Back to resultsAn Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease
Primary Purpose
Hepatitis C, Chronic
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Simeprevir
Daclatasvir
Sofosbuvir
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Hepatitis C, Chronic, Simeprevir, Daclatasvir, Sofosbuvir, Decompensated Liver Disease
Eligibility Criteria
Inclusion Criteria:
- Documented chronic Hepatitis C virus (HCV) infection: diagnosis of HCV more than (>) 6 months before the Screening visit, either by detectable HCV ribonucleic acid (RNA), a HCV positive antibody or the presence of histological changes consistent with chronic hepatitis
- HCV genotype 1 or 4 infection and HCV RNA plasma level >10,000 international unit per milliliter (IU/mL) (both determined at screening)
- Presence of cirrhosis, which is defined as a FibroScan with a result of >14.5 kilopascals (kPa) at Screening
- HCV treatment-naive participants: participant has not received treatment with any approved or investigational drug for the treatment of HCV infection and HCV treatment-experienced participants: participant has had at least 1 documented previous course of a non-direct-acting antiviral agent (DAA), interferon (IFN)-based HCV therapy (with or without Ribavirin [RBV]). Last dose in this previous course should have occurred at least 2 months prior to Screening
- Decompensated liver disease: Panel 1: Child Pugh A (mild hepatic impairment) with evidence of portal hypertension [confirmed by the presence of esophageal varices on gastroscopy or hepatic venous pressure gradient (HVPG) greater than or equal to (>=) 10 millimeter of mercury (mm Hg)], Panel 2: Child-Pugh B (moderate hepatic impairment) 7 to 9 (extremes included)
Exclusion Criteria:
- Co-infection with any HCV genotype
- Co-infection with human immunodeficiency virus (HIV)-1 or -2 (positive HIV-1 or HIV-2 antibodies test at Screening)
- Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
- Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the Investigator
- Use of any disallowed therapies before the planned first dose of study drugs
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Panel 1
Panel 2
Arm Description
Participants with Child-Pugh score <7 with evidence of portal hypertension (confirmed by presence of esophageal varices or hepatic venous pressure gradient [HVPG] greater than or equal to 10 millimeter of mercury [mm Hg]) will receive simeprevir (150 milligram [mg] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.
Participants with Child-Pugh score 7 to 9 (extremes included) will receive simeprevir (150 mg capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Sustained Virologic Response 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.
Secondary Outcome Measures
Percentage of Participants With On-Treatment Virologic Response
On-treatment virologic response was determined by HCV RNA results satisfying a specified threshold. The following thresholds were considered at any time point: <LLOQ undetectable, <LLOQ detectable, and <LLOQ undetectable or detectable. The LLOQ value was 15 IU/mL. Very rapid virologic response (vRVR) is undetectable HCV RNA at Week 2 while on treatment and Rapid virologic response (RVR) is undetectable HCV RNA at Week 4 while on treatment.
Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24)
Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was <LLOQ detectable or undetectable at 4 weeks and 24 weeks respectively after the end of study drug treatment. The LLOQ value was 15 IU/mL.
Percentage of Participants With HCV NS3/4A Sequence, NS5A and NS5B After End of Treatment 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 pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. All participants in this study achieved SVR12. Therefore, reasons for not achieving SVR12 are not applicable.
Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36)
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
Tmax is the time to reach maximum observed plasma concentration.
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after dosing.
Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The Cmax is the maximum observed plasma concentration.
Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The Cmin is the minimum observed plasma concentration.
Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
The C0h is the pre-dose plasma concentration.
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment.
Percentage of Participants With Viral Relapse
Viral relapse is defined as participants who do 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 (15 IU/mL) at Week 16, 24 or 36.
Percentage of Participants With SVR12 Who Maintained to Have HCV RNA <LLOQ Until the End of 3 Years Follow up
Percentage of participants with SVR12 who maintained to have HCV RNA <LLOQ (15 IU/mL) until the end of 3 years follow up were reported.
