A Study to Assess the Safety, Tolerability and Efficacy of TMC435 Along With Pegylated Interferon Alpha-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Patients Co-infected With Human Immunodeficiency Virus-Type 1

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01479868
• Collaborator: (none)
• Enrollment: 109
• Locations: 32
• Arm: 1
• Duration (Months): 22
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in hepatitis C virus genotype-1 infected subjects, co-infected with human immunodeficiency virus-type 1, and to evaluate the number of patients with sustained virologic response (SVR) at 12 weeks after the planned end of treatment.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus Genotype-1	Drug: TMC435; Drug: Pegylated interferon alpha-2a; Drug: Ribavirin	Phase 3

Detailed Description

This is an open-label (all the people know the identity of the intervention), single arm (study will be conducted in a single group) clinical study, to evaluate the safety, tolerability and efficacy of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in adult chronic hepatitis C (CHC) genotype-1 infected patients who are co-infected with human immunodeficiency virus-type 1 (HIV-1). The study consists of 3 phases, screening phase (Week -6), treatment phase, and a follow-up phase (up to 24 weeks). In the treatment phase, patients will be classified based on their experience with previous hepatitis C virus (HCV) treatment as follows: 1) HCV treatment-naive (patients who never received medication for the treatment of HCV); 2) prior HCV relapsers (patients who received at least 24 weeks of a PegIFNα-2a and RBV-based therapy and relapsed within 1 year after the last medication intake); and 3) prior HCV non-responders (can be further classified as, null responders: patients having at least 1 prior documented course of PegIFNα-2a and RBV therapy for at least 12 consecutive weeks; or partial responders: patients having at least 20 consecutive weeks which has not been discontinued due to intolerability to PegIFNα-2a and RBV therapy). All patients will receive TMC435 once daily along with PegIFNα-2a and RBV for 12 weeks. Patients who are continuing treatment only with PegIFNα-2a and RBV will follow until 24 or 48 weeks. Pharmacokinetics will be measured after collection of blood samples. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examinations, and specific toxicities will be performed throughout the study. The total duration of treatment is approximately of 24 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of TMC435 Plus PegIFNα-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Subjects Who Are Co-infected With Human Immunodeficiency Virus Type 1 (HIV-1)
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMC435 + pegylated interferon alpha-2a + ribavirin Patients will be administered TMC435 150 mg along with pegylated interferon alpha-2a 180 microgram and ribavirin 1000 or 1200 mg for 12 weeks. Pegylated interferon alpha-2a and ribavirin will only be continued until 24 to 48 weeks.	Drug: TMC435; TMC435 150 mg will be administered once daily for 12 weeks along with peginterferon alpha-2a and ribavirin.; Drug: Pegylated interferon alpha-2a; Pegylated interferon alpha-2a 180 microgram will be administered as subcutaneous injection of 0.5 mL until 24 to 48 weeks.; Drug: Ribavirin; Ribavirin 1000 or 1200 mg twice daily will be administered each day until 24 to 48 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) [12 weeks after end of treatment (Week 24 or 48)]

   The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 12 Weeks after end of treatment.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) [24 weeks after end of treatment (Week 24 or 48)]

   The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 24 weeks after end of treatment.

2. Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable [Week 4, 12, 24, 36, and 48]

   Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed.

3. Percentage of Participants With On-treatment Failure [Week 1 to 48]

   Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels.

4. Percentage of Participants With Viral Breakthrough [Week 1 to 48]

   Confirmed increase of more than 1 log10 IU per mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of more than 100 IU per mL in participants whose HCV RNA levels had previously been below the limit of quantification (less than 25 IU per mL detectable) or undetectable (less than 25 IU per mL undetectable), while on study therapy.

5. Percentage of Participants With Viral Relapse [Week 1 to 72]

   Participants were considered to have a viral relapse when, at actual end of treatment, HCV RNA levels were less than 25 IU per mL undetectable; and during the follow-up period, HCV RNA levels were more than or equal to 25 IU per mL.

6. Percentage of Participants With Normalized Alanine Aminotransferase Levels [Baseline up to Week 72]

   Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline.

7. Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure [Baseline to Week 72.]

   Participants had confirmed HIV virologic failure if HIV viral load values were greater than or equal to 50 or 200 copies/mL among those who previously had less than 50 copies/mL.

8. Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load [Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72]

9. Mean Change From Baseline in CD4+ Cell Count [Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72]

10. Change From Baseline in CD4+ Cell Count in Percentage [Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72]

11. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [Week 1 to Week 72]

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 126 that were absent before treatment or that worsened relative to pre-treatment state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A liver biopsy required within 3 years prior to screening unless the patient has a contraindication for a liver biopsy

• Patients with bridging fibrosis or cirrhosis and without a liver biopsy result within 2 years prior screening must have an ultrasound taken within 2 months prior to the screening visit or during screening with no findings suspicious for hepatocellular carcinoma (HCC)

• Genotype-1 hepatitis C virus (HCV) infection

• Plasma HCV ribonucleic acid (RNA) of more than 10,000 IU per mL

• Documented human immunodeficiency virus-type 1 (HIV-1) infection at least 6 months prior to screening

Exclusion Criteria:

• Patient showing evidence of hepatic decompensation (ie, history or current evidence of ascites, bleeding varices or hepatic encephalopathy, albumin serum concentration less than 3.3 gm per dL, prolonged prothrombin time [PT] expressed as international normalized ratio [INR] more than 1.5)

• Any liver disease of non-HCV etiology

• Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)

• An acute HIV-1 infection; or HIV-2 infection

• Change in antiretroviral (ARV) regimen within the last 4 weeks prior screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States
2		Washington	District of Columbia	United States
3		Orlando	Florida	United States
4		Atlanta	Georgia	United States
5		Chicago	Illinois	United States
6		Newark	New Jersey	United States
7		Albany	New York	United States
8		New York	New York	United States
9		Dallas	Texas	United States
10		Houston	Texas	United States
11		Toronto	Ontario	Canada
12		Montreal	Quebec	Canada
13		Lyon		France
14		Montpellier Cedex 5		France
15		Nantes		France
16		Paris		France
17		Berlin		Germany
18		Bonn		Germany
19		Düsseldorf		Germany
20		Frankfurt		Germany
21		Freiburg		Germany
22		Hamburg		Germany
23		Köln		Germany
24		Amadora		Portugal
25		Lisboa		Portugal
26		Porto		Portugal
27		San Juan		Puerto Rico
28		Badalona		Spain
29		Elche		Spain
30		Madrid		Spain
31		Brighton		United Kingdom
32		London		United Kingdom

Sponsors and Collaborators

• Janssen R&D Ireland

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen R&D Ireland
• ClinicalTrials.gov Identifier: NCT01479868
• Other Study ID Numbers: CR018334; TMC435-TiDP16-C212; NCT01727323
• First Posted: Nov 28, 2011
• Last Update Posted: Oct 29, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Janssen R&D Ireland: Hepatitis C virus genotype-1; Human immunodeficiency virus-type 1; HCV-1; HIV-1; TMC435; Pegylated interferon alpha-2a; PegIFNα-2a; Pegasys; Ribavirin; RBV; Copegus
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Acquired Immunodeficiency Syndrome; HIV Infections; Hepatitis; Immunologic Deficiency Syndromes; Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a; Simeprevir

Study Results

Participant Flow

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Period Title: Overall Study
STARTED	106
COMPLETED	97
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Overall Participants	106
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48
Sex: Female, Male (Count of Participants)
Female	16 15.1%
Male	90 84.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)
Description	The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 12 Weeks after end of treatment.
Time Frame	12 weeks after end of treatment (Week 24 or 48)

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population included all participants who received at least 1 dose of study drug.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	106
Number [percentage of participants]	73.6 69.4%

2. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)
Description	The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 24 weeks after end of treatment.
Time Frame	24 weeks after end of treatment (Week 24 or 48)

Outcome Measure Data

Analysis Population Description

The ITT population included all perticipants who had at least 1 dose of study drug.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	106
Number [percentage of participants]	72.6 68.5%

3. Secondary Outcome

Title	Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable
Description	Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed.
Time Frame	Week 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who had at least 1 dose of study drug. Here, "N" (number of participants analyzed) is the number of participants analyzed for this outcome measure, "n" is the number of participants analyzed for this outcome measure at specific time points.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	105
Week 4: < 25 IU/mL HCV-RNA undet. (n=105)	65.7 62%
Week 4:< 25 IU/mL HCV-RNA det./undet. (n=105)	88.6 83.6%
Week 12:< 25 IU/mL HCV-RNA undet. (n=97)	94.8 89.4%
Week 12:< 25 IU/mL HCV-RNA det./undet. (n=97)	97.9 92.4%
Week 24:< 25 IU/mL HCV-RNA undet. (n=90)	90.0 84.9%
Week 24:< 25 IU/mL HCV-RNA det./undet. (n=90)	93.3 88%
Week 48:< 25 IU/mL HCV-RNA undet. (n=20)	100 94.3%
Week 48:< 25 IU/mL HCV-RNA det./undet. (n=20)	100 94.3%

4. Secondary Outcome

Title	Percentage of Participants With On-treatment Failure
Description	Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels.
Time Frame	Week 1 to 48

