Post-marketing Surveillance of HIV-infected Patients With Chronic Hepatitis C Treated With PegIntron Pen and Rebetol (Study P04584)

Completed

• Conditions: Chronic Hepatitis C; Hepatitis C; HIV Infections
• Interventions: Biological: PEG-IFN alfa-2b; Drug: RBV

• Registration Number: NCT00736242
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The objective of the study was to assess the safety and efficacy of peginterferon alfa-2b (PEG-IFN alfa-2b) and ribavirin (RBV) administered to participants coinfected with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). Participants were treated by general practitioners in clinical practice as part of the post-marketing surveillance study. The study assessed the rates of eradication of the HCV and the rates of serious adverse events reported with PEG-IFN alfa-2b (1.5 ug/kg/week) and RBV (800-1200 mg/day) in common medical practice in Germany.

Detailed Description

In this observational, non-interventional study, the time of enrollment and start of treatment was the sole decision of the physician. No investigational medicinal product was provided by the sponsor.

Study Timeline

• Study Start: 2005-12
• Study First Submitted: 2008-07-30
• Study First Submitted QC: 2008-08-14
• Study First Posted: 2008-08-15
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Results First Submitted: 2012-12-21
• Results First Submitted QC: 2013-02-27
• Results First Posted: 2013-04-08
• Status Verified: 2015-02
• Last Update Submitted: 2015-02-02
• Last Update Posted: 2015-02-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 232

Inclusion Criteria

• ≥ 18 years of age eligible for treatment according to the Summary of Product Characteristics (SmPC)
• Presence of chronic Hepatitis C (with elevated liver enzymes and without decompensation)
• Presence of HCV-RNA and known genotype of the infecting hepatitis C virus
• HIV infection confirmed by positive Enzyme Linked Immunosorbent Assay (ELISA) and Western blot and Cluster of differentiation (CD) 4 cell count >200/mL
• Treatment-naïve
• Platelets ≥ 75,000/mm^3
• Neutrophil counts ≥ 1,500/mm^3
• Thyroid Stimulating Hormone (TSH) must be within normal limits
• Hemoglobin ≥ 10 g/dL (females); ≥ 11 g/dL (males)
• Women of childbearing potential must have a routine pregnancy test performed monthly during treatment and for 7 months thereafter. Sexually active female participants of childbearing potential must be practicing adequate contraception (intrauterine device, oral contraceptives, implanted contraceptives, surgical sterilization, barrier method, or monogamous relationship with a male partner who has had a vasectomy or is using a condom (+ spermicide) during the treatment period and for 7 months after stopping treatment.
• Sexually active male participants must be practicing acceptable methods of contraception (vasectomy, use of condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 7 months after stopping treatment.

Exclusion Criteria

• Contraindications according to the European approval and to the SmPC
• Pretreatment of chronic hepatitis C
• Liver decompensation
• Hypersensitivity to the active substance or to any interferons or to any of the excipients
• Pregnant woman
• Women who are breast feeding
• Existence of or history of psychiatric condition, particular depression, suicidal ideation or suicide attempt
• A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months
• Severe debilitating medical conditions, including participants with chronic renal failure or creatinine clearance < 50 ml/min.
• Autoimmune hepatitis or history of autoimmune disease
• Severe hepatic dysfunction or decompensated cirrhosis of the liver
• Pre-existing thyroid disease unless it can be controlled with conventional therapy
• Epilepsy and/or compromised central nervous system function

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PEG-IFN alfa-2b + RBV	PEG-IFN alfa-2b	Participants received a combination of PEG-IFN alfa-2b plus RBV according to routine clinical practice and locally-approved product recommendations for a minimum of 12 weeks. No investigational medicinal product was provided by the sponsor.
PEG-IFN alfa-2b + RBV	RBV	Participants received a combination of PEG-IFN alfa-2b plus RBV according to routine clinical practice and locally-approved product recommendations for a minimum of 12 weeks. No investigational medicinal product was provided by the sponsor.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Sustained Virologic Response (SVR)	From End of Treatment to 24 weeks post-treatment (up to 72 weeks)	SVR was defined as undetectable serum Hepatitis C Virus ribonucleic acid (HCV-RNA) at End of Treatment (EOT) and at the End of Follow-up (EOF).

Secondary Outcome Measures

Name	Time	Method
Participant Study Status at End of Follow-up (EOF)	From EOT to EOF (up to 72 weeks)	Participant study status was assessed at the End of Follow-up (defined as 24 weeks after the end of treatment) based on serum levels of HCV-RNA.; SVR was defined as defined as undetectable serum HCV-RNA at EOT and EOF, Relapse was defined as undetectable HCV-RNA at EOT with detectable HCV-RNA at EOF, and Non-response was defined as a detectable serum HCV-RNA at EOT.
Number of Participants With Hepatitis C Virus (HCV)-RNA Negativity During PEG-IFN Alfa-2b/RBV Treatment	From the Baseline Visit up to EOF (up to 72 weeks)	HCV-RNA negativity/positivity was documented at baseline in the medical history (anamnesis), and assessed within the laboratory (lab) at baseline and during treatment by Polymerase Chain Reaction (PCR).; HCV-RNA (+) = HCV-RNA positive, HCV-RNA (-) = HCV-RNA negative, HCV-RNA Missing = HCV-RNA data not documented, not applicable, not known, not examined, or missing.
Number of Participants With Human Immunodeficiency Virus (HIV)-RNA Negativity During PEG-IFN Alfa-2b/RBV Treatment	From the Baseline Visit up to EOF (up to 72 weeks)	HIV-RNA negativity/positivity was documented at baseline in the medical history (anamnesis), and assessed within the laboratory (lab) at baseline and during treatment.; HIV-RNA (+) = HIV-RNA positive, HIV-RNA (-) = HIV-RNA negative, HIV-RNA Missing = HIV-RNA data not documented, not applicable, not known, not examined, or missing
Number of Participants With Rapid Virologic Response (RVR)	At Treatment Week 4	RVR was defined as undetectable serum HCV-RNA at week 4.
Median Cluster of Differentiation 4 (CD4) Cell Count During PEG-IFN Alfa-2b/RBV Treatment	From the Baseline Visit up to EOF (up to 72 weeks)	The CD4 helper T cell count was used to assess participant HIV status and was determined in the laboratory at baseline and during the study course.
Number of Participants With Early Virologic Response (EVR)	From Treatment Week 1 to Treatment Week 12	EVR was defined as undetectable serum HCV-RNA at week 12 and/or a; ≥2 log decline in HCV-RNA levels at week 12 from baseline.
Number of Participants With A Serious Adverse Event (SAE) During PEG-IFN Alfa-2b/RBV Treatment	From First Participant Visit (12/30/2005) up to 30 days after Last Participant Visit (12/31/2011).	An SAE was any adverse drug/biologic/device experience occurring at any dose that resulted in death, was life-threatening (i.e. placed the participant, in the view of the initial reporter, at immediate risk of death from the AE as it occurred), was a persistent or significant disability/incapacity, required in-patient hospitalization, or prolonged hospitalization, or led to a; congenital anomaly or birth defect.