Clinical Trial Results:
A Phase 3, Multicentre, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of a 12-Week Regimen of Simeprevir in Combination with Sofosbuvir in Treatment naïve or -Experienced Subjects with Chronic Genotype 4 Hepatitis C Virus Infection
|
Summary
|
|
EudraCT number |
2014-003446-27 |
Trial protocol |
ES |
Global end of trial date |
23 Dec 2015
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
10 Nov 2016
|
First version publication date |
10 Nov 2016
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
TMC435HPC3021
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02250807 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Janssen R&D Ireland
|
||
Sponsor organisation address |
Turnhoutseweg 30, 2340 Beerse, Belgium,
|
||
Public contact |
Global Clinical Operations, Janssen R&D Ireland, ClinicalTrialsEU@its.jnj.com
|
||
Scientific contact |
Global Clinical Operations, Janssen R&D Ireland, ClinicalTrialsEU@its.jnj.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
23 Dec 2015
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
23 Dec 2015
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objective of this study was to show superiority of simeprevir (SMV) 150 milligram (mg) once daily in combination with sofosbuvir (SOF) 400 mg once daily for 12 weeks versus a historical control, with respect to the proportion of participants with sustained virologic response 12 (SVR12) in the overall population.
|
||
Protection of trial subjects |
Safety evaluations for this study included the monitoring of adverse events (AEs); laboratory tests (hematology, urinalysis and serum chemistry); vital sign measurements and physical examinations.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Jan 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 40
|
||
Worldwide total number of subjects |
40
|
||
EEA total number of subjects |
40
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
38
|
||
From 65 to 84 years |
2
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
- | ||||||
|
Pre-assignment
|
|||||||
Screening details |
The study was conducted from 7 January 2015 to 23 December 2015. 40 participants were enrolled in the study and received treatment. | ||||||
|
Period 1
|
|||||||
Period 1 title |
Overall Study (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
|
||||||
Blinding used |
Not blinded | ||||||
|
Arms
|
|||||||
|
Arm title
|
SMV+SOF 12 Weeks | ||||||
Arm description |
Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Simeprevir
|
||||||
Investigational medicinal product code |
|||||||
Other name |
|||||||
Pharmaceutical forms |
Capsule
|
||||||
Routes of administration |
Oral use
|
||||||
Dosage and administration details |
Participants received oral capsule of SMV 150 mg once a day from Day 1 through Week 12.
|
||||||
Investigational medicinal product name |
Sofosbuvir
|
||||||
Investigational medicinal product code |
|||||||
Other name |
|||||||
Pharmaceutical forms |
Tablet
|
||||||
Routes of administration |
Oral use
|
||||||
Dosage and administration details |
Subjects received oral tablet of SOF 400 mg, once a day from Day 1 through Week 12.
|
||||||
|
|||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SMV+SOF 12 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12. | ||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
SMV+SOF 12 Weeks
|
||
Reporting group description |
Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12. | ||
|
|||||||||
End point title |
Percentage of Participants With Sustained Virologic Response 12 Weeks after End of Treatment (EOT) (SVR12) [1] | ||||||||
End point description |
SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT. Intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
12 weeks after EOT
|
||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive Statistical analysis was performed for the outcome measure. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4) | ||||||||
End point description |
SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT. ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
4 weeks after EOT
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24) | ||||||||
End point description |
Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the actual end of treatment [EOT]) the following condition has been met: HCV RNA < lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable. ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
At 24 weeks after EOT
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | ||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of participants with HCV RNA less than (<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed. ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
|
||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 2, 3, 4, 12 and EOT
|
||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
|
|||||||||
End point title |
Percentage of Participants With On-treatment Failure | ||||||||
End point description |
Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., <LLOQ detectable or >=LLOQ. ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Through 12 weeks (EOT)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With Viral Breakthrough | ||||||||
End point description |
Participants with confirmed >1.0 log10 increase in HCV RNA from nadir whilst on study therapy or confirmed HCV RNA >100 IU/mL whilst on study therapy in participants who had previously achieved HCV RNA <LLOQ. ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to follow-up Week 24
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With Viral Relapse | ||||||||
End point description |
Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (<)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (>=)LLOQ. ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to follow-up week 24
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to EOT (Week 12)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SMV+SOF 12 Wks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Apr 2015 |
The amendment 1 was reported as an “urgent safety measure” to disallow the use of amiodarone from Screening onwards until the end of the treatment period to protect the safety of the participants. On 24 March 2015, the United States Food and Drug Administration (FDA) issued warnings on the risk of bradycardia and cardiac arrest when the antiarrhythmic drug amiodarone is used together with sofosbuvir (SOF) or the fixed-dose combination SOF/ledipasvir in combination with another direct-acting antiviral (DAA) for the treatment of hepatitis C virus (HCV) infection. The FDA recommended that health care professionals should not prescribe SOF combined with another DAA, such as simeprevir (SMV), with amiodarone. Therefore, the sponsor considered it necessary to disallow the co-administration of amiodarone while participants were treated with the combination of SMV+SOF in this study, to avoid the risk of potential drug interactions. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
