Efficacy and Safety of PEG-Intron plus Rebetol in Subjects with Chronic Hepatitis C Genotype 1 Non Responder to Pegasys - Non-Responder Study

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2004-001220-20-GB
• Date of registration: 26/04/2005
• Prospective Registration: Yes
• Primary sponsor: Integrated Therapeutics Group, Incorporated - a subsidiary of Schering-Plough
• Public title: Efficacy and Safety of PEG-Intron plus Rebetol in Subjects with Chronic Hepatitis C Genotype 1 Non Responder to Pegasys - Non-Responder Study
• Scientific title: Efficacy and Safety of PEG-Intron plus Rebetol in Subjects with Chronic Hepatitis C Genotype 1 Non Responder to Pegasys - Non-Responder Study
• Date of first enrolment: 23/09/2005
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001220-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1) Subject must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
2) Subject must be 18 – 70 years of age of either sex and of any race.
3)Subject must be diagnosed with chronic hepatitis C genotype 1 (confirmation by biopsy not required. LFTs can be normal or elevated)
4) Female subjects cannot be pregnant or breastfeeding and must be either postmenopausal, surgically sterile or using 2 methods of birth control. While abstinence from sexual activity is the only certain method to prevent pregnancy, female patients of childbearing potential who are or who anticipate the possibility of becoming sexually active with a male partner must use a combination of the following 2 methods :
(a) contraceptive pill or IUD or depot hormonal preparation (ring, injection implant) and
(b) a barrier method of contraception such as diaphragm, sponge with spermicide, condom, or a method of birth control considered acceptable by the study physician.
Contraceptive measures will be reviewed with female subjects at each visit. Dual methods of contraception must be used for 6 months after treatment discontinuation.
5) Female subjects of childbearing potential must have a negative serum pregnancy test at screen phase and during the study.
6) Confirmation by the principal investigator or a sub-investigator that sexually active male subjects are practicing a method of contraception considered acceptable (vasectomy, condom plus spermicide, plus relationship with a female partner who practices an acceptable method of contraception). Contraception must be used during the treatment period and for seven months after the completion of therapy, including condom use by male subjects with pregnant partners
7) Subject must be free of any clinically significant disease that would interfere with study evaluations.
8) Subject must understand, be able to and agree to adhere to the dosing and visit schedules.
9) Compensated liver disease with the following minimum hematologic and biochemical criteria at the Day 1 visit within normal limits:
• Hemoglobin values of equal to or more than12 gm/dL for females and 13 g/dL for males.
• WBC equal to or more than 3,000/mm3
• Neutrophil count equal to or more than 1,500/mm3
• Platelet count equal to or more than 80,000/mm3
• Direct bilirubin within normal limits
• Indirect bilirubin within normal limits (unless non-hepatitis related factors such as Gilbert's disease explain an indirect bilirubin rise). In such cases indirect bilirubin should be less than or equal to 3.0 mg/dL (less than or equal to 51.3 µmol/L)
• Albumin within normal limits
• Serum creatinine within normal limits
• Subject must be a non-responder, defined as having received and not having responded to a prior treatment consisting of one course of Pegasys 180 mcg QW in combination with ribavirin 1000-1200 mg daily, with or without amantadine, for a minimum of 12 weeks and:
(a) Subject must be found to be HCV-RNA positive with less than a 2 log drop at 12 weeks of treatment
or
(b) is PCR po
Exclusion criteria:
1. Subject is a female who is pregnant or breastfeeding, or who intends to become pregnant during the study.
2. Subject has used any investigational product within 30 days prior to enrollment or is currently involved in another clinical trial.
3. Subjects weighing over 125 kg.
4. Subject has any of the following causes for the liver disease based on subject history or biopsy (where applicable) other than chronic hepatitis C, including but not limited to:
• hemochromatosis
• alpha-1 antitrypsin deficiency
• Wilson’s disease
• autoimmune hepatitis
• alcoholic liver disease
• non-alcoholic steatohepatitis (NASH)
• drug related liver disease

5. Subject has any clinically significant deviation from normal in the physical examination, Chest X-ray, or ECG that, in the investigator’s judgment, may interfere with the study evaluation or affect subject safety.
6. Subject is in a situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
7. Subject is part of the staff or a family member of the staff personnel directly involved with this study.
8. Subject is a previously untreated subject
9. Subject has been treated with Pegasys + less than 1000 mg of ribavirin (instead of with 1000–1200 mg of ribavirin)
10. Subject has been discontinued from Pegasys treatment at any week due to an adverse event.
11. Subject is co-infected with HIV and/or HBV
12. Subject is suspected to be hypersensitive to interferon alpha or Peg-Intron or ribavirin
13. Subject has previously received interferon, (except for the Pegasys flat dose 180 mcg QW for at least 12 weeks), thymosin or Cell Cept treatment or any other drug intended to treat chronic hepatitis C
14. Subject has had organ transplants other than cornea and hair transplant.
15. Subject has a history of hepatocellular carcinoma or any other malignancy (except Basal Cell Carcinoma) within the last 5 years or a suspected diagnosis of hepatocellular carcinoma or other malignancy, or an active malignancy.
16. Known coagulation diseases such as hemophilia; hemoglobin diseases (e.g. thalassemia)
17. Subject has G6PD deficiency
18. Subject has an evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy.
19. Subject has any known pre-existing medical condition that could interfere with the subject’s participation in and completion of the study as followed below:
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:
? hospitalization for depression
? electroconvulsive therapy for depression, or
? 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 emotio

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Hepatitis C, Genotype 1

Intervention(s)

Trade Name: PegIntron
Product Name: Pegintron
Product Code: SCH 54031
Pharmaceutical Form: Injection*
INN or Proposed INN: peginterferon alfa-2b
CAS Number: 215647-85-1
Current Sponsor code: SCH 54031
Other descriptive name: PegIntron
Concentration unit: µg microgram(s)
Concentration type: range
Concentration number: 50-150

Trade Name: Rebetol
Product Name: Rebetol
Product Code: SCH 18908
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ribavarin
Current Sponsor code: SCH 18908
Other descriptive name: Rebetol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: The objective of this study is to determine the proportion of chronic hepatitis C genotype 1 subjects who did not respond to previous treatment with Pegasys 180µg QW plus ribavirin, that will achieve sustained virological response (SVR) when treated with PEG-Intron plus REBETOL.

Primary end point(s): Proportion of subjects who have achieved sustained virological response at 24 weeks post end of treatment

Secondary Objective: The secondary objectives are to assess the efficacy of PEG-Intron plus Rebetol for early virological response (EVR) at 12 weeks of treatment and response rate at the end of treatment (EOT) at 48 weeks of treatment. Also, there will be a subgroup analysis of subjects by SVR according to high/low viral load, presence of cirrhosis; SVR according to insulin resistance status and SVR according to creatinine clearance Cystatin C status.

Secondary ID(s)

P03833

2004-001220-20-AT

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 02/06/2016
• Date Completed: 23/06/2008
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-001220-20/results