Full Information
NCT ID
NCT02262728
First Posted
October 6, 2014
Last Updated
April 24, 2019
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02262728
Brief Title
An Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease
Official Title
A Phase 2 Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of 12 Weeks of Treatment With Simeprevir, Daclatasvir and Sofosbuvir, Followed by a 5-Year Post-treatment Long-term Follow-up, in Treatment-naïve and Treatment-experienced Subjects With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
September 30, 2014 (Actual)
Primary Completion Date
August 13, 2015 (Actual)
Study Completion Date
April 25, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy of a 12-week regimen containing simeprevir, daclatasvir and sofosbuvir in participants with decompensated liver disease (the liver function is insufficient) due to genotype 1 or 4 Hepatitis (inflammation of the liver) C virus (HCV) infection by assessing sustained virologic response 12-weeks after the end of study drug treatment (SVR12).
Detailed Description
This is an open-label (all people know which treatment the participants receive) Phase 2 study to investigate the efficacy, safety and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir in treatment-naive (participants have never received HCV treatment with any approved or investigational agent) and treatment - experienced (participants have failed at least one previous course of [Pegylated] interferon [(Peg)IFN], with or without Ribavirin) participants. Participants will be assigned to 1 of 2 panels: Panel 1 (n=20): Child-Pugh score less than (<) 7 with evidence of portal hypertension (confirmed by presence of esophageal varices or HVPG greater than or equal to [>=] 10 mm Hg); Panel 2 (n=20): Child-Pugh score 7 to 9 (extremes included). The total study duration for each participant will be approximately 276 weeks. The study will consist of 3 parts: Screening Phase (approximately 4 weeks) and open-label treatment Phase (from Week 4 to 16) and follow-up Phase (until 5 years after the actual end of study drug treatment). Participants will receive simeprevir (150 milligram [mg] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks. Efficacy will be primarily evaluated by percentage of participants with SVR12. Participants' safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
Keywords
Hepatitis C, Chronic, Simeprevir, Daclatasvir, Sofosbuvir, Decompensated Liver Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panel 1
Arm Type
Experimental
Arm Description
Participants with Child-Pugh score <7 with evidence of portal hypertension (confirmed by presence of esophageal varices or hepatic venous pressure gradient [HVPG] greater than or equal to 10 millimeter of mercury [mm Hg]) will receive simeprevir (150 milligram [mg] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.
Arm Title
Panel 2
Arm Type
Experimental
Arm Description
Participants with Child-Pugh score 7 to 9 (extremes included) will receive simeprevir (150 mg capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Simeprevir
Other Intervention Name(s)
TMC435
Intervention Description
Simeprevir 150 milligram (mg) capsule orally once daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Daclatasvir
Other Intervention Name(s)
BMS-790052
Intervention Description
Daclatasvir 60 mg tablet orally once daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir
Other Intervention Name(s)
GS-7977
Intervention Description
Sofosbuvir 400 mg tablet orally once daily for 12 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With On-Treatment Virologic Response
Description
On-treatment virologic response was determined by HCV RNA results satisfying a specified threshold. The following thresholds were considered at any time point: <LLOQ undetectable, <LLOQ detectable, and <LLOQ undetectable or detectable. The LLOQ value was 15 IU/mL. Very rapid virologic response (vRVR) is undetectable HCV RNA at Week 2 while on treatment and Rapid virologic response (RVR) is undetectable HCV RNA at Week 4 while on treatment.
Time Frame
Week 1, 2, 4, 6, 8, 10, 12
Title
Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24)
Description
Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was <LLOQ detectable or undetectable at 4 weeks and 24 weeks respectively after the end of study drug treatment. The LLOQ value was 15 IU/mL.
Time Frame
Week 16 and Week 36
Title
Percentage of Participants With HCV NS3/4A Sequence, NS5A and NS5B After End of Treatment in Participants Not Achieving SVR
Description
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. All participants in this study achieved SVR12. Therefore, reasons for not achieving SVR12 are not applicable.
