Hepatitis CPhase 2ASPIRENCT00980330
A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard Treatment
A Phase 2 study testing TMC435, Peg-IFN-alfa-2a (P) and Ribavirin (R) in people with Hepatitis C, run by Tibotec Pharmaceuticals, Ireland at 78 sites in 14 countries.
Trial summary
The purpose of this study is to determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- TMC435, Peg-IFN-alfa-2a (P) and Ribavirin (R)
- 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
- 463 participants
- Where
- 78 sitesin 14 countries
- Study dates
- Oct 2009to Aug 2011
- Phase
- Phase 2
- 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
- Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
- Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
- Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
- Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication
Who cannot join
- Has an evidence of decompensated liver disease
- Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
- Has a medical condition which is a contraindication to Peg-INF or RBV therapy
- Have had history of, or any current medical condition which could impact the safety of the patient in the study
Trial locations and contacts
78 sites in 14 countries.
78 sites in 14 countries
United States17 sites
Study site
Chapel Hill, North Carolina
Study site
Chicago, Illinois
Study site
Cincinnati, Ohio
Study site
Germantown, Tennessee
Study site
Jackson, Mississippi
Study site
Jacksonville, Florida
Study site
La Jolla, California
Study site
Laurel, Maryland
Study site
Los Angeles, California
Study site
Miami, Florida
Study site
Nashville, Tennessee
Study site
New Orleans, Louisiana
Study site
New York, New York
Study site
Orlando, Florida
Study site
Palm Harbor, Florida
Study site
San Antonio, Texas
Study site
Tupelo, Mississippi
Australia8 sites
Study site
Concord
Study site
Darlinghurst
Study site
Fitzroy
Study site
Melbourne
Study site
New Lambton Heights
Study site
Parkville
Study site
Sydney
Study site
Woolloongabba
Germany8 sites
Study site
Berlin
Study site
Cologne
Study site
Düsseldorf
Study site
Frankfurt A. M.
Study site
Freiburg im Breisgau
Study site
Hanover
Study site
Stuttgart
Study site
Würzburg
Israel7 sites
Study site
Haifa
Study site
Jerusalem
Study site
Nazareth
Study site
Petah Tikva
Study site
Ramat Gan
Study site
Safed
Study site
Tel Aviv
Belgium6 sites
Study site
Bruges
Study site
Brussels
Study site
Edegem
Study site
Ghent
Study site
Leuven
Study site
Roeselare
France6 sites
Study site
Créteil
Study site
Grenoble
Study site
Lyon
Study site
Nice
Study site
Paris
Study site
Vandœuvre-lès-Nancy
Poland5 sites
Study site
Bialystok
Study site
Bydgoszcz
Study site
Czeladź
Study site
Kielce
Study site
Warsaw
Russia5 sites
Study site
Moscow
Study site
Nizhny Novgorod
Study site
Saint Petersburg
Study site
Samara
Study site
Smolensk
Canada4 sites
Study site
Calgary, Alberta
Study site
Montreal, Quebec
Study site
Ottawa, Ontario
Study site
Toronto, Ontario
New Zealand3 sites
Study site
Auckland
Study site
Christchurch
Study site
Hamilton
About this study
Official title: A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy
The purpose of this study is to determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).
Read the detailed description
The study is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who have failed standard treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF-alfa-2a and RBV) versus standard treatment alone. The trial will consist of a screening period of maximum 6 weeks, a 48-week treatment period, and a 24-week follow-up period. Participants will be eligible to enroll in the trial if they failed to respond to a prior course of standard treatment or relapsed following standard treatment. Participants will be randomly assigned to receive TMC435 with standard treatment for 12 weeks followed by standard treatment (plus placebo) for 36 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks followed by standard treatment (plus placebo) for 24 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks, or a placebo with standard treatment for 48 weeks.
