Efficacy and Safety of PegIntron Plus Ribavirin for Treatment of Chronic Hepatitis C in HIV-Infected Subjects (Study P04469)(TERMINATED)

HIV Infections Clinical Trial

Official title:

Efficacy and Safety of PegIntron Plus Ribavirin for Treatment of Chronic Hepatitis C Infection in HIV-Infected Persons Not Previously Treated With Interferon

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00687544
• Other study ID #: P04469
• Status: Terminated
• Phase: Phase 4
• First received: May 27, 2008
• Last updated: September 11, 2015
• Start date: December 2005
• Est. completion date: September 2008

Study information

• Verified date: September 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Indonesia: National Agency of Drug and Food Control
• Study type: Interventional

Clinical Trial Summary

In this study, adult Indonesian subjects with human immunodeficiency virus (HIV) coinfected with chronic hepatitis C (CHC) will be given peginterferon alfa-2b (PEG-IFN) plus ribavirin (RBV) combination therapy. The efficacy rate (sustained virologic response, end of treatment virologic response, and sustained biochemical response), the subject morbidity rate as caused by other opportunistic infection (eg, bacterial pneumonia, tuberculosis, and other bacterial infection), and the safety and tolerability of this combination therapy will be examined.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Previously untreated chronic hepatitis C with HCV-RNA positive in plasma.

• Must have finished the detoxification phase of a drug rehabilitation program and abstained for at least 6 weeks from using abused substance (alcohol, I.V. drugs and inhaled drugs) before starting therapy.

• Liver transaminases (alanine aminotransferase [ALT]) 1.5-fold above the upper limit of normal.

• Controlled HIV infection with a viral load <10,000 copies/mL and a CD4 cell (T-cell) count >200 x 10^6 cells/L, in response to a stable antiretroviral treatment (ART) or without ART if it is not required.

• Compensated liver disease with protocol-specified minimum hematologic, biochemical, and serologic criteria at the Entry visit.

• Alpha-fetoprotein value within normal limits obtained within one year prior to entry. Results above the upper limit of normal but <=50 ng/mL require both of the following: Alpha-fetoprotein value <=50 ng/mL obtained within 3 months prior to entry in the study and Ultrasound obtained within 3 months prior to entry in the study or that is negative for evidence of hepatocellular carcinoma.

• Liver biopsy (optional) within 12 months prior to study entry with a pathology report confirming that the histologic diagnosis is consistent with chronic hepatitis.

• Women of childbearing potential must be using an acceptable method of birth control or be surgically sterilized.

• Reconfirmation that sexually active males must be practicing acceptable methods of contraception during the treatment period and for 6 months after discontinuation of therapy.

• Subjects must be free of any clinically significant diseases other than hepatitis or HIV infection that would interfere with study evaluations.

Exclusion Criteria:

• Suspected hypersensitivity to interferon, PEG-interferon, or ribavirin.

• HIV therapy using didanosine (ddI) and stavudine (d4T) in their HIV medications, due to the potentiality of the resulting lactic acidosis.

• Participation in any other clinical trial within 30 days of entry to this protocol.

• Treatment with any investigational drug within 30 days of entry to this protocol.

• Subjects with organ transplants other than cornea and hair transplant.

• Any cause for the liver disease based on subject history and biopsy (where applicable) other than chronic hepatitis C, including but not limited to coinfection with hepatitis B virus (HBV); hemochromatosis (iron deposition >2+ in liver parenchyma); alpha-1 antitrypsin deficiency; Wilson's disease; autoimmune hepatitis; alcoholic liver disease; obesity-induced liver disease.

• Hemophilia or any other condition that would prevent the subject from having a liver biopsy, including anticoagulant therapy.

• Hemoglobinopathies (eg, Thalassemia)

• Evidence of advanced liver disease such as history or presence of ascites, bleeding varices, and encephalopathy.

