PARTNER: Infliximab Treatment Along With Pegylated Interferon and Ribavirin in the Treatment of Hepatitis C

• Sponsor: Nizar Zein (Other)
• Overall Status: Completed
• CT.gov ID: NCT00512278
• Collaborator: Centocor, Inc. (Industry)
• Enrollment: 146
• Locations: 7
• Arms: 2
• Duration (Months): 58
• Patients Per Site: 20.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The aim of the study is to investigate in subjects receiving their first course of peg-interferon α-2b plus ribavirin therapy for chronic HCV infection

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Infliximab; Drug: Placebo	Phase 2

Detailed Description

The aim of the study is to investigate in subjects receiving their first course of peg-interferon α-2b plus ribavirin therapy for chronic HCV infection (genotype 1) whether the addition of infliximab to a standard regimen of pegylated interferon α-2b in combination with ribavirin:

• increases the proportion of subjects attaining a sustained virological response SVR (undetectable blood Hepatitis C viral load 6 months after treatment)

• improves the safety profile compared to the same regimen without infliximab

Study Design

• Study Type: Interventional
• Actual Enrollment: 146 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Infliximab (Remicade®) as an Adjunct to Pegylated- Interferon α-2b and Ribavirin in the Treatment of Hepatitis C Virus Infection
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Infliximab Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab	Drug: Infliximab; Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46; Other Names: Remicade
Placebo Comparator: Placebo Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. A Comparison of the Percentage of Chronic Hepatitis C Subjects (Treatment Naive,Genotype 1) Who Achieve SVR at Week 72, After 48 Weeks of Treatment. [72 Weeks from initiation of treatment]

   A comparison of the Proportion of Chronic Hepatitis C Subjects (Treatment Naive,Genotype 1) Who Achieve SVR at Week 72, After 48 Weeks of TreatmentSVR in both study arms

2. Number of Participants Achieving Sustained Virological Response (SVR) [24 weeks after completion of all study medications]

   HCV RNA negativity at 24 weeks after completion of all study medications

Secondary Outcome Measures

1. A Comparison of the Percentage of Participants With Non-detectable HCV-RNA After 24 Weeks of Therapy. [24 weeks]

   A comparison of the proportion of the subject population with non-detectable HCV-RNA after 24 wks of therapy.

2. Percentage of Participants Experiencing Serious Adverse Events [72 Weeks from initiation of treatment]

   The severity of adverse events was graded according to modified World Health Organization grades as mild, moderate, severe, or life-threatening

3. Percentage of Participants Experiencing Medically Significant Infections [72 weeks from initiation of treatment]

   Medically significant infection was defined as an infection requiring the use of intravenous antibiotics or hospitalization.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female subjects, >18 years of age with proven chronic (greater than 6 months) hepatitis C infection (genotype 1) who have never been treated with pegylated interferon α-2b and /or ribavirin.

Criteria for inclusion in this trial are as follows:

• Male or female, 18 years of age or older

• Positive HCV RNA, Genotype 1, treatment naïve (never received pegylated interferon and / or ribavirin)

• Evidence of chronic HCV infection for at least six months prior to screening

• Findings on liver biopsy within the past 36 months that are consistent with the presence of chronic hepatitis C infection.

• Negative hepatitis B surface antigen

• No evidence of hemochromatosis

• Hemoglobin ≥12 g/dL for females and ≥13 g/dL for males

• WBC ≥3.0 x 109/L and neutrophils ≥1.5 x 109/L

• Platelets ≥80 x109/L

• Direct Bilirubin WNL +/- 50% of central laboratory normal range. Total bilirubin ≤1.6.

• Albumin within normal limits

• Serum creatinine within normal limits.

• Serum thyroid stimulating hormone (TSH) levels within normal limits

• Men and women of childbearing potential must use two forms of adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.

• Subjects with a history of mild depression may be considered for entry into this study.

• No history of latent or active TB.

Exclusion Criteria:

• Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion and men with partners who are pregnant at baseline or intend to become pregnant within 6 months after the last infusion.

• Known allergy against infliximab, ribavirin, or pegylated interferon

• Decompensated liver disease characterized as decreased hepatic synthetic functioning with abnormal albumin and bilirubin levels, prolonged prothrombin time or complications including ascites or recent variceal bleeding

• have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidiomycosis (Valley Fever)

• History of autoimmune hepatitis or a history of poorly controlled autoimmune disease

• Use of other systemic anti-inflammatory medication except NSAIDs and low dose systemic steroids

• Previous treatment with monoclonal antibodies or antibody fragments

• History of receiving human/murine recombinant products or a known allergy to murine products

• Documentation of seropositive for human immunodeficiency virus (HIV)

• History of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results

• History of serious infections (e.g., hepatitis, pneumonia or pyelonephritis) in the previous 3 months

• Opportunistic infection within 6 months prior to screening

• History of lymphoproliferative disease

• Currently have any known malignancy or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence

• Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease

• Treatment with any other therapeutic agent targeted at reducing TNF within 3 months of screening

• Presence of a transplanted solid organ

• Concomitant diagnosis or history of congestive heart failure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center, Center for Liver Disease and Transplantation	Los Angeles	California	United States	90048
2	Advanced Medical Research Center	Port Orange	Florida	United States	32127
3	University of Louisville	Louisville	Kentucky	United States	440292
4	Case Medical Center	Cleveland	Ohio	United States	44106
5	Cleveland Clinic	Cleveland	Ohio	United States	44195
6	The Liver Institute at Methodist Dallas	Dallas	Texas	United States	75203
7	Brooke Army Medical Center	San Antonio	Texas	United States	78234

Sponsors and Collaborators

• Nizar Zein
• Centocor, Inc.

Investigators

• Principal Investigator: Nizar N Zein, MD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nizar Zein, Associate Professor of Medicine; Chief, Section of Hepatobiliary Diseases; Medical Director of Liver Transplantation, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT00512278
• Other Study ID Numbers: PARTNER
• First Posted: Aug 7, 2007
• Last Update Posted: Sep 13, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Nizar Zein, Associate Professor of Medicine; Chief, Section of Hepatobiliary Diseases; Medical Director of Liver Transplantation, The Cleveland Clinic: Hepatitis; HCV; Hepatitis C
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Infliximab

Study Results

Participant Flow

Recruitment Details	Enrollment 2007-2011 Data Lock Nov 22, 2012 Sites The Cleveland Clinic University Hospitals of Cleveland Cedar Sinai Medical Center, Los Angeles, The Liver Institute at Methodist Dallas Brooke Army Medical Center, San Antonio Advanced Medical Research Center, Daytona Beach. University of Louisville, Louisville
Pre-assignment Detail	220 subjects screened and 149 randomized Reasons for exclusion were multiple including malignancy, liver failure, negative HCV RNA, abnormal lab values, poorly controlled diabetes, psych disorders, positive tuberculosis skin test, seizure disorder, inability to get labs or liver biopsy, pregnancy, patient declining, other (cardiomypathy, MS, etc.)

Arm/Group Title	A Infliximab	B Placebo
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients received triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients received triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed similar to infliximab for patients in arm A of the study
Period Title: Overall Study
STARTED	73	73
COMPLETED	45	56
NOT COMPLETED	28	17

Baseline Characteristics

Arm/Group Title	A Infliximab	B Placebo	Total
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients received triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients received triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed similar to infliximab for patients in arm A of the study	Total of all reporting groups
Overall Participants	73	73	146
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	73 100%	73 100%	146 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.7 (9.78)	47.2 (9.38)	46.9 (9.58)
Sex: Female, Male (Count of Participants)
Female	33 45.2%	31 42.5%	64 43.8%
Male	40 54.8%	42 57.5%	82 56.2%
Region of Enrollment (participants) [Number]
United States	73 100%	73 100%	146 100%

Outcome Measures

1. Primary Outcome

Title	A Comparison of the Percentage of Chronic Hepatitis C Subjects (Treatment Naive,Genotype 1) Who Achieve SVR at Week 72, After 48 Weeks of Treatment.
Description	A comparison of the Proportion of Chronic Hepatitis C Subjects (Treatment Naive,Genotype 1) Who Achieve SVR at Week 72, After 48 Weeks of TreatmentSVR in both study arms
Time Frame	72 Weeks from initiation of treatment

Outcome Measure Data

Analysis Population Description

Included all patients who received at least one dose of treatment in both study arms

Arm/Group Title	A Infliximab	B Placebo
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients received triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients received triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed similar to infliximab for patients in arm A of the study
Measure Participants	73	73
Number [percentage of participants]	28.8 39.5%	31.5 43.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A Infliximab, B Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assuming a 25% difference in the rate of SVR between the PEG INF/RBV plus infliximab group (70%) and the PEG INF/RBV (45%) group, a power of 0.85 and an alpha level of 0.05, 75 patients for each group was estimated
Statistical Test of Hypothesis	p-Value	0.718
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	A Comparison of the Percentage of Participants With Non-detectable HCV-RNA After 24 Weeks of Therapy.
Description	A comparison of the proportion of the subject population with non-detectable HCV-RNA after 24 wks of therapy.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A Infliximab	B Placebo
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed simialr to infliximab for patients in arm A of the study
Measure Participants	73	73
Count of Participants [Participants]	40 54.8%	41 56.2%

3. Primary Outcome

Title	Number of Participants Achieving Sustained Virological Response (SVR)
Description	HCV RNA negativity at 24 weeks after completion of all study medications
Time Frame	24 weeks after completion of all study medications

