Back to resultsClinical Trial to Assess Safety and Efficacy of Combination Therapy: Hydroxychloroquine, Pegylated Interferon Alpha-2a and Ribavirin in Chronic Hepatitis C Subjects Non-responders to the Standard of Care Therapy.
Primary Purpose
Chronic Hepatitis C
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (Peg-IFN alpha-2a) and Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Chronic Hepatitis C, Combination Therapy, Hydroxychloroquine, Pegylated Interferon Alpha-2a, Ribavirin, Chronic Hepatitis C Genotype 1 infected adult subjects
Eligibility Criteria
Inclusion Criteria:
- Males and females between 18 and 70 years old.
- Subjects diagnosed to have positive HCV antibodies using a third generation test.
- Subject is diagnosed to have detectable HCV RNA by PCR.
- Liver biopsy or FibroTest showing a METAVIR score ≥F2 and/or ≥A2.
- Subject diagnosed to have compensated liver disease.
- Subject is non-responder (null or partial) on prior Peg-IFN and RBV based treatment lasting for at least 12 consecutive weeks.
- Treatment not discontinued due to intolerability to Peg-IFN or RBV.
- Subjects able to comprehend and give informed consent for participation in this study.
- Subject is willing to be treated and commit to all visits.
Exclusion Criteria:
- Anti HCV therapy contraindications.
- Subject is identified as a relapser on prior Peg-IFN and RBV based treatment.
- Hypersensitivity to one of the three drugs (HCQ, Peg-IFN, RBV).
- Patient has Anaemia,neutropenia, thrombocytopenia, elevated bilirubin levels, elevated ALT and/or AST, or elevated creatinin and INR greater than 1.5.
- Concomitant liver disease other than hepatitis C: chronic hepatitis B, alcoholic liver disease, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency.
- Decompensated cirrhosis (Child Pugh >A).
- Clinical evidence for hepatocellular carcinoma.
- Human immunodeficiency virus co-infection.
- Major uncontrolled psychiatric illness. Minor or situational depressions are allowed.
- Active elicit drug or alcohol abuse.
- Serious co-morbid conditions as: heart failure, significant coronary heart disease, chronic obstructive pulmonary disease, renal insufficiency, poorly controlled diabetes, autoimmune disorders, and malignant diseases in the previous 5 years.
- Immunosuppressive treatment including corticosteroids,
- Untreated or uncontrolled or thyroid disease.
- Solid transplant organ (renal, heart, or lung).
- Pregnancy or unwillingness to practice double contraception or abstinence by the subject of childbearing potential or partner.
- Subject objects to the study protocol.
- Concurrent participation in any other clinical study within 30 days prior to enrollment.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Combination therapy
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline in physical examination
Body system screaning
Change from baseline in vital Signs
Heart Rate, Blood Presure, Respiratory Rate , Body temperature
Change from baseline in clinical laboratory parameters
Hematology, Blood Chemistry, Coagulation parameters, Urinalysis
Change from baseline in adverse events
All observed and or reported adverse events
Secondary Outcome Measures
HCV RNA level
Changes in HCV RNA levels, monitored along the study period. The efficacy of a HCQ-containing treatment regimen defined as the proportion of subjects with SVR i.e. undetectable HCV RNA <50 IU/ml) at 5 different time points: cEVR at 12 weeks, 4 weeks, 24 weeks, 48 weeks after treatment initiation and at 24 weeks after end of treatment (week 72).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01272310
Brief Title
Clinical Trial to Assess Safety and Efficacy of Combination Therapy: Hydroxychloroquine, Pegylated Interferon Alpha-2a and Ribavirin in Chronic Hepatitis C Subjects Non-responders to the Standard of Care Therapy.
Official Title
A Phase I/II, Open Clinical Trial to Assess the Safety, Tolerability and Efficacy of a Fixed Dose Combination Therapy of: Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (Peg-IFN Alpha-2a) and Ribavirin (RBV) in Chronic Hepatitis C Genotype 1 Infected Subjects Who Failed to Respond Following a Course of Peg-IFN and RBV Therapy (SoC).
Study Type
Interventional
2. Study Status
Record Verification Date
January 2011
Overall Recruitment Status
Unknown status
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2012 (Anticipated)
Study Completion Date
July 2013 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Sheba Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study is aimed to investigate the safety, tolerability and efficacy of a fixed dose combination therapy of: Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (PEG-IFN alpha-2a) and Ribavirin (RBV) in Chronic Hepatitis C Genotype 1 Infected adult subjects who failed to respond following a course of PEG-IFN and RBV Therapy.
Detailed Description
This is a phase I/II, open clinical trial to assess the safety, tolerability and preliminary efficacy data of a fixed dose combination therapy of: HCQ, Peg-IFN alpha-2a and RBV in chronic hepatitis C genotype 1 infected subjects who failed to respond following a course of Peg-IFN and RBV Therapy (SoC). The study is a single center trial to be conducted at the Department of Gastroenterology & Hepatology, at Sheba Medical Center, Tel Hashomer, Israel.