Time Frame
Baseline, Day 3, Week 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and Year 1, 1.5, 2, 2.5, 3 after end of treatment
Title
Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36)
Time Frame
Follow-up Week 24 (Week 36)
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
Description
Tmax is the time to reach maximum observed plasma concentration.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Title
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
Description
The AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after dosing.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Title
Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
Description
The Cmax is the maximum observed plasma concentration.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Title
Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
Description
The Cmin is the minimum observed plasma concentration.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Title
Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)
Description
The C0h is the pre-dose plasma concentration.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8
Title
Percentage of Participants With On-treatment Failure
Description
On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment.
Time Frame
Week 12
Title
Percentage of Participants With Viral Relapse
Description
Viral relapse is defined as participants who do 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 (15 IU/mL) at Week 16, 24 or 36.
Time Frame
Week 16, 24 and 36
Title
Percentage of Participants With SVR12 Who Maintained to Have HCV RNA <LLOQ Until the End of 3 Years Follow up
Description
Percentage of participants with SVR12 who maintained to have HCV RNA <LLOQ (15 IU/mL) until the end of 3 years follow up were reported.
Time Frame
Week 24 post treatment until the end of 3-year follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Documented chronic Hepatitis C virus (HCV) infection: diagnosis of HCV more than (>) 6 months before the Screening visit, either by detectable HCV ribonucleic acid (RNA), a HCV positive antibody or the presence of histological changes consistent with chronic hepatitis
HCV genotype 1 or 4 infection and HCV RNA plasma level >10,000 international unit per milliliter (IU/mL) (both determined at screening)
Presence of cirrhosis, which is defined as a FibroScan with a result of >14.5 kilopascals (kPa) at Screening
HCV treatment-naive participants: participant has not received treatment with any approved or investigational drug for the treatment of HCV infection and HCV treatment-experienced participants: participant has had at least 1 documented previous course of a non-direct-acting antiviral agent (DAA), interferon (IFN)-based HCV therapy (with or without Ribavirin [RBV]). Last dose in this previous course should have occurred at least 2 months prior to Screening
Decompensated liver disease: Panel 1: Child Pugh A (mild hepatic impairment) with evidence of portal hypertension [confirmed by the presence of esophageal varices on gastroscopy or hepatic venous pressure gradient (HVPG) greater than or equal to (>=) 10 millimeter of mercury (mm Hg)], Panel 2: Child-Pugh B (moderate hepatic impairment) 7 to 9 (extremes included)
Exclusion Criteria:
Co-infection with any HCV genotype
Co-infection with human immunodeficiency virus (HIV)-1 or -2 (positive HIV-1 or HIV-2 antibodies test at Screening)
Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the Investigator
Use of any disallowed therapies before the planned first dose of study drugs
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32270053
Citation
Lawitz E, Poordad F, Gutierrez JA, Beumont M, Beets G, Vandevoorde A, Remoortere PV, Luo D, Vijgen L, Eygen VV, Gamil M. Simeprevir, daclatasvir, and sofosbuvir for hepatitis C virus-infected patients: Long-term follow-up results from the open-label, Phase II IMPACT study. Health Sci Rep. 2020 Feb 22;3(2):e145. doi: 10.1002/hsr2.145. eCollection 2020 Jun.
Results Reference
derived
PubMed Identifier
27878906
Citation
Lawitz E, Poordad F, Gutierrez JA, Kakuda TN, Picchio G, Beets G, Vandevoorde A, Van Remoortere P, Jacquemyn B, Luo D, Ouwerkerk-Mahadevan S, Vijgen L, Van Eygen V, Beumont M. Simeprevir, daclatasvir and sofosbuvir for hepatitis C virus-infected patients with decompensated liver disease. J Viral Hepat. 2017 Apr;24(4):287-294. doi: 10.1111/jvh.12645. Epub 2016 Nov 23.
Results Reference
derived
Learn more about this trial
An Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease
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