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who received at least 1 dose of study drug.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	106
Number [percentage of participants]	17 16%

5. Secondary Outcome

Title	Percentage of Participants With Viral Breakthrough
Description	Confirmed increase of more than 1 log10 IU per mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of more than 100 IU per mL in participants whose HCV RNA levels had previously been below the limit of quantification (less than 25 IU per mL detectable) or undetectable (less than 25 IU per mL undetectable), while on study therapy.
Time Frame	Week 1 to 48

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who received at least 1 dose of study drug.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	105
Number [percentage of participants]	11.4 10.8%

6. Secondary Outcome

Title	Percentage of Participants With Viral Relapse
Description	Participants were considered to have a viral relapse when, at actual end of treatment, HCV RNA levels were less than 25 IU per mL undetectable; and during the follow-up period, HCV RNA levels were more than or equal to 25 IU per mL.
Time Frame	Week 1 to 72

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who received at least 1 dose of study drug. Here, "N" (number of participants analyzed) is the number of participants analyzed for this outcome measure.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	87
Number [percentage of participants]	10.3 9.7%

7. Secondary Outcome

Title	Percentage of Participants With Normalized Alanine Aminotransferase Levels
Description	Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline.
Time Frame	Baseline up to Week 72

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who received at least 1 dose of study drug. Here "N" signifies participants evaluable for this measure.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	65
Number [percentage of participants]	81.5 76.9%

8. Secondary Outcome

Title	Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure
Description	Participants had confirmed HIV virologic failure if HIV viral load values were greater than or equal to 50 or 200 copies/mL among those who previously had less than 50 copies/mL.
Time Frame	Baseline to Week 72.

Outcome Measure Data

Analysis Population Description

Participants who received potent anti-HIV treatment with a combination of more than 3 anti-antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	93
Greater than or equal to 50 copies/mL	5.4 5.1%
Greater than or equal to 200 copies/mL	2.2 2.1%

9. Secondary Outcome

Title	Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load
Time Frame	Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72

Outcome Measure Data

Analysis Population Description

Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed. Here "n" signifies participants evaluable for this measure at specified time point.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	93
Baseline (n=93)	1.3726 (0.25796)
Change at Week 2 (n=91)	-0.0724 (0.23857)
Change at Week 4 (n=93)	-0.0704 (0.25817)
Change at Week 8 (n=92)	-0.0442 (0.40974)
Change at Week 12 (n=90)	-0.0655 (0.30510)
Change at Week 16 (n=88)	-0.0829 (0.23986)
Change at Week 20 (n=86)	-0.0847 (0.25111)
Change at Week 24 (n=88)	-0.0689 (0.24785)
Change at Week 28 (n=82)	-0.0564 (0.26319)
Change at Week 36 (n=85)	0.0004 (0.24395)
Change at Week 42 (n=35)	-0.0623 (0.29365)
Change at Week 48 (n=79)	-0.0041 (0.36177)
Change at Week 52 (n=36)	0.0011 (0.20767)
Change at Week 60 (n=40)	-0.0184 (0.20940)
Change at Week 72 (n=38)	-0.0265 (0.18323)
Change at End of study (n=93)	0.0099 (0.33435)

10. Secondary Outcome

Title	Mean Change From Baseline in CD4+ Cell Count
Time Frame	Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72

Outcome Measure Data

Analysis Population Description

Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed. Here, "n" is the number of participants analyzed for this outcome measure at spcific time points.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	93
Baseline (n=93)	640.3 (243.11)
Change at Week 2 (n=89)	-95.0 (190.34)
Change at Week 4 (n=91)	-171.5 (170.67)
Change at Week 8 (n=92)	-244.2 (185.04)
Change at Week 12 (n=91)	-271.7 (194.49)
Change at Week 16 (n=88)	-275.5 (183.96)
Change at Week 20 (n=84)	-283.5 (175.27)
Change at Week 24 (n=89)	-288.8 (202.31)
Change at Week 28 (n=82)	-252.3 (203.45)
Change at Week 36 (n=83)	-198.7 (225.62)
Change at Week 42 (n=33)	-336.8 (240.64)
Change at Week 48 (n=77)	-166.6 (248.25)
Change at Week 52 (n=35)	-202.7 (222.89)
Change at Week 60 (n=40)	-90.6 (189.74)
Change at Week 72 (n=38)	-62.9 (175.61)
Change at End of Study (n=93)	-51.1 (178.20)

11. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count in Percentage
Time Frame	Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72

