Hepatitis CPhase 3PROMISENCT01281839
An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy
A Phase 3 study testing TMC435, Peginterferon alpha-2a (PegIFN alpha-2a) and Ribavirin (RBV) in people with Hepatitis C, run by Janssen R&D Ireland at 68 sites in 13 countries.
Trial summary
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C
- What is being tested?
- TMC435, Peginterferon alpha-2a (PegIFN alpha-2a) and Ribavirin (RBV)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 394 participants
- Where
- 68 sitesin 13 countries
- Study dates
- Feb 2011to Feb 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Genotype 1 hepatitis C infection (confirmed at screening)
- Have previously received peginterferon-based therapy for at least 24 weeks with documented HCV RNA at last measurement and relapsed within 1 year of last taking medication
- Liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection
- Must agree to use 2 forms of effective contraception throughout study (both males and females)
Who cannot join
- Infection with HIV or non-genotype 1 hepatitis C
- Liver disease not related to hepatitic C infection
- Hepatic decompensation
- Significant laboratory abnormalities or other active diseases
- Pregnant or planning to become pregnant
Trial locations and contacts
68 sites in 13 countries.
68 sites in 13 countries
United States11 sites
Study site
Atlanta, Georgia
Study site
Aurora, Colorado
Study site
Bakersfield, California
Study site
Crestview Hills, Kentucky
Study site
Germantown, Tennessee
Study site
Houston, Texas
Study site
Jackson, Mississippi
Study site
Jacksonville, Florida
Study site
Orlando, Florida
Study site
Saint Paul, Minnesota
Study site
San Antonio, Texas
Germany10 sites
Study site
Berlin
Study site
Düsseldorf
Study site
Frankfurt
Study site
Freiburg im Breisgau
Study site
Halle
Study site
Hamburg
Study site
Kiel
Study site
Leipzig
Study site
München
Study site
Würzburg
France7 sites
Study site
Créteil
Study site
Grenoble
Study site
Lyon
Study site
Nice
Study site
Paris
Study site
Rennes
Study site
Vandœuvre-lès-Nancy
Poland6 sites
Study site
Bialystok
Study site
Bydgoszcz
Study site
Czeladź
Study site
Kielce
Study site
Krakow
Study site
Warsaw
Australia5 sites
Study site
Adelaide
Study site
Kingswood
Study site
Melbourne
Study site
Sydney
Study site
Woolloongabba
Belgium5 sites
Study site
Antwerp
Study site
Bruges
Study site
Brussels
Study site
Ghent
Study site
Leuven
Russia5 sites
Study site
Moscow
Study site
Saint Petersburg
Study site
Samara
Study site
Smolensk
Study site
Stavropol
United Kingdom5 sites
Study site
Birmingham
Study site
Derby
Study site
Glasgow
Study site
London
Study site
Plymouth
Canada4 sites
Study site
Montreal, Quebec
Study site
Ottawa, Ontario
Study site
Toronto, Ontario
Study site
Vancouver, British Columbia
Spain4 sites
Study site
Barcelona
Study site
Madrid
Study site
Seville
Study site
Valencia
New Zealand3 sites
Study site
Auckland
Study site
Christchurch
Study site
Hamilton
About this study
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon α-2a and Ribavirin in Hepatitis C, Genotype 1 Infected Subjects Who Relapsed After Previous Interferon-based Therapy
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment.
Read the detailed description
This is a randomized, double-blind (neither physician nor patients knows the name of the assigned drug), placebo-controlled study of TMC435 in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients in this study will also receive two other drugs for their infection called peginterferon alfa-2a and ribavirin. The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, patients will take TMC435 or placebo, plus peginterferon alfa-2a and ribavirin. For the next 12 weeks, patients will take peginterferon alfa-2a and ribavirin only. After that, some patients will continue to take peginterferon alfa-2a and ribavirin for up to 24 additional weeks. Other patients will stop taking peginterferon alfa-2a and ribavirin. The study doctor will inform each patient about how to take their study medication and when they should stop taking it. After a patient stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). 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, ECG assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Ribavirin (Copegus ®) will be taken as a tablet twice each day and the dose will depend on your body weight.
- Conditions
- Hepatitis C
- Being tested
- TMC435, Placebo, Peginterferon alpha-2a (PegIFN alpha-2a), Ribavirin (RBV)
- Keywords
- Hepatitis C, TMC435, HCV, Hep C, Genotype 1
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC435Drug
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks
PlaceboDrug
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks
Peginterferon alpha-2a (PegIFN alpha-2a)Drug
Also called Pegasys
One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks.
