Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01281839




Trial ID
NCT01281839
Ethics application status
Date submitted
7/01/2011
Date registered
21/01/2011
Date last updated
26/03/2014

Titles & IDs
Public title
An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy
Scientific 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 a-2a and Ribavirin in Hepatitis C, Genotype 1 Infected Subjects Who Relapsed After Previous Interferon-based Therapy
Secondary ID [1] 0 0
TMC435HPC3007
Secondary ID [2] 0 0
CR017371
Universal Trial Number (UTN)
Trial acronym
PROMISE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TMC435
Treatment: Drugs - Placebo
Treatment: Drugs - Peginterferon alpha-2a (PegIFN alpha-2a)
Treatment: Drugs - Ribavirin (RBV)

Experimental: TMC435 - TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks

Placebo Comparator: Placebo - Placebo 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks


Treatment: Drugs: TMC435
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks

Treatment: Drugs: Placebo
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks

Treatment: Drugs: Peginterferon alpha-2a (PegIFN alpha-2a)
One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks.

Treatment: Drugs: Ribavirin (RBV)
200-mg tablets of RBV (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 36 or Week 60
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 72
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Week 48 or Week 72
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Week 28 or Week 52
Secondary outcome [4] 0 0
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) - The table below shows change from baseline in log10 HCV RNA levels.
Timepoint [4] 0 0
Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Week 4
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Week 12
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Week 12
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Week 4 and Week 12
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Week 4
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Week 4
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Week 12
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Week 12
Secondary outcome [15] 0 0
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).
Timepoint [15] 0 0
Up to Week 48
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
Up to Week 72
Secondary outcome [17] 0 0
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 PegIFNa-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 PegIFNa-2a and RBV treatment for 48 weeks.
Timepoint [17] 0 0
Week 24
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
Week 48
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
Up to Week 48
Secondary outcome [20] 0 0
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.
Timepoint [20] 0 0
Up to Week 48
Secondary outcome [21] 0 0
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.
Timepoint [21] 0 0
Up to Week 48
Secondary outcome [22] 0 0
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.
Timepoint [22] 0 0
Up to Week 48
Secondary outcome [23] 0 0
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).
Timepoint [23] 0 0
Up to Week 48
Secondary outcome [24] 0 0
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.
Timepoint [24] 0 0
Up to Week 72
Secondary outcome [25] 0 0
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.
Timepoint [25] 0 0
Up to Week 48
Secondary outcome [26] 0 0
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels - The table below shows the median time to normalization of ALT levels.
Timepoint [26] 0 0
Up to Week 48
Secondary outcome [27] 0 0
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.
Timepoint [27] 0 0
From the time of administration up to 24 hours after dosing through Week 12
Secondary outcome [28] 0 0
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.
Timepoint [28] 0 0
Before administration of TMC435 through Week 12
Secondary outcome [29] 0 0
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.
Timepoint [29] 0 0
From the time of administration through Week 12

Eligibility
Key inclusion criteria
- 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)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Kingswood
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Sydney
Recruitment hospital [5] 0 0
- Woolloongabba N/A
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Kingswood
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment postcode(s) [5] 0 0
- Woolloongabba N/A
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Mississippi
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Austria
State/province [10] 0 0
Wien
Country [11] 0 0
Belgium
State/province [11] 0 0
Antwerpen
Country [12] 0 0
Belgium
State/province [12] 0 0
Brugge
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussels
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussel
Country [15] 0 0
Belgium
State/province [15] 0 0
Gent
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
France
State/province [20] 0 0
Creteil N/A
Country [21] 0 0
France
State/province [21] 0 0
Grenoble
Country [22] 0 0
France
State/province [22] 0 0
Lyon
Country [23] 0 0
France
State/province [23] 0 0
Nice N/A
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 12
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
France
State/province [26] 0 0
Rennes Cedex
Country [27] 0 0
France
State/province [27] 0 0
Vandoeuvre Les Nancy
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Düsseldorf
Country [30] 0 0
Germany
State/province [30] 0 0
Frankfurt
Country [31] 0 0
Germany
State/province [31] 0 0
Freiburg
Country [32] 0 0
Germany
State/province [32] 0 0
Halle (Saale)
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Germany
State/province [34] 0 0
Kiel
Country [35] 0 0
Germany
State/province [35] 0 0
Leipzig
Country [36] 0 0
Germany
State/province [36] 0 0
Munchen
Country [37] 0 0
Germany
State/province [37] 0 0
Würzburg
Country [38] 0 0
New Zealand
State/province [38] 0 0
Auckland
Country [39] 0 0
New Zealand
State/province [39] 0 0
Christchurch
Country [40] 0 0
New Zealand
State/province [40] 0 0
Hamilton
Country [41] 0 0
Poland
State/province [41] 0 0
Bialystok
Country [42] 0 0
Poland
State/province [42] 0 0
Bydgoszcz
Country [43] 0 0
Poland
State/province [43] 0 0
Czeladz
Country [44] 0 0
Poland
State/province [44] 0 0
Kielce
Country [45] 0 0
Poland
State/province [45] 0 0
Krakow
Country [46] 0 0
Poland
State/province [46] 0 0
Warszawa
Country [47] 0 0
Puerto Rico
State/province [47] 0 0
Ponce Pr
Country [48] 0 0
Puerto Rico
State/province [48] 0 0
San Juan
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Moscow
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Saint-Petersburg
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Samara
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Smolensk
Country [53] 0 0
Russian Federation
State/province [53] 0 0
St Petersburg
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Stavropol
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Madrid
Country [57] 0 0
Spain
State/province [57] 0 0
Sevilla N/A
Country [58] 0 0
Spain
State/province [58] 0 0
Valencia
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Birmingham
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Derby
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Glasgow
Country [62] 0 0
United Kingdom
State/province [62] 0 0
London
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen R&D Ireland
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT01281839
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen R&D Ireland Clinical Trial
Address 0 0
Janssen R&D Ireland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries