A Study to Evaluate the Safety, Tolerability, and Effectiveness of a 12-Week Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Patients Infected With Chronic Genotype 1 Hepatitis C Virus
A Phase IIa, Open-label Trial to Evaluate the Safety, Tolerability and Efficacy of a 12 Weeks Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Chronic Genotype 1 Hepatitis C Infected Patients
3 other identifiers
interventional
90
2 countries
10
Brief Summary
The purpose of this study is to explore the efficacy and safety of TMC647055, TMC435, and low-dose ritonavir, administered together with and without ribavirin and of TMC647055, TMC435, low-dose ritonavir administered together with GSK233680k without ribavirin in a limited number of patients with chronic hepatitis C virus (HCV) infection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2012
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 26, 2012
CompletedStudy Start
First participant enrolled
October 1, 2012
CompletedFirst Posted
Study publicly available on registry
November 9, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2014
CompletedJanuary 11, 2016
January 1, 2016
1.9 years
September 26, 2012
January 8, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of patients with a sustained virologic response (SVR) 12 Weeks after the actual end of treatment
SVR12 is defined as undetectable HCV RNA at the actual end of treatment and HCV RNA less than 25 IU/mL at 12 Weeks after the actual end of treatment.
Week 24 (Up to 12 weeks after end-of treatment visit)
Number of patients with adverse events
Number of patients with adverse events, serious adverse events, abnormal changes in safety related laboratory values, abnormal changes in vital signs and physical examination, and abnormal echocardiogram.
Up to Week 48 (24 weeks after end of treatment)
Secondary Outcomes (17)
Number of patients with a sustained virological response (SVR at 4 and/or 24 Weeks after the actual end of treatment)
Up to 24 weeks after end of treatment
HCV RNA levels over time
Up to 24 weeks after end of treatment
Number of patients with undetectable hepatitis C virus (HCV) RNA (less than 25 IU/mL undetectable) and/or HCV RNA levels less than 25 IU/mL at all time points
Up to 24 weeks after end of treatment
Number of patients with on-treatment virologic failure
End of treatment (Week 48)
Number of patients with viral relapse
Up to 24 weeks after end of treatment
- +12 more secondary outcomes
Study Arms (7)
Panel 1
EXPERIMENTAL10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.
Panel 2 Arm 1
EXPERIMENTAL10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.
Panel 2 Arm 2
EXPERIMENTAL10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir.
Panel 3 - Arm 1
EXPERIMENTAL8 chronic HCV GT1a infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir + ribavirin.
Panel 3 - Arm 2
EXPERIMENTAL8 chronically HCV GT1b infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir.
Panel 4 - Arm 1
EXPERIMENTAL20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (30 mg once daily)
Panel 4 - Arm 2
EXPERIMENTAL20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (60 mg once daily)
Interventions
Type=exact number, unit=mg, number=150, form=capsule, route=oral. 3 or 4 capsules of 150 mg will be administered once daily.
Type=exact number, unit=mg, number=75, form=capsule, route=oral. 1 capsule of 75 mg will be administered once daily.
Type=exact number, unit=mg, number=30 or 50, form=tablet or solution, route=oral. 0.375 mL or 0.625 ml (80 mg/mL) solution will be administered once daily.
Type=exact number, unit=mg, number=200, form=tablet, route=oral. 5 to 6 (1000 or 1200 mg) tablets will be administered once daily, divided in 2 daily doses. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment 5 or 6 (depending on bodyweight) tablets of ribavirin (equivalent to 200 mg/tablet) per day, divided in 2 daily doses for an additional 12 or 36 weeks.
Type=exact number, unit=mcg, number=180, form=solution, route=subcutaneous injection. PegIFN 0.5 mL prefilled syringe equivalent to 180 mcg will be administered as a subcutaneous (under the skin) injection as follow-up (FU) treatment for 12 or 36 weeks based on follow-up treatment principles as described in the protocol. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment with Pegylated interferon alpha-2a (PegIFN) 0.5 mL prefilled syringe equivalent to 180 mcg administered as a subcutaneous (under the skin) injection for an additional 12 or 36 weeks.
Type=exact number, unit=mg, number=30 or 60, form=tablet, route=subcutaneous injection. GSK2336805 one or two 30 mg tablet(s) taken orally (by mouth) once daily for 12 weeks.
Eligibility Criteria
You may qualify if:
- Documented chronic genotype 1a or genotype 1b hepatitis C virus (HCV) infection with HCV ribonucleic acid (RNA) level \>100,000 IU/mL at screening
- Treatment-naive or documented prior relapser to previous treatment regimens and has stopped treatment at least 3 months before screening
- Liver biopsy within 3 years before the screening visit or elastography results available prior to first study drug dosing
- Medically stable based on physical examination, medical history, vital signs, and electrocardiogram performed at screening
- Body mass index of 18.0 to 32.0 kg/m2 and body weight more than 50 kg
You may not qualify if:
- Evidence of liver cirrhosis by liver biopsy or the presence of esophageal varices or a transient elastography result of \>14.6 kPa within 2 years prior to first dosing
- Evidence of decompensated liver disease defined as prior history or current evidence of ascites, hepatic encephalopathy, bleeding oesophageal or gastric varices
- Evidence of any significant liver disease in addition to hepatitis C (including but not limited to hepatitis B, drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis, or primary biliary cirrhosis)
- Receiving or has received any HCV-specific direct antiviral agent (HCV protease inhibitors, HCV nucleoside polymerase inhibitors, HCV non-nucleoside polymerase inhibitors, HCV NS5a inhibitors or any other HCV inhibitor targeting an HCV protein or a target involved in the HCV replication cycle
- Co-infected with human immunovirus (HIV)-1 or HIV-2, with non-genotype 1a/1b HCV, or hepatitis A or B virus infection
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Unknown Facility
Antwerp, Belgium
Unknown Facility
Bruges, Belgium
Unknown Facility
Brussels, Belgium
Unknown Facility
Edegem, Belgium
Unknown Facility
Ghent, Belgium
Unknown Facility
Leuven, Belgium
Unknown Facility
Liège, Belgium
Unknown Facility
Berlin, Germany
Unknown Facility
Hamburg, Germany
Unknown Facility
Mainz, Germany
Related Publications (1)
Vijgen L, Thys K, Vandebosch A, Van Remoortere P, Verloes R, De Meyer S. Virology analysis in HCV genotype 1-infected patients treated with the combination of simeprevir and TMC647055/ritonavir, with and without ribavirin, and JNJ-56914845. Virol J. 2017 May 31;14(1):101. doi: 10.1186/s12985-017-0760-2.
PMID: 28569206DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Janssen R&D Ireland Clinical Trial
Janssen R&D Ireland
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 26, 2012
First Posted
November 9, 2012
Study Start
October 1, 2012
Primary Completion
September 1, 2014
Study Completion
December 1, 2014
Last Updated
January 11, 2016
Record last verified: 2016-01