3-year Follow-up Study in Patients Previously Treated With TMC435-Containing Regimen for the Treatment of Hepatitis C Virus Infection

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01349465
• Collaborator: (none)
• Enrollment: 249
• Locations: 49
• Arms: 2
• Actual Duration (Months): 54.1
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate durability of SVR in chronic HCV patients who achieved SVR in the previous study with TMC435-containing regimen and time for resistance associated mutations to return to baseline in chronic HCV patients who did not achieve SVR in the previous study with TMC435-containing regimen.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: No treatment	Phase 3

Detailed Description

This is a 3-year follow-up study in patients who completed the last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study in which they received TMC435, in combination with pegylated interferon and ribavirin, for the treatment of hepatitis C infection. The entire study duration for each patients will be approximately 36 months. The medical follow-up of the patients will be performed according to the local standard of care. This study will evaluate the levels of hepatitis C virus in the blood circulation, as well as safety and alpha-fetoprotein testing and the change in sequence of HCV NS3/4A region over time in patients with confirmed detectable HCV RNA at last post-therapy follow-up visit of the previous TMC435 study. In this study the development of liver disease progression will also be assessed. No medication will be administered in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 249 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Prospective 3-Year Follow-up Study in Subjects Previously Treated in a Phase IIb or Phase III Study With a TMC435-Containing Regimen for the Treatment of Hepatitis C Virus (HCV) Infection
• Actual Study Start Date: Jul 4, 2011
• Actual Primary Completion Date: Jan 5, 2016
• Actual Study Completion Date: Jan 5, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Group 1: TMC 435 - Patients With SVR at LPVPS Patients with sustained virologic response (SVR) who completed last post-therapy follow-up visit of the previous study (LPVPS) [Phase IIb or Phase III] in which they received a TMC435-containing regimen for the treatment of HCV infection.	Drug: No treatment; No treatment was given to patients during this study as this is a follow-up study of previous Phase IIb or Phase III in which they received a TMC435-containing regimen.
Other: Group 2: TMC 435 - Patients With No SVR at LPVPS Patients with no sustained virologic response (SVR) who completed last post-therapy follow-up visit of the previous study (LPVPS) [Phase IIb or Phase III] in which they received a TMC435-containing regimen for the treatment of HCV infection.	Drug: No treatment; No treatment was given to patients during this study as this is a follow-up study of previous Phase IIb or Phase III in which they received a TMC435-containing regimen.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Maintaining SVR at the Last Available Visit [Last Available Visit (Month 36 for subjects completing the study)]

   The SVR rate is the proportion (%) of participants with HCV RNA less than (<) 25 International Units/milliliter (IU/mL).

2. Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study [Baseline and Month 36]

   Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.

3. Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study [Baseline and Month 36]

   Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.

4. Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study [Baseline and Month 36]

   Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.

Secondary Outcome Measures

1. Percentage of Participants With Late Viral Relapse [End of study (at month 36)]

   Relapse at any time after the LPVPS until the last individual visit of this study. All participants maintained SVR until the last available visit. No late viral relapse was therefore observed.

2. Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [End of study (at month 36)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have previously participated in a Phase IIb or Phase III study

• Must have received at least one dose of TMC435 in that study

• Has completed the last post-therapy follow-up visit of the previous (LPVPS) study

Exclusion Criteria:

• Must be currently enrolled or plan to enroll in another study with an investigational drug or invasive investigational medical device