Outcome Measure Data

Analysis Population Description

Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed. Here, "n" is the number of participants analyzed for this outcome measure at spcific time points.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	93
Baseline (n=93)	31.65 (8.390)
Change at Week 2 (n=89)	0.42 (6.490)
Change at Week 4 (n=91)	2.50 (5.943)
Change at Week 8 (n=92)	3.85 (5.930)
Change at Week 12 (n=91)	3.93 (6.264)
Change at Week 16 (n=88)	5.47 (6.301)
Change at Week 20 (n=84)	5.27 (6.961)
Change at Week 24 (n=89)	5.50 (7.029)
Change at Week 28 (n=82)	3.79 (6.759)
Change at Week 36 (n=83)	2.75 (6.492)
Change at Week 42 (n=33)	6.41 (6.213)
Change at Week 48 (n=77)	2.09 (7.356)
Change at Week 52 (n=35)	3.26 (6.838)
Change at Week 60 (n=40)	0.25 (5.296)
Change at Week 72 (n=38)	0.70 (4.406)
Change at End of study (n=93)	0.13 (6.169)

12. Secondary Outcome

Title	Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 126 that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Week 1 to Week 72

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug.

Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
Measure Participants	106
TEAEs	102 96.2%
TESAEs	6 5.7%

Adverse Events

Time Frame	Week 1 to Week 72
Arm/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
All Cause Mortality
	TMC435 150mg 12Wks PR24/48
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TMC435 150mg 12Wks PR24/48
	Affected / at Risk (%)	# Events
Total	11/106 (10.4%)
Blood and lymphatic system disorders
Anaemia	1/106 (0.9%)
Cardiac disorders
Angina pectoris	1/106 (0.9%)
Gastrointestinal disorders
Anal haemorrhage	1/106 (0.9%)
Colitis	1/106 (0.9%)
General disorders
General physical health deterioration	1/106 (0.9%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/106 (0.9%)
Infections and infestations
Catheter site infection	1/106 (0.9%)
Injury, poisoning and procedural complications
Thoracic vertebral fracture	1/106 (0.9%)
Investigations
Aspartate aminotransferase increased	1/106 (0.9%)
Metabolism and nutrition disorders
Malnutrition	1/106 (0.9%)
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis	1/106 (0.9%)
Intervertebral disc protrusion	1/106 (0.9%)
Psychiatric disorders
Mental status changes	1/106 (0.9%)
Psychotic disorder	1/106 (0.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/106 (1.9%)
Pneumothorax	1/106 (0.9%)
Other (Not Including Serious) Adverse Events
	TMC435 150mg 12Wks PR24/48
	Affected / at Risk (%)	# Events
Total	103/106 (97.2%)
Blood and lymphatic system disorders
Neutropenia	33/106 (31.1%)
Anaemia	30/106 (28.3%)
Thrombocytopenia	6/106 (5.7%)
Gastrointestinal disorders
Nausea	31/106 (29.2%)
Diarrhoea	25/106 (23.6%)
Vomiting	14/106 (13.2%)
Constipation	12/106 (11.3%)
General disorders
Fatigue	48/106 (45.3%)
Influenza like illness	25/106 (23.6%)
Asthenia	24/106 (22.6%)
Pyrexia	12/106 (11.3%)
Chills	9/106 (8.5%)
Injection site reaction	8/106 (7.5%)
Pain	7/106 (6.6%)
Injection site erythema	6/106 (5.7%)
Infections and infestations
Nasopharyngitis	7/106 (6.6%)
Upper respiratory tract infection	7/106 (6.6%)
Investigations
Weight decreased	13/106 (12.3%)
Neutrophil count decreased	6/106 (5.7%)
Metabolism and nutrition disorders
Decreased appetite	21/106 (19.8%)
Musculoskeletal and connective tissue disorders
Myalgia	17/106 (16%)
Arthralgia	15/106 (14.2%)
Back pain	8/106 (7.5%)
Pain in extremity	6/106 (5.7%)
Nervous system disorders
Headache	35/106 (33%)
Dizziness	13/106 (12.3%)
Psychiatric disorders
Insomnia	27/106 (25.5%)
Mood altered	20/106 (18.9%)
Depression	19/106 (17.9%)
Anxiety	13/106 (12.3%)
Sleep disorder	6/106 (5.7%)
Respiratory, thoracic and mediastinal disorders
Cough	11/106 (10.4%)
Dyspnoea	10/106 (9.4%)
Oropharyngeal pain	9/106 (8.5%)
Skin and subcutaneous tissue disorders
Pruritus	19/106 (17.9%)
Dry skin	16/106 (15.1%)
Eczema	8/106 (7.5%)
Alopecia	7/106 (6.6%)
Rash	7/106 (6.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.