- Conditions
- Hepatitis C
- Being tested
- TMC435, Placebo, Peg-IFN-alfa-2a (P), Ribavirin (R)
- Keywords
- Hepatitis C, Peginterferon alpha-2a, PegIFNalpha-2a, RBV, Ribavirin, Placebo, TMC435-TIDP16-C206, TMC435-C206, TMC435, HCV
- 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
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
PlaceboDrug
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.
Peg-IFN-alfa-2a (P)Drug
Also called PEGASYS
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Ribavirin (R)Drug
Also called COPEGUS
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| TMC435 100 mg 12 Wks + PR48 | Experimental | Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. Receives: Drug: TMC435; Drug: Placebo; Drug: Peg-IFN-alfa-2a (P); Drug: Ribavirin (R) |
| TMC435 100 mg 24 Wks + PR48 | Experimental | Participants willl receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. Receives: Drug: TMC435; Drug: Placebo; Drug: Peg-IFN-alfa-2a (P); Drug: Ribavirin (R) |
| TMC435 100 mg 48 Wks + PR48 | Experimental | Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Receives: Drug: TMC435; Drug: Placebo; Drug: Peg-IFN-alfa-2a (P); Drug: Ribavirin (R) |
| TMC435 150 mg 12 Wks + PR48 | Experimental | Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. Receives: Drug: TMC435; Drug: Placebo; Drug: Peg-IFN-alfa-2a (P); Drug: Ribavirin (R) |
| TMC435 150 mg 24 Wks + PR48 | Experimental | Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. Receives: Drug: TMC435; Drug: Placebo; Drug: Peg-IFN-alfa-2a (P); Drug: Ribavirin (R) |
| TMC435 150 mg 48 Wks + PR48 | Experimental | Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Receives: Drug: TMC435; Drug: Peg-IFN-alfa-2a (P); Drug: Ribavirin (R) |
| Placebo 48 Wks + PR48 | Placebo comparator | Participants will receive Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. Receives: Drug: TMC435; Drug: Peg-IFN-alfa-2a (P); Drug: Ribavirin (R) |
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 at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24)
The table below shows the percentage of participants in the overall population with an SVR24, defined as having plasma levels of Hepatitis C Virus ribonucleic acid less than 25 IU/mL undetectable at the EOT and 24 weeks after the EOT.
Measured: Week 72
Secondary outcomes (12)
The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment
The table below shows the percentage of participants in each treatment group who achieved a greater than 2 log10 drop in plasma levels of HCV RNA at selected time points during treatment.
Measured: Weeks, 2, 4, 8, and 12
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up
The table below shows the percentage of participants in each treatment who achieved plasma HCV RNA levels of <25 IU/mL undetectable at selected time points during treatment and follow-up and at the end of treatment (EOT).
Measured: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up
The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels below the limit of quantification defined as less than 25 IU/mL (detectable or undetectable) at selected time points during treatment, follow-up, and at the end of treatment (EOT).
Measured: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
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 an undetectable plasma Hepatitis C virus ribonucleic acid level after receiving 4 weeks of treatment.
Measured: Week 4
The Percentage of Participants Achieving an Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a greater than or equal to 2 log10 reduction in plasma Hepatitis C virus ribonucleic acid from baseline 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 levels of Hepatitis C virus ribonucleic acid at Week 12.
Measured: Week 12
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 the overall population who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the planned EOT.
Measured: Week 60
The Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants in the overall population in each treatment group during the treatment period who experienced viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in Hepatitis C virus (HCV) ribonucleic acid (RNA) from the lowest level reached or a confirmed HCV RNA of > 100 IU/mL in participants whose HCV RNA had previously been below the lower limit of quantification (i.e., less than 25 IU/mL detectable or undetectable).
Measured: EOT (up to Week 48)
The Percentage of Participants With Viral Relapse
The table below shows the percentage of participants in the overall population who had viral relapse, defined as confirmed detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with HCV RNA less than 25 IU/mL undetectable at end of treatment.
Measured: Up to Week 72
The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT)
The table below shows the number of participants with abnormal ALT levels at Baseline who achieved the normal ALT levels at the EOT (up to Week 48).
