Trial Outcomes & Findings for PHOENIX Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) and COPEGUS (Ribavirin) Administered After Liver Transplantation for Hepatitis C. (NCT NCT00087633)

Last Updated: 2018-03-29

Results Overview

Histologically-confirmed recurrence of HCV defined as Batts-Ludwig inflammation grade ≥3 and/or fibrosis stage ≥2. Inflammation(Grade): 0 No Activity,1 Minimal,2 Mild,3 Moderate,4 Severe. Fibrosis (Stage): 0 No fibrosis, Normal; 1 Portal fibrosis; 2 Periportal fibrosis or rare portal septa; 3 Septal fibrosis, Fibrous septa with architectural distortion, no obvious cirrhosis; 4 Cirrhosis.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

115 participants

Primary outcome timeframe

120 weeks postrandomization

Results posted on

2018-03-29

Participant Flow

Patients were recruited from 24 study centers in the US over a period of 4 years (12-Oct-04 - 17-Oct-08)

Eligible for the study were male or female patients ≥18 years of age with HCV infection who underwent orthotopic liver transplantation (OLT) because of liver cirrhosis attributed to HCV infection

Participant milestones

Participant milestones
Measure	Prophylaxis Arm Pegylated interferon alfa-2a subcutaneously (SC) 135 μg/week for 4 weeks, then increased to 180 μg/week for the next 44 weeks, plus Ribavirin orally 400 mg/day (initial) to 1000 mg/day for patients \<75 kg or 1200 mg/day for patients ≥75 kg PO (escalated) (maximum) administered orally	Observation Arm No antiviral therapy for HCV unless recurrence of HCV was histologically demonstrated. Once histological recurrence was demonstrated, patients received the same antiviral regimen as patients in the prophylaxis arm (ie, 48 weeks of combined PEG-IFN alfa-2a and ribavirin)
Overall Study STARTED	55	60
Overall Study COMPLETED	31	43
Overall Study NOT COMPLETED	24	17

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PHOENIX Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) and COPEGUS (Ribavirin) Administered After Liver Transplantation for Hepatitis C.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prophylaxis Arm n=55 Participants Pegylated interferon alfa-2a subcutaneously (SC) 135 μg/week for 4 weeks, then increased to 180 μg/week for the next 44 weeks, plus Ribavirin orally 400 mg/day (initial) to 1000 mg/day for patients \<75 kg or 1200 mg/day for patients ≥75 kg PO (escalated) (maximum) administered orally	Observation Arm n=60 Participants No antiviral therapy for HCV unless recurrence of HCV was histologically demonstrated. Once histological recurrence was demonstrated, patients received the same antiviral regimen as patients in the prophylaxis arm (ie, 48 weeks of combined PEG-IFN alfa-2a and ribavirin)	Total n=115 Participants Total of all reporting groups
Age, Continuous	51.3 years STANDARD_DEVIATION 6.09 • n=5 Participants	53.6 years STANDARD_DEVIATION 5.37 • n=7 Participants	52.5 years STANDARD_DEVIATION 5.82 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	48 Participants n=7 Participants	93 Participants n=5 Participants
Region of Enrollment United States	55 participants n=5 Participants	60 participants n=7 Participants	115 participants n=5 Participants

PRIMARY outcome

Timeframe: 120 weeks postrandomization

Population: Intent-to-treat population

Outcome measures

Outcome measures
Measure	Prophylaxis Arm n=55 Participants Pegylated interferon alfa-2a subcutaneously (SC) 135 μg/week for 4 weeks, then increased to 180 μg/week for the next 44 weeks, plus Ribavirin orally 400 mg/day (initial) to 1000 mg/day for patients \<75 kg or 1200 mg/day for patients ≥75 kg PO (escalated) (maximum) administered orally	Observation Arm n=60 Participants No antiviral therapy for HCV unless recurrence of HCV was histologically demonstrated. Once histological recurrence was demonstrated, patients received the same antiviral regimen as patients in the prophylaxis arm (ie, 48 weeks of combined PEG-IFN alfa-2a and ribavirin)
Percentage of Patients With Histologically-confirmed Recurrence of Hepatitis C Virus (HCV)	61.8 percentage of participants	65.0 percentage of participants

SECONDARY outcome

Timeframe: After 4, 12, 24 and 48 weeks of therapy, and 24 weeks of follow-up

Population: ITT population

Rapid virologic responder (RVR): undetectable HCV-RNA at Week 4; complete early virologic responder (cEVR): undetectable HCV-RNA at Week 12; partial early virologic responder (pEVR): ≥2 log10 drop from baseline in HCV-RNA but positive at Week 12; early virologic responder (EVR): undetectable HCV-RNA or ≥2 log10 drop from baseline in HCV-RNA at Week 12; 24 weeks negative: undetectable HCV-RNA at Week 24; 48 weeks negative: undetectable HCV-RNA at Week 48; sustained virologic response (SVR): undetectable HCV-RNA at 24 weeks after the end of treatment.

