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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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30 April 2019 |
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Main ID: |
EUCTR2005-003876-39-BE |
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Date of registration:
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30/08/2006 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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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
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Scientific title:
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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 |
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Date of first enrolment:
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19/09/2006 |
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Target sample size:
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448 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003876-39 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product:
Placebo:
Other: yes
Other specify the comparator: Standard Supportive Care - defined by local country guidelines
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Belgium
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Key inclusion & exclusion criteria
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Inclusion criteria:
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
Exclusion criteria:
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
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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Cirrhotic Hepatitis C Co-infected With Human Immunodeficiency Virus
MedDRA version: 9.0
Level: LLT
Classification code 10019641
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Intervention(s)
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Trade Name: PegIntron
Product Name: PEGIntron
Product Code: SCH 54031
Pharmaceutical Form: Injection*
INN or Proposed INN: peginterferon alpha-2b/ standard supportive care
CAS Number: 215647-85-1
Current Sponsor code: SCH 54031
Other descriptive name: PEGIntron
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 50 / 50-150 vials / 100 p
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Primary Outcome(s)
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Secondary Objective: To compare the two treatment groups at the EOS:
a) & b) The times and incidence to each of the following EOS: Overall mortality, Liver-related mortality, Liver decompensation, Liver transplants, Hepatocellular carcinoma (HCC)
1. To investigate the safety profile of PEG-Intron in comparison with standard supportive care.
2. To assess the effect of PEG-Intron low dose maintenance treatment on HIV infection progression as determined by: a. changes in CD4 cell count levels, b. changes in HIV RNA titers, c. HIV related infections, d. ART regimen changes.
3. Changes in serum ALT and HCV RNA.
4. Changes in Fibro Scan and APRI during the study period.
5. Changes in hepatic venous pressure gradient (HVPG) levels in a subgroup of subjects from the two treatment groups with available data.
6. Changes in proliferative histological indices and fibrotic scores in a subgroup of paired liver biopsies at the beginning and EOS. Liver biopsies will be obtained from the two treatment groups.
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Primary end point(s): The primary endpoint is to measure the time to the first occurrence of any one of the clinical end points (death, liver decompensation, liver transplant and HCC) in the two treatment groups.
Secondary endpoints include:
1. To measure time to death and incidence of deaths in the two treatment groups.
2. To measure time to liver related deaths and liver related deaths incidence at the end of the study in the two treatment groups.
3. To measure time to liver decompensation and liver decompensation incidence in the two treatment groups.
4. To measure time to liver transplant and transplant incidence in the two treatment groups.
5. To measure time to HCC and HCC incidences in the two treatment groups.
6. To measure incidence of combined clinical events in the two treatment groups.
7. To measure and compare the incidence of the treatment dose discontinuation rate, study discontinuation rate, and total SAE's in subjects in the two treatment groups. Thus, to determine whether PEG-Intron has any in vivo interaction with HAART.
8. To measure the effect of PEG-Intron on low dose maintenance treatment on HIV disease progression:
a. Incidence of subjects with an increase in HIV RNA >0.5 log while on stable HAART therapy.
b. Incidence of subjects with a > 50 CD4 cells/cc drop, or >50% whichever is bigger.
c. Incidence of subjects and time to progression to AIDS defining events- defined in Appendix 7.
d. Incidence of subjects’ HAART regimen modification and/or discontinuation.
9. To measure changes in biochemical markers (serum ALT and APRI) and HCV RNA during the study period.
10. To measure changes in Fibro Scan during the study period.
11. To measure the changes in hepatic venous pressure gradient (HVPG) levels in a subgroup of subjects from the two treatment groups with the available data.
12. To score, in paired liver biopsies, the Metavir and Ishak - fibrosis score and histological index at the end of the study in the 2 treatment groups.
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Main Objective: To compare throughout the study the efficacy of PEG-Intron® monotherapy versus standard supportive care, using the time to the first occurrence of any one of the following clinical events (death, liver decompensation, liver transplant, hepatocellular carcinoma), in the two treatment groups .
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date:
Contact:
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