• Any known preexisting medical condition that could interfere with the subject's participation in and completion of the protocol such as preexisting psychiatric condition, especially severe depression, or a history of severe psychiatric disorder.

• Significant cardiovascular dysfunction within the past 6 months (eg, angina, congestive heart failure, recent myocardial infarction, severe hypertension, or significant arrhythmia). Subjects with electrocardiogram (ECG) showing clinically significant abnormalities.

• Poorly controlled diabetes mellitus.

• Chronic pulmonary disease (eg, chronic obstructive pulmonary disease).

• Immunologically mediated disease.

• Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids.

• Clinical gout.

• Clinically significant retinal abnormalities.

• Alcohol consumption of >20 gr/day.

• Women who are pregnant or nursing.

• Subjects who have not observed the designated washout periods for any of the prohibited medications.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepacivirus
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• HIV Infections

Intervention

Biological:
• Peginterferon alfa-2b (SCH 054031)
Subjects will be given peginterferon alfa-2b (PEG-IFN) subcutaneously, at a dose of 1.5 ug/kg weekly. Treatment duration will be 48 weeks for subjects with Hepatitis C Virus (HCV) genotype 1 and 24 weeks for subjects with HCV genotype 2 or 3 and baseline Hepatitis C Virus-ribonucleic acid (HCV-RNA) below 800,000 IU/mL.

Drug:
• Ribavirin (SCH 018908)
Subjects will be given ribavirin 800 mg/day orally(PO) when body weight is <65 kg, 1000 mg/day when body weight is between 65 kg and 85 kg, and 1200 mg/day when body weight is >85 kg. Treatment duration will be 48 weeks for subjects with HCV genotype 1 and 24 weeks for subjects with HCV genotype 2 or 3 and baseline HCV-RNA below 800,000 IU/mL.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Achieved Sustained Virologic Response (SVR)	Treatment duration for genotype 1 participants was 48 weeks. Treatment duration for genotypes 2 & 3 participants who had baseline hepatitis c virus ribonucleic acid [HCV-RNA] <800,000 IU/mL was 24 weeks.; SVR was defined as plasma HCV RNA level below lower level of quanitation at the end of 24 weeks follow-up (week 48 or 72).; The study was terminated due to low enrollment. This analysis was not performed.	Week 48 or Week 72 (depending on duration of treatment)	No
Primary	Number of Participants Who Achieved Virologic Response (VR)	Treatment duration for genotype 1 participants was 48 weeks. Treatment duration for genotypes 2 & 3 participants who had baseline hepatitis c virus ribonucleic acid [HCV-RNA] <800,000 IU/mL was 24 weeks.; The study was terminated due to low enrollment. This analysis was not performed.	24 Weeks or 48 Weeks (depending on duration of treatment, which was either 24 or 48 weeks)	No
Primary	Number of Participants Who Achieved Sustained Biochemical Response (SBR)	Treatment duration for genotype 1 participants was 48 weeks. Treatment duration for genotypes 2 & 3 participants who had baseline hepatitis c virus ribonucleic acid [HCV-RNA] <800,000 IU/mL was 24 weeks.; SBR was defined as the presence of normal alanine aminotransferase (ALT) values at the end of 24 weeks follow-up (week 48 or 72).; The study was terminated due to low enrollment. This analysis was not performed.	Week 48 or Week 72 (depending on duration of treatment, which was either 24 or 48 weeks)	No
Secondary	Number of Participants Experiencing Opportunistic Infection	The study was terminated due to low enrollment. This analysis was not performed.	Throughout the study (up to 72 weeks)	No
Secondary	Number of Participants Who Died		Throughout the study (up to 72 weeks)	No
Secondary	Number of Participants Experiencing Adverse Events	An adverse event was defined as any untoward medical occurrence in a subject administered a pharmaceutical product, biologic (at any dose), or medical device, which did not necessarily have a causal relationship with the treatment.	Throughout the study (up to 72 weeks)	Yes