Overall, thirty six (36) patients will be recruited. All patients enrolled will have a documented history of chronic HCV disease and being non-responder on earlier Peg-IFN based treatment lasting for at least 12 consecutive weeks prior to study enrolment.
The expected duration of patient screening period prior to enrollment into this study is in-between six weeks (42 days) up to 2 days prior to the study enrollment day at visit 2 (verification of compliance with inclusion/exclusion criteria including clinical laboratory results). Eligible patients will be enrolled into the study and will be observed twice on the first week of the study, once a week during the initiation of the treatment period at weeks 2,3 and week 4, later during the treatment period once a month at weeks 8-48 and at two follow up visits post treatment to take place at week 60 and 72 (allowing a time window of ± 5 days for all visits).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
Chronic Hepatitis C, Combination Therapy, Hydroxychloroquine, Pegylated Interferon Alpha-2a, Ribavirin, Chronic Hepatitis C Genotype 1 infected adult subjects
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Combination therapy
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (Peg-IFN alpha-2a) and Ribavirin
Other Intervention Name(s)
Copegus, Pegasys
Intervention Description
HCQ will be taken daily as an oral tablet of 200 mg b.i.d. Pegylated Interferon Alpha-2a - (180 µg) will be administered as weekly subcutaneous (s.c.) injections of 0.5 ml.
Ribavirin - will be taken daily based on the patient body weight. If body weight is < 75 kg, the total daily dose of Copegus® is 1000 mg, administered as 400 mg (2 tablets of 200 mg, morning intake) and 600 mg (3 tablets of 200 mg, evening intake). If body weight is >= 75 kg, the total daily dose is 1200 mg administered as twice 600 mg (3 tablets of 200 mg per intake, morning and evening).
Primary Outcome Measure Information:
Title
Change from baseline in physical examination
Description
Body system screaning
Time Frame
Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
Title
Change from baseline in vital Signs
Description
Heart Rate, Blood Presure, Respiratory Rate , Body temperature
Time Frame
Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
Title
Change from baseline in clinical laboratory parameters
Description
Hematology, Blood Chemistry, Coagulation parameters, Urinalysis
Time Frame
Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
Title
Change from baseline in adverse events
Description
All observed and or reported adverse events
Time Frame
Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
Secondary Outcome Measure Information:
Title
HCV RNA level
Description
Changes in HCV RNA levels, monitored along the study period. The efficacy of a HCQ-containing treatment regimen defined as the proportion of subjects with SVR i.e. undetectable HCV RNA <50 IU/ml) at 5 different time points: cEVR at 12 weeks, 4 weeks, 24 weeks, 48 weeks after treatment initiation and at 24 weeks after end of treatment (week 72).
Time Frame
at 4,12, 24, 48 and 72 weeks after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females between 18 and 70 years old.
Subjects diagnosed to have positive HCV antibodies using a third generation test.
Subject is diagnosed to have detectable HCV RNA by PCR.
Liver biopsy or FibroTest showing a METAVIR score ≥F2 and/or ≥A2.
Subject diagnosed to have compensated liver disease.
Subject is non-responder (null or partial) on prior Peg-IFN and RBV based treatment lasting for at least 12 consecutive weeks.
Treatment not discontinued due to intolerability to Peg-IFN or RBV.
Subjects able to comprehend and give informed consent for participation in this study.
Subject is willing to be treated and commit to all visits.
Exclusion Criteria:
Anti HCV therapy contraindications.
Subject is identified as a relapser on prior Peg-IFN and RBV based treatment.
Hypersensitivity to one of the three drugs (HCQ, Peg-IFN, RBV).
Patient has Anaemia,neutropenia, thrombocytopenia, elevated bilirubin levels, elevated ALT and/or AST, or elevated creatinin and INR greater than 1.5.
Concomitant liver disease other than hepatitis C: chronic hepatitis B, alcoholic liver disease, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency.
Decompensated cirrhosis (Child Pugh >A).
Clinical evidence for hepatocellular carcinoma.
Human immunodeficiency virus co-infection.
Major uncontrolled psychiatric illness. Minor or situational depressions are allowed.
Active elicit drug or alcohol abuse.
Serious co-morbid conditions as: heart failure, significant coronary heart disease, chronic obstructive pulmonary disease, renal insufficiency, poorly controlled diabetes, autoimmune disorders, and malignant diseases in the previous 5 years.
Immunosuppressive treatment including corticosteroids,
Untreated or uncontrolled or thyroid disease.
Solid transplant organ (renal, heart, or lung).
Pregnancy or unwillingness to practice double contraception or abstinence by the subject of childbearing potential or partner.
Subject objects to the study protocol.
Concurrent participation in any other clinical study within 30 days prior to enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yaakov Maor, Dr
Phone
97235302906
Email
yaakov.maor@sheba.health.gov.il
12. IPD Sharing Statement
Learn more about this trial
Clinical Trial to Assess Safety and Efficacy of Combination Therapy: Hydroxychloroquine, Pegylated Interferon Alpha-2a and Ribavirin in Chronic Hepatitis C Subjects Non-responders to the Standard of Care Therapy.
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