Hepatitis C
Conditions
Keywords
Hepatitis C, TMC435HPC3001, TMC435, Hepatitis C Virus (HCV), HEP C, Genotype 1, Treatment experienced, Null responders, Partial responders
Brief summary
The purpose of this study is to demonstrate the efficacy of TMC435 in combination with peginterferon (PegIFN) + ribavirin (RBV) by means of establishing its non- inferiority compared to an approved regimen of telaprevir + PegIFN + RBV in patients who have previously failed PegIFN.
Detailed description
This study is a randomized (study drug assigned by chance like flipping a coin), double-blind (neither physician nor patient knows the name of the assigned drug), double-dummy (patients receive both active and inactive pills also called placebo), 2-arm, multicenter Phase III clinical study in adult treatment experienced Chronic Hepatitis C (CHC) genotype-1 infected patients who failed to respond during at least 1 previous course of PegINFα-2a/ RBV therapy. The purpose of the trial is to study the efficacy of TMC435 in combination with PegINFα-2a and RBV for 48 weeks of treatment compared to the approved regimen of telaprevir in combination with PegINFα-2a and RBV for 48 weeks of treatment. The study will consist of a screening period (maximum 6 weeks), treatment period (48 weeks) and post-treatment period (until 72 weeks after the start of treatment). For the first 12 weeks one group of patients will take TMC435 and TVR placebo, plus PegINFα-2a and RBV. The other group will take TMC435 placebo and TVR, plus PegINFα-2a and RBV. After 12 weeks, patients in both arms will only take PegINFα-2a and RBV up to week 48. After patients stop taking study medication, they will continue to go to the doctor's office for study visits until a total of 72 weeks after they start study treatment. Patients will be monitored for safety throughout the study. Study assessments at each study visit may include, but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations.
Interventions
DRUGTMC435
TMC435 Type=exact number, unit=mg, number=150, form=capsule, route=oral use. TVR placebo Form=tablet, route=oral use. TMC435 capsule is taken once daily in addition to 2 TVR placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.
DRUGTVR
TVR Type=exact number, unit=mg, number=375, form=tablet, route=oral use. TMC435 placebo Form=capsule, route=oral use. 2 TVR tablets are taken 3 times a day together with 150 mg TMC435 placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks
Sponsors
Janssen R&D Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patient must have had a liver biopsy before screening (or between the screening and baseline visit), unless patient cannot undergo such a procedure or has evidence of portal hypertension not associated with cirrhosis. For patients who had a liver biopsy performed more than 2 years prior to screening or without a biopsy (because of a contraindication or portal hypertension), a non-invasive staging assessment needs to be available. Non-invasive staging assessments include FibroScan, MR-Elastography, or FibroTest/FibroSure and must not be older than 6 months prior to screening * Chronicity of hepatitis C virus (HCV) infection, as confirmed by one or both of the following: presence of anti-HCV antibody and/or HCV ribonucleic acid (RNA) at least 6 months prior to the screening visit and/or presence of fibrosis on biopsy * Genotype 1 HCV infection with plasma HCV RNA of \>10,000 IU/mL (both confirmed at screening) * Patient must have had at least 1 documented previous course of treatment with PegINFα-2a or PegINFα-2b in combination with ribavirin (RBV) (at least 12 weeks for null responder and 20 weeks for partial responder)
Exclusion criteria
* Hepatic decompensation (impaired functioning of the liver), as indicated by significant laboratory abnormalities or other active diseases * Infection with Human Immunodeficiency Virus (HIV) or non genotype 1 hepatitis C * Liver disease not related to hepatitis C infection * Previous chronic hepatitis C treatment, other than PegIFN and RBV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) | 12 Weeks After the Planned End of Treatment (EOT: Week 48) | Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (\<) 25 International unit per milliliter (IU/mL) undetectable; 2) HCV RNA levels \<25 IU/mL undetectable or HCV RNA levels \<25 IU/mL detectable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) | 24 Weeks After the Planned EOT (Week 48) | Participants are considered to have reached SVR24 if both conditions below are met: 1) HCV RNA levels less than \<25 International unit per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels \<25 IU/mL undetectable or HCV RNA levels \<25 IU/mL detectable (24 weeks after the planned EOT). |
| Percentage of Participants With Viral Relapse | End of Treatment (Week 48) up to Follow-up Period (until Week 72) | Participants are considered to have a viral relapse if both conditions as specified are met: 1) \<25 IU/mL undetectable HCV RNA at the actual end of study drug treatment; 2) confirmed HCV RNA greater than or equal to (\>=) 25 IU/mL during follow-up. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Norway, Poland, Portugal, Puerto Rico, Romania, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin Simeprevir (TMC435) 150 milligram (mg) capsule, orally, once daily for 12 weeks, along with 2 telaprevir (TVR) matched placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks. | 379 |
| Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin 2 Telaprevir (TVR) tablets, orally, 3 times a day along with 150 mg TMC435 matched placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks. | 384 |
| Total | 763 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Lost to Follow-up | 13 | 10 |
| Overall Study | randomized but not treated | 6 | 2 |
| Overall Study | Withdrawal by Subject | 13 | 20 |
Baseline characteristics
| Characteristic | Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Total |
|---|---|---|---|
| Age, Continuous | 50 years | 52 years | 51 years |
| Sex: Female, Male Female | 136 Participants | 161 Participants | 297 Participants |
| Sex: Female, Male Male | 243 Participants | 223 Participants | 466 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 349 / 379 | 369 / 384 |
| serious Total, serious adverse events | 22 / 379 | 54 / 384 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (\<) 25 International unit per milliliter (IU/mL) undetectable; 2) HCV RNA levels \<25 IU/mL undetectable or HCV RNA levels \<25 IU/mL detectable.
Time frame: 12 Weeks After the Planned End of Treatment (EOT: Week 48)
Population: Intent-to-treat (ITT) population included all randomized participants who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) | 53.6 percentage of participants |
| Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) | 54.7 percentage of participants |
p-value: 0.00195% CI: [-7.8, 5.5]Stratified Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Participants are considered to have reached SVR24 if both conditions below are met: 1) HCV RNA levels less than \<25 International unit per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels \<25 IU/mL undetectable or HCV RNA levels \<25 IU/mL detectable (24 weeks after the planned EOT).
Time frame: 24 Weeks After the Planned EOT (Week 48)
Population: ITT population included all randomized participants who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) | 53.3 percentage of participants |
| Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) | 55.2 percentage of participants |
Secondary
Percentage of Participants With Viral Relapse
Participants are considered to have a viral relapse if both conditions as specified are met: 1) \<25 IU/mL undetectable HCV RNA at the actual end of study drug treatment; 2) confirmed HCV RNA greater than or equal to (\>=) 25 IU/mL during follow-up.
Time frame: End of Treatment (Week 48) up to Follow-up Period (until Week 72)
Population: ITT population included all randomized participants who took at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Percentage of Participants With Viral Relapse | 17.9 percentage of participants |
| Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | Percentage of Participants With Viral Relapse | 16.4 percentage of participants |