A Randomized, Open-label, Multi-center, Phase 3, 2-arm Study Evaluating the Efficacy and Safety of Peg interferon Alfa-2b Low-dose Maintenance Monotherapy Versus Standard Supportive Care in Patients With Cirrhotic Hepatitis C Co-infected With Human Immunodeficiency Virus – The ENDURE Study. - ENDURE
- Conditions
- Cirrhotic Hepatitis C Co-infected With Human Immunodeficiency VirusMedDRA version: 9.0 Level: LLT Classification code 10019641
- Registration Number
- EUCTR2005-003876-39-BE
- Lead Sponsor
- Integrated Therapeutics Group, Incorporated-a subsidiary of Schering Plough
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 448
To be eligible for enrollment, subjects must meet the following inclusion criteria:
1) Display the willingness and ability to participate in the study by demonstrating full comprehension of and agreement to comply with all study procedures by signing the written informed consent.
2) =18 years but < 70 years, of either sex or any race.
3) Detectable plasma HCV RNA with all genotypes of HCV permitted. Historical PCR and genotype are acceptable for study entry and will be confirmed at screening through the central lab.
4) Previous non-responders or intolerant to any pegylated alpha interferon plus ribavirin (cannot be on therapy for 2 weeks prior to randomization) or subjects unwilling to complete a full course of any combination treatment (pegylated alpha interferon plus ribavirin) are eligible for this study.
5) Cirrhosis of the liver, confirmed by histopathologic findings.
6) Compensated liver disease measured by the Child-Pugh clinical classification with the hepatic encephalopathy measure equal to one and the total score less than or equal to 8.
7) No evidence of HCC on abdominal ultrasound, CT scan, or MRI scan, and a serum AFP <100 ng/mL within 90 days of randomization/study .
8) Endoscopy to determine if evidence of bleeding (prior or present) due to esophageal varices, gastric varices, or portal gastropathy within six months of randomization/study enrollment. (If evidence of prior variceal bleeding, the patient is not eligible for the study).
9) Serologic evidence of HIV infection by HIV antibody or detection of HIV RNA. (Historical HIV RNA is acceptable for study entry and will be confirmed at screening through a central lab).
10) CD4 cell count =100 /µL, regardless of HIV RNA load.
11) Platelet number of at least 50000 mm3.
12) Neutrophil count of at least 750 mm3.
13) Hemoglobin of >9.0 g/dL.
14) Any serum ALT/AST liver enzyme level.
15) Serum thyroid stimulating hormone levels within normal limits, regardless of treatment with L thyroxin.
16) HbA1c<8.5%, to demonstrate controlled diabetes, if applicable.
17) Written clearance from an ophthalmologist must be presented for subjects with a history of hypertension or diabetes prior to treatment start.
18) Creatinine clearance >50 mL/min, as assessed by the indirect calculation method (Appendix 5).
19) Demonstrate stable status of HIV infection, in the opinion of the principal investigator, (e.g., subjects who are expected to progress in the first 3 months of the study would not be appropriate for enrollment).
20) On stable antiretroviral therapy (HAART) for at least 8 weeks prior to baseline.
OR
21) Willing to delay initiation of HAART therapy for at least 6 weeks (for subjects who have not been on HAART for at least 8 weeks prior to randomization).
22) Counseled in the appropriate use of birth control while in this study, as confirmed by the principal investigator or a sub-investigator.
23) While abstinence from sexual activity is the only certain method to prevent pregnancy, female subjects of childbearing potential (includes women who are less than two years post-menopausal and wom
Any subject will be excluded from entry into the study if they have ANY of the following criteria:
1) Female who is pregnant, intends to become pregnant during the study or within two months after study completion, or is nursing. Male subjects whose partner wants to become pregnant.
2) Using silymarin.
3) Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or HBeAg.
4) Any cause of liver disease other than chronic hepatitis C, including—but not limited to:
a) Hemochromatosis
b) Alpha-1 antitrypsin deficiency
c) Wilson's disease
d) Autoimmune hepatitis
e) Alcoholic liver disease
f) Non-alcoholic steatohepatitis (NASH)
g) Drug-related liver disease
5) Suspected or having hypersensitivity to interferon.
6) History of liver decompensation status or other evidence of bleeding from esophageal varices, signs of current bleeding, significant ascites, hepatic encephalopathy, jaundice or other conditions consistent with decompensated liver disease.
7) Present with a lesion suspicious for hepatic malignancy (HCC or metastasis/metastases) on the screening imaging.
8) Any active malignant disease, suspicion, or history of malignant disease within 5 years prior to study enrollment (except for adequately treated basal cell carcinoma).
9) Known coagulation (e.g., hemophilia) or hemoglobin (e.g., thalassemia) diseases that in the opinion of the investigator presents a risk to the patient to participate in the study
10) Organ transplant, except corneal or hair transplant.
11) Any known preexisting medical condition that, in the investigator’s opinion, could interfere with the subject's participation in and completion of the study, such as:
a) Preexisting psychiatric condition, especially moderate to severe depression, or a history of severe psychiatric disorder, such as psychosis, suicidal ideation, or suicide attempts. Severe depression includes the following:
i) Hospitalization for depression
ii) Electroconvulsive therapy for depression, or
iii) Depression causing a prolonged absence from work or significantly altering daily functions.
Subjects with mild depression may be considered for entry into the study provided that a pre-treatment assessment demonstrates that the subject’s emotional status is clinically stable (either on or off drugs), in which case a management plan must be formulated for the subject; this management plan will become a part of the subject 's medical record.
b) Craniocerebral trauma which is not a concussion, or active seizure disorders requiring medication
c) Clinically significant ECG abnormalities and/or cardiovascular dysfunction within six previous months (e.g., angina, congestive heart failure, recent myocardial infarction, or significant arrhythmia)
d) Chronic lung disease (e.g., chronic obstructive lung disease)
e) Poorly controlled diabetes mellitus
f) Immune-mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, sc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method