Hepatitis C, ChronicPhase 3NCT01725529
An Efficacy, Pharmacokinetics, Safety and Tolerability Study of TMC435 as Part of a Treatment Regimen for Hepatitis C-Infected Patients
A Phase 3 study testing TMC435, Peginterferon-alpha (PegIFNα-2a) and Ribavirin (RBV) in people with Hepatitis C, Chronic, run by Janssen R&D Ireland at 21 sites in 2 countries.
Trial summary
The purpose of this study is to provide confirmatory efficacy and safety data of TMC435 as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) in patients with genotype 1 Hepatitis C virus (HCV) infection. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- TMC435, Peginterferon-alpha (PegIFNα-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
- 457 participants
- Where
- 21 sitesin 2 countries
- Study dates
- Nov 2012to Nov 2014
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A liver biopsy within 3 years prior to the screening visit (or between screening and day of randomization) with histology consistent with chronic Hepatitis C virus (HCV) infection
- Presence of contraindications for a liver biopsy in patients who are otherwise deemed eligible for participation does not exclude the patient from participation
- Genotype 1 HCV infection (confirmed at screening)
- Plasma HCV RNA of > 10,000 IU/mL at screening
Who cannot join
- Prior treatment with any approved or investigational drug for the treatment of hepatitis C
- Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
China16 sites
Study site
Beijing
Study site
Changchun
Study site
Changsha
Study site
Chengdu
Study site
Chongqing
Study site
Guangzhou
Study site
Hangzhou
Study site
Harbin
Study site
Jinan
Study site
Lanzhou
Study site
Nanjing
Study site
Shanghai
Study site
Shenyang
Study site
Tianjin
Study site
Wuhan
Study site
Zhengzhou
South Korea5 sites
Study site
Busan
Study site
Chuncheon, Gangwon-Do
Study site
Gyeongsangnam-Do
Study site
Incheon
Study site
Seoul
About this study
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve, Genotype 1 Hepatitis C-Infected Subjects
The purpose of this study is to provide confirmatory efficacy and safety data of TMC435 as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) in patients with genotype 1 Hepatitis C virus (HCV) infection.
Read the detailed description
This is a multicenter, randomized (study drug is assigned by chance), double-blind (neither sponsor, physician nor patient knows the name of the assigned study drug), Phase III study to compare the efficacy, tolerability and safety of TMC435 (in development for treatment of chronic hepatitis C virus [HCV] infection) versus placebo (a preparation containing no drug used as control) as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) (both current therapies for HCV) in adult treatment-naïve patients (patients who have never taken HCV medications) with genotype 1 Hepatitis C virus (HCV) infection. The study will consist of a screening period with a maximum duration of 6 weeks, a response guided 24- or 48-week (TMC435 treatment groups) or 48-week (control group) treatment period, and a post-therapy follow-up period up to 72 weeks after the start of treatment. Patients will be randomly assigned in a 1:1:1 fashion to receive TMC435 or placebo, stratified by HCV genotype 1 subtype and IL28B genotype within each country. In the first 24 weeks, patients will receive 12 weeks TMC435 100 or 150 mg or placebo once-daily (q.d.) plus PegIFNα-2a plus RBV, after which they will continue with PegIFNα-2a and RBV. Response-guided treatment criteria will be used to determine PegIFNα-2a and RBV total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. In the control group, all patients will be required to complete 48 weeks of treatment with PegIFNα-2a and RBV. In all 3 treatment groups, there will be a post-therapy follow-up period up to 72 weeks after the start of treatment. The total study duration for each patient will be a maximum of 78 weeks (including the 6-week screening period).
- Conditions
- Hepatitis C, Chronic
- Being tested
- TMC435, Peginterferon-alpha (PegIFNα-2a), Ribavirin (RBV), Placebo
- Keywords
- Hepatitis C, Chronic, TMC435, Ribavirin, peginterferon-alpha (PegIFNα-2a)
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC435Drug
TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).
Peginterferon-alpha (PegIFNα-2a)Drug
PegIFNα-2a (180 micrograms [μg] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks.
Ribavirin (RBV)Drug
Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is < 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is > or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks.
PlaceboDrug
Matching placebo capsules taken orally with food once-daily for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| TMC435 150 mg | Experimental | Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48. Receives: Drug: TMC435; Drug: Peginterferon-alpha (PegIFNα-2a); Drug: Ribavirin (RBV) |
| TMC435 100 mg | Experimental | Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48. Receives: Drug: TMC435; Drug: Peginterferon-alpha (PegIFNα-2a); Drug: Ribavirin (RBV) |
| Control | Placebo comparator | Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks. Receives: Drug: Peginterferon-alpha (PegIFNα-2a); Drug: Ribavirin (RBV); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) undetectable at end of treatment and, 2). the HCV RNA is < LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.
Measured: 12 weeks after the end of treatment (EOT: Week 24 or 48)
Secondary outcomes (6)
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)
Participants considered to have achieved SVR24 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ;25 IU/mL) undetectable at end of treatment and, 2). the HCV RNA is < LLOQ detectable or undetectable at 24 weeks after the planned end of study drug treatment.
Measured: 24 weeks after the end of treatment (EOT: Week 24 or 48)
Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)
Measured: Week 72
Percentage of Participants With On-treatment Failure
A participant with on-treatment failure refers to a participant with confirmed detectable HCV RNA at the end of treatment.
Measured: End of Treatment (EOT: Week 24 or 48)
Percentage of Participants With Viral Breakthrough
The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma. Viral breakthrough was defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in subjects whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment.
