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

• ClinicalTrials.gov Identifier: NCT00736242
• Recruitment Status: Completed
• First Posted: August 15, 2008
• Results First Posted: April 8, 2013
• Last Update Posted: February 19, 2015
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

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.

Condition or disease	Intervention/treatment
Chronic Hepatitis C; Hepatitis C; HIV Infections	Biological: PEG-IFN alfa-2b; Drug: RBV

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 Design

• Study Type: Observational
• Actual Enrollment: 232 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Treatment of Chronic Hepatitis C in HIV-infected Patients With PegIntron Pen and Rebetol According to German Law (§ 67 Abs 6 AMG)
• Study Start Date: December 2005
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Groups and Cohorts

Group/Cohort	Intervention/treatment
PEG-IFN alfa-2b + 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.	Biological: PEG-IFN alfa-2b; Peginterferon alfa-2b administered subcutaneously at a dose 1.5 ug/kg/week, according to the European Medicines Agency (EMEA)-approved labeling; Other Names: SCH 054031; PegIntron; Drug: RBV; Ribavirin administered at a dose of 800-1200 mg/day (on a weight-basis) according to the EMEA-approved labeling; Other Names: Rebetol; SCH 018908

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Sustained Virologic Response (SVR) [ Time Frame: 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 :

1. Number of Participants With Rapid Virologic Response (RVR) [ Time Frame: At Treatment Week 4 ]
   RVR was defined as undetectable serum HCV-RNA at week 4.
2. Number of Participants With Early Virologic Response (EVR) [ Time Frame: 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.

3. Participant Study Status at End of Follow-up (EOF) [ Time Frame: 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.

4. Number of Participants With Hepatitis C Virus (HCV)-RNA Negativity During PEG-IFN Alfa-2b/RBV Treatment [ Time Frame: 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.

5. Number of Participants With Human Immunodeficiency Virus (HIV)-RNA Negativity During PEG-IFN Alfa-2b/RBV Treatment [ Time Frame: 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

6. Median Cluster of Differentiation 4 (CD4) Cell Count During PEG-IFN Alfa-2b/RBV Treatment [ Time Frame: 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.
7. Number of Participants With A Serious Adverse Event (SAE) During PEG-IFN Alfa-2b/RBV Treatment [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Subjects coinfected with HIV and HCV seen in common medical practice by general practitioners and clinical doctors at 30 sites all over Germany.

Criteria

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

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00736242 History of Changes
• Other Study ID Numbers: P04584
• First Posted: August 15, 2008
• Results First Posted: April 8, 2013
• Last Update Posted: February 19, 2015
• Last Verified: February 2015

Keywords provided by Merck Sharp & Dohme Corp.:

HIV

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Hepatitis, Viral, Human; Interferon-alpha; Interferon alpha-2; Ribavirin; Liver Diseases; Digestive System Diseases; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Peginterferon alfa-2b; Antiviral Agents; Anti-Infective Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action