Ribavirin (RBV)Drug
Also called Copegus
200-mg tablets of RBV (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| TMC435 | Experimental | TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks Receives: Drug: TMC435; Drug: Peginterferon alpha-2a (PegIFN alpha-2a); Drug: Ribavirin (RBV) |
| Placebo | Placebo comparator | Placebo 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks Receives: Drug: Placebo; Drug: Peginterferon alpha-2a (PegIFN alpha-2a); Drug: Ribavirin (RBV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
Measured: Week 36 or Week 60
Secondary outcomes (29)
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.
Measured: Week 72
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment.
Measured: Week 48 or Week 72
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment.
Measured: Week 28 or Week 52
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows change from baseline in log10 HCV RNA levels.
Measured: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows actual values of log10 HCV RNA levels. From Week 4 onwards, most participants in TMC 435 150mg 12Wks PR24/48 group had plasma HCV RNA levels below the limit of detection of the HCV RNA assay.
Measured: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
The Percentage of Participants With On-treatment Virologic Response at All Time Points
The table below shows the percentage of participants with HCV ribonucleic acid (RNA plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA.
Measured: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.
Measured: Week 4
The Percentage of Participants Achieving a Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of greater than or equal to 2 log10 at Week 12.
Measured: Week 12
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.
Measured: Week 12
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12.
Measured: Week 4 and Week 12
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
The table below shows the percentage of participants in each treatment group with <1 log10 HCV RNA decrease at Week 4.
Measured: Week 4
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
The table below shows the percentage of participants in each treatment group with HCV RNA levels >1000 IU/mL at Week 4.
Measured: Week 4
The Percentage of Participants With Null Response
The table below shows the percentage of participants with null response, defined as <2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline.
Measured: Week 12
The Percentage of Participants With Partial Response
The table below shows the percentage of participants with partial response, defined as =>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment.
Measured: Week 12
The Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable).
Measured: Up to Week 48
The Percentage of Participants With Viral Relapse
The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.
Measured: Up to Week 72
The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus [HCV] ribonucleic acid [RNA] levels <25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks.
Measured: Week 24
The Percentage of Participants With On-treatment Failure
The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment.
Measured: Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
The table below shows mean time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable.
Measured: Up to Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
The table below shows mean time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable.
Measured: Up to Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
The table below shows mean time in days to reach HCV RNA levels <100 IU/mL.
Measured: Up to Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
The table below shows mean time in days to reach HCV RNA levels <1000 IU/mL.
Measured: Up to Week 48
The Percentage of Participants With Viral Breakthrough at Different Time Points
The table below shows the percentage of participants at different time points with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable).
Measured: Up to Week 48
Time From End-of-treatment to Viral Relapse
The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment.
Measured: Up to Week 72
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 156 of 260 participants in the TMC435 treatment group and 84 of 133 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range.
Measured: Up to Week 48
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
The table below shows the median time to normalization of ALT levels.
Measured: Up to Week 48
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours (AUC 24hr) after dosing for TMC435. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then the median of AUC value across visits for each participant was used to calculate the mean AUC 24 hr for the study.
Measured: From the time of administration up to 24 hours after dosing through Week 12
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
The table below shows mean (standard deviation) of C0h values of TMC435. To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then the median of C0h values across visits for each participant was used to calculate the mean C0h for the study.
Measured: Before administration of TMC435 through Week 12
Plasma Concentration of TMC435: Systemic Clearance (CL)
The table below shows mean (standard deviation) of CL values of TMC435. To calculate the mean CL for the study, CL values were derived for each participant at each visit and then the median of CL values across visits for each participant was used to calculate the mean CL for the study.
Measured: From the time of administration through Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2011 (estimated)
- Study startFeb 2011
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 394 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen R&D Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen R&D Ireland Clinical Trial, Study director, Janssen R&D Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01281839
- Sponsor's protocol ID
- CR017371
- Other IDs
- TMC435HPC3007, 2010-021113-23
- Acronym
- PROMISE
- Status last verified
- Mar 2014
- First submitted
- 7 Jan 2011
- Last updated
- 23 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28.
PubMed 25445400Forns X, Lawitz E, Zeuzem S, Gane E, Bronowicki JP, Andreone P, Horban A, Brown A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, Scott J, De La Rosa G, Kalmeijer R, Sinha R, Beumont-Mauviel M. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology. 2014 Jun;146(7):1669-79.e3. doi: 10.1053/j.gastro.2014.02.051. Epub 2014 Mar 3.