Measured: Week 24 or 48 (End of Treatment)
Percentage of Participants With Viral Relapse
Viral relapse was defined as undetectable HCV RNA at the actual end of treatment and last HCV RNA measurement during follow-up ≥25 IU/mL.
Measured: 72 weeks after the EOT (Week 24 or 48)
Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level
Percentage of participants with on-treatment normalization of alanine aminotransferase level were assessed.
Measured: 72 weeks after the EOT (Week 24 or 48)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionAug 2014
- Study completionNov 2014
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.
- Other trials for Hepatitis C, ChronicStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 457 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
- NCT01725529
- Sponsor's protocol ID
- CR017962
- Other IDs
- TMC435HPC3005
- Status last verified
- Jul 2015
- First submitted
- 9 Nov 2012
- Last updated
- 13 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve, Genotype 1 Hepatitis C-Infected Subjects
- ClinicalTrials.gov ID
- NCT01725529
- Acronym / sponsor ID
- CR017962
- Conditions
- Hepatitis C, Chronic
- Keywords
- Hepatitis C, Chronic, TMC435, Ribavirin, peginterferon-alpha (PegIFNα-2a)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 457 participants (actual)
- Lead sponsor
- Janssen R&D IrelandIndustry (pharma, biotech, devices)
- Study start
- Nov 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 14 Nov 2012 (estimated)
- Results
- Posted 13 Aug 2015
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 provide confirmatory efficacy and safety data of TMC435 as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) in patients with genotype 1 Hepatitis C virus (HCV) infection.
Detailed description
This is a multicenter, randomized (study drug is assigned by chance), double-blind (neither sponsor, physician nor patient knows the name of the assigned study drug), Phase III study to compare the efficacy, tolerability and safety of TMC435 (in development for treatment of chronic hepatitis C virus [HCV] infection) versus placebo (a preparation containing no drug used as control) as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) (both current therapies for HCV) in adult treatment-naïve patients (patients who have never taken HCV medications) with genotype 1 Hepatitis C virus (HCV) infection. The study will consist of a screening period with a maximum duration of 6 weeks, a response guided 24- or 48-week (TMC435 treatment groups) or 48-week (control group) treatment period, and a post-therapy follow-up period up to 72 weeks after the start of treatment. Patients will be randomly assigned in a 1:1:1 fashion to receive TMC435 or placebo, stratified by HCV genotype 1 subtype and IL28B genotype within each country. In the first 24 weeks, patients will receive 12 weeks TMC435 100 or 150 mg or placebo once-daily (q.d.) plus PegIFNα-2a plus RBV, after which they will continue with PegIFNα-2a and RBV. Response-guided treatment criteria will be used to determine PegIFNα-2a and RBV total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. In the control group, all patients will be required to complete 48 weeks of treatment with PegIFNα-2a and RBV. In all 3 treatment groups, there will be a post-therapy follow-up period up to 72 weeks after the start of treatment. The total study duration for each patient will be a maximum of 78 weeks (including the 6-week screening period).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TMC435 150 mg | Experimental | Drug: TMC435, Drug: Peginterferon-alpha (PegIFNα-2a), Drug: Ribavirin (RBV)Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48. |
| TMC435 100 mg | Experimental | Drug: TMC435, Drug: Peginterferon-alpha (PegIFNα-2a), Drug: Ribavirin (RBV)Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48. |
| Control | Placebo comparator | Drug: Peginterferon-alpha (PegIFNα-2a), Drug: Ribavirin (RBV), Drug: PlaceboPatients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- A liver biopsy within 3 years prior to the screening visit (or between screening and day of randomization) with histology consistent with chronic Hepatitis C virus (HCV) infection
- Presence of contraindications for a liver biopsy in patients who are otherwise deemed eligible for participation does not exclude the patient from participation
- Genotype 1 HCV infection (confirmed at screening)
- Plasma HCV RNA of > 10,000 IU/mL at screening
Key exclusion criteria (2 listed)
- Prior treatment with any approved or investigational drug for the treatment of hepatitis C
- Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
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 |
|---|---|---|
| TMC435TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12). | Drug | TMC435 100 mg, TMC435 150 mg |
| Peginterferon-alpha (PegIFNα-2a)PegIFNα-2a (180 micrograms [μg] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks. | Drug | Control, TMC435 100 mg, TMC435 150 mg |
| Ribavirin (RBV)Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is < 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is > or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks. | Drug | Control, TMC435 100 mg, TMC435 150 mg |
| PlaceboMatching placebo capsules taken orally with food once-daily for 48 weeks. | Drug | Control |
Primary outcome
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Time frame: 12 weeks after the end of treatment (EOT: Week 24 or 48)
Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) undetectable at end of treatment and, 2). the HCV RNA is < LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.
6 secondary outcomes
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)
Time frame: 24 weeks after the end of treatment (EOT: Week 24 or 48)
Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)
Time frame: Week 72
Percentage of Participants With On-treatment Failure
Time frame: End of Treatment (EOT: Week 24 or 48)
Percentage of Participants With Viral Breakthrough
Time frame: Week 24 or 48 (End of Treatment)
Percentage of Participants With Viral Relapse
Time frame: 72 weeks after the EOT (Week 24 or 48)
Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level
Time frame: 72 weeks after the EOT (Week 24 or 48)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
21 sites in 2 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 (PegIFNα-2a) and Ribavirin (RBV) in people with Hepatitis C, Chronic, run by Janssen R&D Ireland at 21 sites in 2 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 2 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 13 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in China, South Korea. 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 13 Aug 2015). 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?
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) (time frame: 12 weeks after the end of treatment (EOT: Week 24 or 48)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Aug 2015.