• Have received antiviral or immunomodulating treatment, including therapeutic vaccines, for hepatitis C virus (HCV) between LPVPS and the screening visit of present study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bakersfield	California	United States
2		La Jolla	California	United States
3		Los Angeles	California	United States
4		Jacksonville	Florida	United States
5		Orlando	Florida	United States
6		Chicago	Illinois	United States
7		New Orleans	Louisiana	United States
8		Saint Paul	Minnesota	United States
9		Tupelo	Mississippi	United States
10		Chapel Hill	North Carolina	United States
11		Cincinnati	Ohio	United States
12		San Antonio	Texas	United States
13		Antwerpen		Belgium
14		Brugge		Belgium
15		Brussels		Belgium
16		Gent		Belgium
17		Leuven		Belgium
18		Calgary	Alberta	Canada
19		Ottawa	Ontario	Canada
20		Toronto	Ontario	Canada
21		Montreal	Quebec	Canada
22		Montreal		Canada
23		Creteil		France
24		Grenoble		France
25		Lyon		France
26		Nice N/A		France
27		Paris		France
28		Vandoeuvre-Les-Nancy		France
29		Berlin		Germany
30		Düsseldorf		Germany
31		Frankfurt A. M.		Germany
32		Freiburg		Germany
33		Hamburg		Germany
34		Hannover		Germany
35		Kiel		Germany
36		Köln		Germany
37		Würzburg		Germany
38		Bialystok		Poland
39		Bydgoszcz		Poland
40		Czeladz		Poland
41		Myslowice		Poland
42		Warszawa		Poland
43		Moscow		Russian Federation
44		Nizhny Novgorod		Russian Federation
45		Saint-Petersburg		Russian Federation
46		Samara		Russian Federation
47		Smolensk		Russian Federation
48		St Petersburg		Russian Federation
49		Stavropol		Russian Federation

Sponsors and Collaborators

• Janssen R&D Ireland

Investigators

• Study Director: Janssen R&D Ireland Clinical Trial, Janssen R&D Ireland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen R&D Ireland
• ClinicalTrials.gov Identifier: NCT01349465
• Other Study ID Numbers: CR017365; TMC435HPC3002; 2010-019843-20
• First Posted: May 6, 2011
• Last Update Posted: Apr 10, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Janssen R&D Ireland: Hepatitis C; Hepatitis; TMC435; Liver disease; Virus Infection
• Additional relevant MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis

Study Results

Participant Flow

Pre-assignment Detail	In total 250 participants were screened and among those 249 were enrolled into the study (200 participants with SVR and 49 participants with no SVR).

Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study	No SVR at Last Post-Therapy Follow-up Visit of Previous Study
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.	Participants with no sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.
Period Title: Overall Study
STARTED	200	49
COMPLETED	182	27
NOT COMPLETED	18	22

Baseline Characteristics

Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study	No SVR at Last Post-Therapy Follow-up Visit of Previous Study	Total
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.	Participants with no sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.	Total of all reporting groups
Overall Participants	200	49	249
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	56	53
Sex: Female, Male (Count of Participants)
Female	78 39%	17 34.7%	95 38.2%
Male	122 61%	32 65.3%	154 61.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Maintaining SVR at the Last Available Visit
Description	The SVR rate is the proportion (%) of participants with HCV RNA less than (<) 25 International Units/milliliter (IU/mL).
Time Frame	Last Available Visit (Month 36 for subjects completing the study)

Outcome Measure Data

Analysis Population Description

All participants with SVR at LPVPS were included in the population analysis set.

Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.
Measure Participants	200
Number (95% Confidence Interval) [Percentage of participants]	100 50%

2. Primary Outcome

Title	Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study
Description	Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

"N" signifies number of participants with no SVR at LPVPS and with available sequence data. "n" defines the number of participants analyzed at specified time point.

Arm/Group Title	No SVR at Last Post-Therapy Follow-up Visit of Previous Study
Arm/Group Description	Participants with no sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.
Measure Participants	48
NEM Return to Baseline at EOS (n=5)	0.0 0%
NEM Change to New Profile at EOS (n=5)	0.0 0%
AEM Return to Baseline at EOS (n=43)	86.0 43%
AEM Change to New Profile at EOS (n=43)	7.0 3.5%

3. Secondary Outcome

Title	Percentage of Participants With Late Viral Relapse
Description	Relapse at any time after the LPVPS until the last individual visit of this study. All participants maintained SVR until the last available visit. No late viral relapse was therefore observed.
Time Frame	End of study (at month 36)

Outcome Measure Data

Analysis Population Description

Late viral relapse was evaluated in all enrolled participants with SVR at LPVPS.

Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.
Measure Participants	200
Number [percentage of participants]	0 0%

4. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame	End of study (at month 36)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study	No SVR at Last Post-Therapy Follow-up Visit of Previous Study
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.	Participants with no sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.
Measure Participants	200	49
Adverse Events (AE)	4 2%	1 2%
Serious Adverse Events (SAE)	10 5%	0 0%

5. Primary Outcome

Title	Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study
Description	Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

"N" signifies number of particpants with no SVR at LPVPS and with available sequence data. "n" defines the number of participants analyzed at specified time point.

Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.
Measure Participants	10
NEM Return to Baseline at EOS (n=1)	0.0 0%
NEM Change to New Profile at EOS (n=1)	0.0 0%
AEM Return to Baseline at EOS (n=9)	88.9 44.5%
AEM Change to New Profile at EOS (n=9)	0.0 0%

6. Primary Outcome

Title	Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study
Description	Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

"N" signifies number of particpants with no SVR at LPVPS and with available sequence data. "n" defines the number of participants analyzed at specified time point.

Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.
Measure Participants	38
NEM Return to Baseline at EOS (n=4)	0.0
NEM Change to New Profile at EOS (n=4)	0.0
AEM Return to Baseline at EOS (n=34)	85.3
AEM Change to New Profile at EOS (n=34)	8.8

Adverse Events

Time Frame	End of study (36 Months)
Adverse Event Reporting Description	Only Adverse Events associated with a study procedure or the use of any J&J medication were collected from signing of the Informed Consent Form onwards until the last study visit and classified according to the existing procedures. If during the study, hepatocellular carcinoma (HCC) was diagnosed, it should be reported as an AE.
Arm/Group Title	SVR at Last Post-Therapy Follow-up Visit of Previous Study		No SVR at Last Post-Therapy Follow-up Visit of Previous Study		Total
Arm/Group Description	Participants with sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.		Participants with no sustained virologic response (SVR) at last post-therapy follow-up visit of the previous Phase IIb [NCT00882908, NCT00980330] or Phase III [NCT01289782, NCT01290679, NCT01281839] study.		All Enrolled Subjects
All Cause Mortality
	SVR at Last Post-Therapy Follow-up Visit of Previous Study		No SVR at Last Post-Therapy Follow-up Visit of Previous Study		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SVR at Last Post-Therapy Follow-up Visit of Previous Study		No SVR at Last Post-Therapy Follow-up Visit of Previous Study		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/200 (5%)		0/49 (0%)		10/249 (4%)
Cardiac disorders
Myocardial infarction	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Gastrointestinal disorders
Abdominal pain upper	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Ascites	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Diarrhoea	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Pancreatitis	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Pancreatitis acute	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Varices oesophageal	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
General disorders
Chest pain	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
General physical health deterioration	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Hepatobiliary disorders
Biliary colic	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Cholangitis	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Hydrocholecystis	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant	3/200 (1.5%)		0/49 (0%)		3/249 (1.2%)
Colon cancer	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Gastrointestinal tract adenoma	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Pancreatic carcinoma	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Nervous system disorders
Cerebrovascular accident	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Other (Not Including Serious) Adverse Events
	SVR at Last Post-Therapy Follow-up Visit of Previous Study		No SVR at Last Post-Therapy Follow-up Visit of Previous Study		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/200 (2%)		1/49 (2%)		5/249 (2%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Hepatobiliary disorders
Bile duct stone	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Cholecystitis chronic	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Investigations
Alpha 1 foetoprotein increased	0/200 (0%)		1/49 (2%)		1/249 (0.4%)
Nervous system disorders
Dysarthria	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)
Hemiparesis	1/200 (0.5%)		0/49 (0%)		1/249 (0.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.