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A Infliximab	B Placebo
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed simialr to infliximab for patients in arm A of the study
Measure Participants	73	73
Count of Participants [Participants]	21 28.8%	23 31.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A Infliximab, B Placebo
	Comments	SVR was the primary outcome to calculate sample size. Assuming a 25% difference in the rate of SVR between the the two groups, a power of 0.85 and an alpha level of 0.05, 75 patients for each group was estimated. This analysis included patients randomized and received at least one dose of study drugs. A 2-sided probability value of < 0.05 was considered statistically significant. Univariate and multivariable logistic regression were used for factors associated with an SVR.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assuming a 25% difference in the rate of SVR between the PEG INF/RBV plus infliximab group (70%) and the PEG INF/RBV (45%) group, a power of 0.85 and an alpha level of 0.05, 75 patients for each group was estimated.
Statistical Test of Hypothesis	p-Value	0.718
	Comments	Univariate and multivariable logistic regression were used for factors associated with an SVR.
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Percentage of Participants Experiencing Serious Adverse Events
Description	The severity of adverse events was graded according to modified World Health Organization grades as mild, moderate, severe, or life-threatening
Time Frame	72 Weeks from initiation of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A Infliximab	B Placebo
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed simialr to infliximab for patients in arm A of the study
Measure Participants	73	73
Count of Participants [Participants]	21 28.8%	13 17.8%

5. Secondary Outcome

Title	Percentage of Participants Experiencing Medically Significant Infections
Description	Medically significant infection was defined as an infection requiring the use of intravenous antibiotics or hospitalization.
Time Frame	72 weeks from initiation of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A Infliximab	B Placebo
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed simialr to infliximab for patients in arm A of the study
Measure Participants	73	73
Count of Participants [Participants]	10 13.7%	3 4.1%

Adverse Events

Time Frame	72 weeks
Arm/Group Title	A Infliximab		B Placebo
Arm/Group Description	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab Infliximab : Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46 All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/infliximab) at approved doses		Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV Placebo : Placebo All patients recieved triple therapy (pegylated interferon (PEG IFN)/ribavirin/placebo) at approved doses. Placebo infusions were timed simialr to infliximab for patients in arm A of the study
All Cause Mortality
	A Infliximab		B Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		1/73 (1.4%)
Serious Adverse Events
	A Infliximab		B Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/73 (28.8%)		13/73 (17.8%)
Blood and lymphatic system disorders
Anemia	4/73 (5.5%)		2/73 (2.7%)
Cardiac disorders
Myocardial Infarction	1/73 (1.4%)		0/73 (0%)
General disorders
Severe Dehydration	3/73 (4.1%)		1/73 (1.4%)
Chest Pain	1/73 (1.4%)		0/73 (0%)
Infections and infestations
Medically Significant Infections	10/73 (13.7%)		3/73 (4.1%)
Nervous system disorders
Coordination Abnormal	0/73 (0%)		1/73 (1.4%)
Depressed level of consciousness	0/73 (0%)		1/73 (1.4%)
Headache	0/73 (0%)		1/73 (1.4%)
Psychiatric disorders
Depression	0/73 (0%)		1/73 (1.4%)
Suicidal Ideation	1/73 (1.4%)		3/73 (4.1%)
Vascular disorders
Deep Vein Thrombosis	1/73 (1.4%)		0/73 (0%)
Other (Not Including Serious) Adverse Events
	A Infliximab		B Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/73 (100%)		73/73 (100%)
Blood and lymphatic system disorders
Anemia	19/73 (26%)		19/73 (26%)
Neutropenia	10/73 (13.7%)		6/73 (8.2%)
Gastrointestinal disorders
Nausea	36/73 (49.3%)		41/73 (56.2%)
Diarrhea	11/73 (15.1%)		23/73 (31.5%)
General disorders
Fatigue	55/73 (75.3%)		54/73 (74%)
Influenza-Like Illness	23/73 (31.5%)		17/73 (23.3%)
Irritability	20/73 (27.4%)		21/73 (28.8%)
Pyrexia	21/73 (28.8%)		26/73 (35.6%)
Chills	13/73 (17.8%)		28/73 (38.4%)
Infections and infestations
Any Infection	48/73 (65.8%)		42/73 (57.5%)
Musculoskeletal and connective tissue disorders
Myalgia	24/73 (32.9%)		22/73 (30.1%)
Arthralgia	39/73 (53.4%)		25/73 (34.2%)
Nervous system disorders
Headache	42/73 (57.5%)		39/73 (53.4%)
Dizziness	14/73 (19.2%)		16/73 (21.9%)
Psychiatric disorders
Insomnia	31/73 (42.5%)		27/73 (37%)
Depression	21/73 (28.8%)		25/73 (34.2%)
Respiratory, thoracic and mediastinal disorders
Cough	16/73 (21.9%)		27/73 (37%)
Skin and subcutaneous tissue disorders
Pruritus	22/73 (30.1%)		26/73 (35.6%)
Rash	29/73 (39.7%)		23/73 (31.5%)
Alopecia	18/73 (24.7%)		17/73 (23.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.