Outcome measures

Outcome measures
Measure	Prophylaxis Arm n=54 Participants Pegylated interferon alfa-2a subcutaneously (SC) 135 μg/week for 4 weeks, then increased to 180 μg/week for the next 44 weeks, plus Ribavirin orally 400 mg/day (initial) to 1000 mg/day for patients \<75 kg or 1200 mg/day for patients ≥75 kg PO (escalated) (maximum) administered orally	Observation Arm n=14 Participants No antiviral therapy for HCV unless recurrence of HCV was histologically demonstrated. Once histological recurrence was demonstrated, patients received the same antiviral regimen as patients in the prophylaxis arm (ie, 48 weeks of combined PEG-IFN alfa-2a and ribavirin)
Summary of Virologic Response Rapid virologic responder (RVR)	4 participants	0 participants
Summary of Virologic Response Complete early virologic responder (cEVR)	14 participants	4 participants
Summary of Virologic Response Partial early virologic responder (pEVR)	13 participants	3 participants
Summary of Virologic Response 48 weeks negative	18 participants	3 participants
Summary of Virologic Response Sustained virologic responder (SVR)	12 participants	3 participants
Summary of Virologic Response Early virologic responder (EVR)	27 participants	7 participants
Summary of Virologic Response 24 weeks negative	20 participants	6 participants

Adverse Events

Prophylaxis Arm

Serious events: 25 serious events

Other events: 54 other events

Deaths: 0 deaths

Observation Arm

Serious events: 21 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Prophylaxis Arm n=54 participants at risk Pegylated interferon alfa-2a subcutaneously (SC) 135 μg/week for 4 weeks, then increased to 180 μg/week for the next 44 weeks, plus Ribavirin orally 400 mg/day (initial) to 1000 mg/day for patients \<75 kg or 1200 mg/day for patients ≥75 kg PO (escalated) (maximum) administered orally	Observation Arm n=60 participants at risk No antiviral therapy for HCV unless recurrence of HCV was histologically demonstrated. Once histological recurrence was demonstrated, patients received the same antiviral regimen as patients in the prophylaxis arm (ie, 48 weeks of combined PEG-IFN alfa-2a and ribavirin)
Infections and infestations Infections and infestations	11.1% 6/54 • Number of events 7 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	10.0% 6/60 • Number of events 8 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Gastrointestinal disorders Gastrointestinal disorders	14.8% 8/54 • Number of events 8 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	1.7% 1/60 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Hepatobiliary disorders Hepatobiliary disorders	11.1% 6/54 • Number of events 6 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	5.0% 3/60 • Number of events 3 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Blood and lymphatic system disorders Blood and lymphatic system disordersimag	11.1% 6/54 • Number of events 6 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	3.3% 2/60 • Number of events 2 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Cardiac disorders Cardiac disorders	0.00% 0/54 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	3.3% 2/60 • Number of events 2 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Investigations Investigations	3.7% 2/54 • Number of events 2 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	0.00% 0/60 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Surgical and medical procedures Surgical and medical proceduresi	0.00% 0/54 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	3.3% 2/60 • Number of events 2 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Endocrine disorders Endocrine disorders	1.9% 1/54 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	0.00% 0/60 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Immune system disorders Immune system disorders	1.9% 1/54 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	0.00% 0/60 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Reproductive system and breast disorders Reproductive system and breast disorders	1.9% 1/54 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	0.00% 0/60 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	0.00% 0/54 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	1.7% 1/60 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
General disorders General disorders and administration site conditions	9.3% 5/54 • Number of events 5 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	1.7% 1/60 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Injury, poisoning and procedural complications Injury, poisoning and procedural complicationsE	1.9% 1/54 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	6.7% 4/60 • Number of events 4 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Nervous system disorders Nervous system disorders	7.4% 4/54 • Number of events 4 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	0.00% 0/60 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Metabolism and nutrition disorders Metabolism and nutrition disorders	5.6% 3/54 • Number of events 4 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	1.7% 1/60 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Renal and urinary disorders Renal and urinary disorders	5.6% 3/54 • Number of events 3 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	1.7% 1/60 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	1.9% 1/54 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	3.3% 2/60 • Number of events 2 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.
Vascular disorders Vascular disorders	1.9% 1/54 • Number of events 1 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.	3.3% 2/60 • Number of events 2 • Adverse Events were collected for the period of the study (4 years, 12-Oct-2004 - 17-Oct-2008) Safety Population: 54 patients in the prophylaxis arm, and 60 patients in the observation arm. One patient randomized to the prophylaxis arm was excluded from the safety population because they withdrew consent before receiving any study medication and did not have any postbaseline assessments.