Clinical trial NCT02371408 (phase 2/phase 3, status: unknown status)
Conditions: chronic hepatitis c
ICD codes: B18.2, B18.0, B18.1, B18.8, B18.9, K71.3, K71.4
Drugs: ravidasvir hydrochloride, sofosbuvir, ribavirin
SMILES: CC(C)OC(=O)[C@H](C)N[P@](=O)(OC[C@H]1O[C@@H](N2C=CC(=O)NC2=O)[C@](C)(F)[C@@H]1O)OC1=CC=CC=C1, NC(=O)C1=NN(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Eligibility criteria:

        Inclusion Criteria:

          1. Males or females, ≥ 18 years & ≤ 65 years of age.

          2. HCV antibody positive, with serum HCV RNA ≥ 10,000 IU/mL, with clinical history
             compatible with chronic hepatitis C.

          3. HCV genotype-4 infection, confirmed at the central study laboratory

          4. Body mass index (BMI) between 18 and 35 kg/m2, inclusive.

          5. Both male and female patients who have childbearing potential must agree to practice
             an acceptable method of birth control during the study and for at least 6 months after
             the cessation of treatment; such contraceptive methods must include at least one
             barrier method.

          6. Patients for Group 1 must be treatment-naïve - i.e., they have never received any
             antiviral treatment for their HCV infection, including interferon, pegylated
             interferon, ribavirin, or other regulatory-approved or investigational HCV antiviral
             therapies.

          7. Patients for Groups 2 and 3 must have previously failed treatment with an
             interferon-based therapy - i.e., interferon or pegylated interferon, with or without
             ribavirin, with no other previous HCV antiviral therapies.

             Patients for Group 2 must be non-cirrhotic diagnosed on screening visit by both
             Fibroscan™ liver stiffness measurement < 12.5 kPa and FIB-4 score < 3.25 if the
             results of Fibroscan and FIB-4 score are not matching; liver biopsy will be used for
             detection of cirrhosis. In case that the liver biopsy is not applicable, hepatic
             imaging or ultrasound reports could be used for determination of cirrhosis.

             Patients for Group 3 must have underlying cirrhosis diagnosed on screening visit by
             both Fibroscan liver stiffness measurement > 12.5 kPa and FIB-4 score > 3.25, if the
             results of Fibroscan and FIB-4 score are not matching liver biopsy will be used for
             detection of cirrhosis. In case that the liver biopsy is not applicable, hepatic
             imaging or ultrasound reports could be used for determination of cirrhosis.

          8. Willing and able to give informed consent

          9. Willing and able to complete all study visits and procedures, including compliance
             with the requirements and restrictions listed in the consent form.

        Exclusion Criteria:

          1. Mixed genotype or non-typable HCV genotype infection,

          2. Positive test for HBsAg or HIV antibody, or IgM antibody to HAV or HEV

          3. History of schistosomiasis or positive test for schistosoma surface antigen at Screen.

          4. Serum alpha-fetoprotein (AFP) >100ng/ml. Patients with an AFP between 50 and 100ng/ml
             may be included as long as a liver ultrasound within 3 months of Screening, or at
             Screening, shows no evidence of potential hepatocellular cancer.

          5. History of treatment with any investigational or regulatory-approved direct-acting
             antiviral (DAA) agent for HCV infection - nucleos(t)ide or non-nucleosidic HCV
             polymerase inhibitor, HCV protease inhibitor, NS5A inhibitor, or other antiviral agent
             for HCV infection other than pegylated -interferon and/or ribavirin Previous pegylated
             interferon and/or ribavirin treatment is allowed for Groups 2 and 3 but prohibited for
             group 1, as noted above in Inclusion criterion 6)

          6. Evidence of a medical condition other than HCV that is contributing to liver disease

          7. History of, or clinical signs of, hepatic decompensation or portal hypertension:

             Variceal bleeding, or documented esophageal or GI varices (at investigator discretion,
             patients suspected of having esophageal varices should be evaluated by endoscopy, and
             varices excluded) Ascites by history or on physical examination Documented or
             suspected hepatic encephalopathy

             Physical signs of portal hypertension:

             Clinically significant splenomegaly Spider angiomata History of porto-systemic shunt
             procedure(s)

          8. Uncontrolled diabetes mellitus as evidenced by HgbA1C ≥ 8.5% at Screening.

          9. Hemoglobin < 11g/dL for females and < 12 g/dL for males

         10. WBC count < 3,500/mm3 OR absolute neutrophil count (ANC) < 1800/mm

         11. Platelet count < 75,000/mm3

         12. Serum creatinine > 1.3 x ULN OR creatinine clearance (GFR) < 50 mL/minute

         13. Serum ALT or AST >10x ULN

         14. Serum albumin ≤ 3.2 g/dl

         15. Direct serum bilirubin > 2xULN

         16. INR > 1.7.

         17. History of poorly controlled asthma, with one or more hospitalizations or emergency
             room visits in the previous 6 months

         18. History of any malignancy within the last 5 years (except prostate cancer still within
             Glisson's capsule or basal cell carcinoma of the skin).

         19. History of alcohol abuse as assessed by the investigator within the past 2 years, or
             an alcohol use pattern that may interfere with the patient's study compliance.
             Patients must have abstained from alcohol for at least 6 months prior to study start.

         20. History of drug abuse as assessed by the investigator within the last 2 years.

         21. Pregnancy, including current lactation in female patients, male patients with partners
             who are pregnant, or female patients intending to become pregnant.

         22. Major surgery requiring overnight hospitalization within 3 months prior to Screening

         23. Participation in another clinical trial of an investigational drug or device within 6
             months prior to Screening

         24. Current use or history of use within the preceding 6 months of immunosuppressive or
             immune-modulating agents, including: azathioprine, systemic corticosteroids
             (prednisone or prednisone equivalent of more than 10mg/day for more than 10 days), or
             other immunosuppressive agents. Use of inhaled steroids for mild/moderate asthma and
             topical steroids for minor skin conditions is allowed.

         25. History of solid organ or bone marrow transplantation.

         26. History of use of medications associated with QT prolongation concurrently or within
             the 30 days prior to Screening Visit, including: macrolides, antiarrhythmic agents,
             azoles, fluoroquinolones, and tricyclic anti-depressants.

         27. correction, or a personal or family history of Torsades de Pointe.

         28. Cardiac ischemia with history of recurrent angina, clinically symptomatic cardiac
             abnormalities, or requirement for cardiac pacemaker

         29. History of a known allergy to ribavirin (RBV), or any excipient in the investigational
             product, or history of drug or other allergy that, in the opinion of the investigator,
             mitigates against study participation