and Week 32 for Arm B |
| Jacksonville |
| Florida |
| United States |
| Lutherville | Maryland | United States |
| Winston-Salem | North Carolina | United States |
| Knoxville | Tennessee | United States |
| Arlington | Texas | United States |
| San Antonio | Texas | United States |
| Toronto | Ontario | Canada |
| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks |
Chronic hepatitis C virus (HCV) genotype 1 infected participants with compensated cirrhosis received therapy (Simeprevir [SMV] 150 milligram (mg)/Daclatasvir [DCV] 60mg/Sofosbuvir [SOF] 400mg) once daily for 8 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis received therapy (Simeprevir [SMV] 150 milligram (mg)/Daclatasvir [DCV] 60mg/Sofosbuvir [SOF] 400mg) once daily for 6 weeks. |
| BG001 | Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | Chronic hepatitis C virus (HCV) genotype 1 infected participants with compensated cirrhosis received therapy (Simeprevir [SMV] 150 milligram (mg)/Daclatasvir [DCV] 60mg/Sofosbuvir [SOF] 400mg) once daily for 8 weeks. |
| BG002 | 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 | Median | Full Range | years |
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| Gender | Count of Participants | Participants |
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| Region of Enrollment | Number | 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 Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12) | Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the end of study drug treatment. | The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV). | Posted | Number | Percentage of Participants | 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B) |
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| Secondary | Percentage of Participants With On-treatment Virologic Response | On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold. The following thresholds were considered at any time point: \ | The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV). Here 'n' signifies number of participants who were evaluable at each specified time point, for each arm, respectively. | Posted | Number | Percentage of Participants | Day 2, Day 3, Week 1, 2, 3, 4, 6 (for Arm A) and 8 (for Arm B only) |
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| Secondary | Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment | Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was \ | The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV). | Posted | Number | Percentage of Participants | 4 weeks after end of study drug treatment (week 10 for Arm A and 12 for Arm B); 24 weeks after end of study drug treatment (week 30 for Arm A and 32 for Arm B) |
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| Secondary | Percentage of Participants With On-Treatment Failure | Participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. Includes participants with: 1) viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA 2) confirmed detectable HCV RNA at the actual end of treatment (example, completed treatment, discontinued due to adverse events, withdrawal of consent) of >100 IU/mL in participants whose HCV RNA had previously been \ | The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV). | Posted | Number | Percentage of Participants | Baseline up to End of Treatment (Week 6 for Arm A and Week 8 for Arm B) |
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| Secondary | Number of Participants With Viral Relapse | Viral Relapse: Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during followup. | The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV). | Posted | Number | Participants | From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B) |
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| Secondary | Number of Participants With Late Viral Relapse | Late Viral Relapse: Participant who achieved SVR12 and the post treatment HCV RNA measurement fulfilled 1 the following conditions: a) at least 2 consecutive measurements not lesser than (<)15 IU/mL undetectable, of which at least the second measurement was >=15 IU/mL quantifiable or b) the last available measurement was >=15 IU/mL quantifiable. | The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV). | Posted | Number | Participants | From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B) |
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| Secondary | Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR | Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify preexisting sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. | The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV). | Posted | Number | Participants | Up to Week 30 for Arm A and up to Week 32 for Arm B |
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| Secondary | Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR | The Q80K polymorphism, associated with low level SMV in vitro resistance. Percentage of participants who achieved SVR with or without an NS3 Q80K polymorphism at baseline were reported. | The ITT analysis set is defined as all enrolled participants who took at least 1 dose of SMV, SOF or DCV. Here, N (number of participants analyzed) signifies participants who were evaluable for this outcome measure and 'n' signifies number of participants evaluable for this outcome measure at specific time point. | Posted | Number | Percentage of Participants | up to Week 30 for Arm A and Week 32 for Arm B |
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Only adverse events from the Treatment Period (6 weeks in Arm A and 8 weeks in Arm B) are reported.
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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 | Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis received therapy (Simeprevir [SMV] 150 milligram (mg)/Daclatasvir [DCV] 60mg/Sofosbuvir [SOF] 400mg) once daily for 6 weeks. | 1 | 59 | 39 | 59 | ||
| EG001 | Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | Chronic hepatitis C virus (HCV) genotype 1 infected participants with compensated cirrhosis received therapy (Simeprevir [SMV] 150 milligram (mg)/Daclatasvir [DCV] 60mg/Sofosbuvir [SOF] 400mg) once daily for 8 weeks. | 0 | 9 | 4 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest Pain | General disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA Version 17.1 | Non-systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 17.1 | Non-systematic Assessment |
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| Procedural Pain | Injury, poisoning and procedural complications | MedDRA Version 17.1 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Photosensitivity Reaction | Skin and subcutaneous tissue disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Pruritus Generalised | Skin and subcutaneous tissue disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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The sample size in Arm B (participants with cirrhosis) was small (n=9).
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Associate Director, Medical Department | Janssen R&D BE | ClinicalTrialDisclosure@its.jnj.com |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| D008103 | Liver Cirrhosis |
| D005355 | Fibrosis |
| 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 |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069616 | Simeprevir |
| C549273 | daclatasvir |
| D000069474 | Sofosbuvir |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D014542 | Uridine Monophosphate |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |
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| USA |
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