Efficacy, Safety and Tolerability of Ribavirin Monotherapy Followed by Combined Treatment With Ribavirin and Hydroxychloroquine in Patients Infected With Hepatitis C

• Status: Terminated
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Proof-of Concept, Open-Label, Two-Stage Study without Direct Individual Benefit The proposed study design consists of two treatment periods and one treatment arm. Treatment Period 1 involves the administration of RBV monotherapy for a period of 8 weeks and Treatment Period 2 involves administration of up to 16 weeks combination therapy with RBV plus HCQ.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BioLineRx, Ltd.
• Treatments: Hydroxychloroquine; Ribavirin

Criteria

Inclusion Criteria:

1. Male or female, age ≥ 18.

2. Subjects diagnosed to have positive HCV antibodies.

3. Subject is diagnosed to have detectable HCV RNA by PCR.

4. FibroTest or FibroScan or liver biopsy showing a METAVIR score ≤ F2 and/or

≤ A2 within 2 years of the screening visit.

5. Subject is a non-responder (null or partial ) OR relapsed following prior Peg-IFN and RBV based treatment lasting for at least 12 consecutive weeks.

6. Platelet count greater than or equal to 100,000 cells/mm3.

7. Absolute neutrophil count (ANC) greater than or equal to 1500 cells/mm3.

8. Subjects able to comprehend and give written informed consent for participation in this study.

9. Women of childbearing potential and all men must agree to use an approved form of contraception (e.g., oral, transdermal patch, implanted contraceptives, intrauterine device, diaphragm, condom, abstinence or surgical sterility) prior to study entry and for the duration of study participation through 7 months after the last dose of study medication. Confirmation that the female patient is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

10. Subject is willing to be treated and commit to all visits

Exclusion Criteria:

1. Contraindication or hypersensitivity to one of the study drugs (HCQ or RBV).

2. Patient has anemia (male <13 g/dL; female <12 g/dL), elevated ALT and/or AST >10 x ULN or elevated creatinine (>1.5 mg/dL).

3. Concomitant liver disease other than hepatitis C: alcoholic liver disease, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency.

4. Decompensated cirrhosis (Child Pugh >A).

5. Ongoing hepatocellular carcinoma (suggestive imaging study or alpha-fetoprotein (AFP) >50 ng/mL).

6. Hepatitis B or Human Immunodeficiency Virus (HIV1 or HIV2) co-infection.

7. Clinically relevant ECG abnormalities on screening or baseline 12-lead ECG, e.g.,

• QTc interval (QTcB or QTcF > 450 ms in males and > 470 ms in females);

• Notable resting bradycardia (HR < 40 bpm);

• Any other significant abnormality suggestive of structural heart disease.

8. Family history of congenital long QT syndrome.

9. Clinically significant abnormalities on ophthalmic examination.

10. Major uncontrolled psychiatric illness. Minor or situational depressions are allowed.

11. History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to hemolysis (e.g., G-6-PD deficiency).

12. Active illicit drug or alcohol abuse.

13. Serious co-morbid conditions such as: heart failure, significant coronary heart disease, chronic obstructive pulmonary disease, poorly controlled diabetes, autoimmune disorders and any malignant diseases (except in situ carcinomas or basal cell carcinoma) in the previous 5 years.

14. Patients with chronic renal insufficiency, creatinine clearance < 50 mL/minute and/or undergoing haemodialysis.

15. Patients with porphyria or psoriasis.

16. Ongoing concomitant treatment with azathioprine, digoxin or medications known to prolong QT interval.

17. History of organ transplantation.

18. Pregnancy, breast-feeding or unwillingness to practice double contraception or abstinence by the subject of childbearing potential or partner.

19. Concurrent participation in any other clinical study or within 180 days 20.Patients with inability to communicate well with the Investigators and staff (i.e., language problem, poor mental development or impaired cerebral function) or any other condition that in the opinion of the Investigator will place the patient at risk or prevent protocol compliance.

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