PubMed 24602923
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon α-2a and Ribavirin in Hepatitis C, Genotype 1 Infected Subjects Who Relapsed After Previous Interferon-based Therapy
- ClinicalTrials.gov ID
- NCT01281839
- Acronym / sponsor ID
- PROMISE / CR017371
- Conditions
- Hepatitis C
- Keywords
- Hepatitis C, TMC435, HCV, Hep C, Genotype 1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 394 participants (actual)
- Lead sponsor
- Janssen R&D IrelandIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 24 Jan 2011 (estimated)
- Results
- Posted 23 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment.
Detailed description
This is a randomized, double-blind (neither physician nor patients knows the name of the assigned drug), placebo-controlled study of TMC435 in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients in this study will also receive two other drugs for their infection called peginterferon alfa-2a and ribavirin. The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, patients will take TMC435 or placebo, plus peginterferon alfa-2a and ribavirin. For the next 12 weeks, patients will take peginterferon alfa-2a and ribavirin only. After that, some patients will continue to take peginterferon alfa-2a and ribavirin for up to 24 additional weeks. Other patients will stop taking peginterferon alfa-2a and ribavirin. The study doctor will inform each patient about how to take their study medication and when they should stop taking it. After a patient stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). 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, ECG assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Ribavirin (Copegus ®) will be taken as a tablet twice each day and the dose will depend on your body weight.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TMC435 | Experimental | Drug: TMC435, Drug: Peginterferon alpha-2a (PegIFN alpha-2a), Drug: Ribavirin (RBV)TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Peginterferon alpha-2a (PegIFN alpha-2a), Drug: Ribavirin (RBV)Placebo 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Genotype 1 hepatitis C infection (confirmed at screening)
- Have previously received peginterferon-based therapy for at least 24 weeks with documented HCV RNA at last measurement and relapsed within 1 year of last taking medication
- Liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection
- Must agree to use 2 forms of effective contraception throughout study (both males and females)
Key exclusion criteria (5 listed)
- Infection with HIV or non-genotype 1 hepatitis C
- Liver disease not related to hepatitic C infection
- Hepatic decompensation
- Significant laboratory abnormalities or other active diseases
- Pregnant or planning to become pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMC435150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks | Drug | TMC435 |
| Placebo150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks | Drug | Placebo |
| Peginterferon alpha-2a (PegIFN alpha-2a)Also: PegasysOne subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks. | Drug | Placebo, TMC435 |
| Ribavirin (RBV)Also: Copegus200-mg tablets of RBV (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks. | Drug | Placebo, TMC435 |
Primary outcome
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Time frame: Week 36 or Week 60
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
29 secondary outcomes
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
Time frame: Week 72
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Time frame: Week 48 or Week 72
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
Time frame: Week 28 or Week 52
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Time frame: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Time frame: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
The Percentage of Participants With On-treatment Virologic Response at All Time Points
Time frame: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Time frame: Week 4
The Percentage of Participants Achieving a Early Virologic Response (EVR)
Time frame: Week 12
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
Time frame: Week 12
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
Time frame: Week 4 and Week 12
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
Time frame: Week 4
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
Time frame: Week 4
The Percentage of Participants With Null Response
Time frame: Week 12
The Percentage of Participants With Partial Response
Time frame: Week 12
The Percentage of Participants With Viral Breakthrough
Time frame: Up to Week 48
The Percentage of Participants With Viral Relapse
Time frame: Up to Week 72
The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
Time frame: Week 24
The Percentage of Participants With On-treatment Failure
Time frame: Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
Time frame: Up to Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
Time frame: Up to Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
Time frame: Up to Week 48
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
Time frame: Up to Week 48
The Percentage of Participants With Viral Breakthrough at Different Time Points
Time frame: Up to Week 48
Time From End-of-treatment to Viral Relapse
Time frame: Up to Week 72
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
Time frame: Up to Week 48
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
Time frame: Up to Week 48
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
Time frame: From the time of administration up to 24 hours after dosing through Week 12
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
Time frame: Before administration of TMC435 through Week 12
Plasma Concentration of TMC435: Systemic Clearance (CL)
Time frame: From the time of administration through Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25445400Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28.
- Derived from this study: PubMed 24602923Forns X, Lawitz E, Zeuzem S, Gane E, Bronowicki JP, Andreone P, Horban A, Brown A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, Scott J, De La Rosa G, Kalmeijer R, Sinha R, Beumont-Mauviel M. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology. 2014 Jun;146(7):1669-79.e3. doi: 10.1053/j.gastro.2014.02.051. Epub 2014 Mar 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen R&D Ireland Clinical Trial study director
Janssen R&D Ireland
68 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TMC435, Peginterferon alpha-2a (PegIFN alpha-2a) and Ribavirin (RBV) in people with Hepatitis C, run by Janssen R&D Ireland at 68 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in United States, Germany, France, Poland, Australia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) (time frame: Week 36 or Week 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01281839, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2014.