Measured: EOT (up to Week 48)
Plasma Concentrations of TMC435
The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for TMC435 for participants in each of the 6 TMC435 treatment groups.
Measured: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
The table below shows the median (range) AUC24h values for TMC435 for participants in each TMC435 treatment group.
Measured: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionAug 2011
- Study completionAug 2011
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 (3)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 463 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals, Ireland Clinical Trial, Study director, Tibotec Pharmaceuticals, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00980330
- Sponsor's protocol ID
- CR016063
- Other IDs
- TMC435-TiDP16-C206, 2009-010590-20, 2009
- Acronym
- ASPIRE
- Status last verified
- May 2014
- First submitted
- 10 Sep 2009
- Last updated
- 9 Jun 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 25445400Scott J, Rosa K, Fu M, Cerri K, Peeters M, Beumont M, Zeuzem S, Evon DM, Gilles L. Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection. BMC Infect Dis. 2014 Aug 26;14:465. doi: 10.1186/1471-2334-14-465.
PubMed 25164700Zeuzem S, Berg T, Gane E, Ferenci P, Foster GR, Fried MW, Hezode C, Hirschfield GM, Jacobson I, Nikitin I, Pockros PJ, Poordad F, Scott J, Lenz O, Peeters M, Sekar V, De Smedt G, Sinha R, Beumont-Mauviel M. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology. 2014 Feb;146(2):430-41.e6. doi: 10.1053/j.gastro.2013.10.058. Epub 2013 Nov 1.
PubMed 24184810
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy
- ClinicalTrials.gov ID
- NCT00980330
- Acronym / sponsor ID
- ASPIRE / CR016063
- Conditions
- Hepatitis C
- Keywords
- Hepatitis C, Peginterferon alpha-2a, PegIFNalpha-2a, RBV, Ribavirin, Placebo, TMC435-TIDP16-C206, TMC435-C206
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 463 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 21 Sep 2009 (estimated)
- Results
- Posted 6 Feb 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 determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).
Detailed description
The study is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who have failed standard treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF-alfa-2a and RBV) versus standard treatment alone. The trial will consist of a screening period of maximum 6 weeks, a 48-week treatment period, and a 24-week follow-up period. Participants will be eligible to enroll in the trial if they failed to respond to a prior course of standard treatment or relapsed following standard treatment. Participants will be randomly assigned to receive TMC435 with standard treatment for 12 weeks followed by standard treatment (plus placebo) for 36 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks followed by standard treatment (plus placebo) for 24 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks, or a placebo with standard treatment for 48 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| TMC435 100 mg 12 Wks + PR48 | Experimental | Drug: TMC435, Drug: Placebo, Drug: Peg-IFN-alfa-2a (P), Drug: Ribavirin (R)Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks. |
| TMC435 100 mg 24 Wks + PR48 | Experimental | Drug: TMC435, Drug: Placebo, Drug: Peg-IFN-alfa-2a (P), Drug: Ribavirin (R)Participants willl receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks. |
| TMC435 100 mg 48 Wks + PR48 | Experimental | Drug: TMC435, Drug: Placebo, Drug: Peg-IFN-alfa-2a (P), Drug: Ribavirin (R)Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. |
| TMC435 150 mg 12 Wks + PR48 | Experimental | Drug: TMC435, Drug: Placebo, Drug: Peg-IFN-alfa-2a (P), Drug: Ribavirin (R)Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks. |
| TMC435 150 mg 24 Wks + PR48 | Experimental | Drug: TMC435, Drug: Placebo, Drug: Peg-IFN-alfa-2a (P), Drug: Ribavirin (R)Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks. |
| TMC435 150 mg 48 Wks + PR48 | Experimental | Drug: TMC435, Drug: Peg-IFN-alfa-2a (P), Drug: Ribavirin (R)Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks. |
| Placebo 48 Wks + PR48 | Placebo comparator | Drug: TMC435, Drug: Peg-IFN-alfa-2a (P), Drug: Ribavirin (R)Participants will receive Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily 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)
- Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
- Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
- Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
- Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication
Key exclusion criteria (4 listed)
- Has an evidence of decompensated liver disease
- Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
- Has a medical condition which is a contraindication to Peg-INF or RBV therapy
- Have had history of, or any current medical condition which could impact the safety of the patient in the study
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 |
|---|---|---|
| TMC435One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks. | Drug | Placebo 48 Wks + PR48, TMC435 100 mg 12 Wks + PR48, TMC435 100 mg 24 Wks + PR48, TMC435 100 mg 48 Wks + PR48, TMC435 150 mg 12 Wks + PR48, TMC435 150 mg 24 Wks + PR48, TMC435 150 mg 48 Wks + PR48 |
| PlaceboOne or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks. | Drug | TMC435 100 mg 12 Wks + PR48, TMC435 100 mg 24 Wks + PR48, TMC435 100 mg 48 Wks + PR48, TMC435 150 mg 12 Wks + PR48, TMC435 150 mg 24 Wks + PR48 |
| Peg-IFN-alfa-2a (P)Also: PEGASYS180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks. | Drug | Placebo 48 Wks + PR48, TMC435 100 mg 12 Wks + PR48, TMC435 100 mg 24 Wks + PR48, TMC435 100 mg 48 Wks + PR48, TMC435 150 mg 12 Wks + PR48, TMC435 150 mg 24 Wks + PR48, TMC435 150 mg 48 Wks + PR48 |
| Ribavirin (R)Also: COPEGUS1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks. | Drug | Placebo 48 Wks + PR48, TMC435 100 mg 12 Wks + PR48, TMC435 100 mg 24 Wks + PR48, TMC435 100 mg 48 Wks + PR48, TMC435 150 mg 12 Wks + PR48, TMC435 150 mg 24 Wks + PR48, TMC435 150 mg 48 Wks + PR48 |
Primary outcome
The Percentage of Participants Achieving a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24)
Time frame: Week 72
The table below shows the percentage of participants in the overall population with an SVR24, defined as having plasma levels of Hepatitis C Virus ribonucleic acid less than 25 IU/mL undetectable at the EOT and 24 weeks after the EOT.
12 secondary outcomes
The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment
Time frame: Weeks, 2, 4, 8, and 12
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up
Time frame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Time frame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Time frame: Week 4
The Percentage of Participants Achieving an 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 Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Time frame: Week 60
The Percentage of Participants With Viral Breakthrough
Time frame: EOT (up to Week 48)
The Percentage of Participants With Viral Relapse
Time frame: Up to Week 72
The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT)
Time frame: EOT (up to Week 48)
Plasma Concentrations of TMC435
Time frame: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Time frame: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 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 25164700Scott J, Rosa K, Fu M, Cerri K, Peeters M, Beumont M, Zeuzem S, Evon DM, Gilles L. Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection. BMC Infect Dis. 2014 Aug 26;14:465. doi: 10.1186/1471-2334-14-465.
- Derived from this study: PubMed 24184810Zeuzem S, Berg T, Gane E, Ferenci P, Foster GR, Fried MW, Hezode C, Hirschfield GM, Jacobson I, Nikitin I, Pockros PJ, Poordad F, Scott J, Lenz O, Peeters M, Sekar V, De Smedt G, Sinha R, Beumont-Mauviel M. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology. 2014 Feb;146(2):430-41.e6. doi: 10.1053/j.gastro.2013.10.058. Epub 2013 Nov 1.
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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.
Tibotec Pharmaceuticals, Ireland Clinical Trial study director
Tibotec Pharmaceuticals, Ireland
78 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TMC435, Peg-IFN-alfa-2a (P) and Ribavirin (R) in people with Hepatitis C, run by Tibotec Pharmaceuticals, Ireland at 78 sites in 14 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 4 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 9 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in United States, Australia, Germany, Israel, Belgium and 9 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 6 Feb 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 at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24) (time frame: Week 72). 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 NCT00980330, which also lists 3 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 9 Jun 2014.