Treatment Naïve, Genotype 1 and 3, Chronic Hepatitis C Patients MedDRA version: 19.0 Level: LLT Classification code 10076831 Term: Chronic hepatitis C genotype 3 System Organ Class: 100000004862 MedDRA version: 19.0 Level: LLT Classification code 10074391 Term: Chronic hepatitis C virus genotype 1 System Organ Class: 100000004862
Conditions
Sponsors
Regulus Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adults aged 18 to 75 (inclusive) infected with HCV genotype 1 or 3; 2. Body mass index (BMI): 18.0 – 35.0 kg/m2; [BMI (kg/m2) = Body weight (kg) ÷ Height2 (m2)]; 3. Clinical and laboratory findings consistent with a clinical diagnosis of CHC, including: • Previous documentation of positive HCV serology (HCV antibody or HCV RNA) at least 24 weeks prior to enrolment, or • Positive HCV serology (HCV antibody or HCV RNA) less than 24 weeks with a prior remote risk factor (more than 24 weeks prior to Screening) for the acquisition of hepatitis C, and • Serum HCV RNA = 375,000 copies/mL or = 75,000 IU/mL at Screening; 4. Subjects must have been treatment-naïve and had not received prior treatment with any interferon, immunomodulatory agent, or direct acting antiviral agent (DAA) or ribavirin containing regimen for HCV; 5. Screening hematology, clinical chemistries, coagulation and urinalysis are not clinically significant and the following criteria are met: • Platelets > 100x109/L • Total white blood cells > 3.0x109/L and absolute neutrophil count > 1.5x109/L • Hemoglobin > 10.95 g/dL for females and > 11.92 g/dL for males • Total and direct bilirubin 60 mL/min. Cockroft-Gault formula: ((140 – age) x weight (in kilograms) x constant) / serum creatinine (in µmol/L), where constant is 1.23 for men and 1.04 for women Note: At the discretion of the Investigator, screening laboratory testing may be repeated once to confirm out of-range (exclusionary) results. 6. Female subjects must be of non-childbearing potential and must have undergone one of the following sterilization procedures at least 6 months prior to dosing: a. hysteroscopic sterilization; b. bilateral tubal ligation or bilateral salpingectomy; c. hysterectomy; d. bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status as per Investigator judgment; 7. Male subjects with female partners of childbearing potential must use one of the following contraception methods from the time of the first dose of study medication to the last follow-up visit in the Short Term Follow-up Period (12 weeks after the last dose of study medication): a. Male condom plus partner use of one of the following highly effective contraceptives: • Contraceptive subdermal implant; • Intrauterine device (IUD) or intrauterine system (IUS); • Combined estrogen and progestogen oral contraceptive; • Injectable progestogen; • Contraceptive vaginal ring; • Percutaneous contraceptive patches; b. Documented sterilization of the male subject. For this definition, “documented” refers to the outcome of the Investigator's/designee’s review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records; c. Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; 8. Negative results on the screening alcohol saliva
Exclusion criteria
Exclusion criteria: 1. Other known cause of liver disease except for CHC; 2. History or symptoms of decompensated liver disease: Child-Pugh Class B or C, including ascites, hepatic encephalopathy, esophageal variceal bleeding, cirrhosis, or other signs of hepatic insufficiency or portal hypertension; 3. History of hepatocellular carcinoma or current liver mass consistent with malignancy on imaging studies; 4. Serum alpha-fetoprotein (AFP) > 50 ng/mL at Screening; 5. Concurrent clinically significant medical diagnosis (other than hepatitis C-related conditions) that would potentially interfere with the subjects study compliance or confound study results including but not limited to: significant or unstable cardiac disease (e.g., prolonged QT syndrome [torsades de pointe], unstable angina, myocardial infarction, diastolic dysfunction, congestive heart failure, significant arrhythmia, coronary heart disease, and/or clinically significant ECG abnormalities); cancer; uncontrolled seizure disorder; ascites; chronic infection other than HCV (e.g., tuberculosis); uncontrolled diabetes, and/or uncontrolled thyroid disease; 6. Evidence of cirrhosis, as determined by any one of the following: a. FibroSure/FibroTest score >0.58 or Fibroscan score indicative of cirrhosis (=14.5 kPa); or b. Liver biopsy with a fibrosis stage indicative of cirrhosis as classified by a local pathologist (defined as Knodell > 3, Metavir > 2, Ishak > 4, or Batts and Ludwig > 2). Both incomplete and transition to cirrhosis (e.g., Metavir score 3) are considered as cirrhosis; or c. History of ascites, hepatic encephalopathy, or esophagogastric varices; 7. Concurrent social conditions (e.g., drugs, alcohol) which would potentially interfere with the subject’s study compliance; 8. Use of anticonvulsants, antimycobacterials, analeptics and herbal supplements that may interact with the bioavailability of the investigational product or oral DAA agents; or other alternative medicines that may have influence on the disease outcome; 9. Mental handicap or history of or current significant psychiatric disease (which might impair ability to provide informed consent); 10. Clinically significant illness within 30 days prior to Screening; 11. Have used an investigational drug or has participated in an investigational study with a licensed drug within 30 days or 5 half lives, whichever is longer, prior to study drug administration; 12. History of relevant drug and/or food allergies; 13. Donation of more than 500 mL of blood within 60 days prior to drug administration. Donation of more than 1.5 liters of blood (for men) / more than 1.0 liter of blood (for women) in the 6 months prior to Screening; 14. The following family history of cardiac disease: • prolonged QT syndrome (Torsade de Pointes) or sudden cardiac death; • first-degree relative with myocardial infarction at premature age (= 45 years for male relative; = 55 years for female relative); 15. Evidence of clinically significant pulmonary disease, as determined by any of the following: a. Known (past or current) history of significant asthma, emphysema, chronic obstructive pulmonary disease, and/or interstitial lung disease; or b. Abnormal pretreatment spirometry results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To assess the safety and tolerability of RG-101 when given in combination with oral GSK2878175 taken for 6, 9, or 12 weeks in subjects with HCV genotypes 1 and 3; • To assess the efficacy of a single injection of 4 mg/kg RG-101 when given in combination with oral GSK2878175 20 mg/day taken for 6, 9, or 12 weeks in subjects with HCV genotypes 1 and 3, in terms of proportion of subjects with sustained virologic response at 24 and 48 weeks after end of treatment (SVR24 and SVR48, respectively) with GSK2878175; • To assess the time to viral load clearance in each of the genotypes and treatment arms; • To assess plasma concentrations or pharmacokinetics (PK) of GSK2878175 and RG-101 related moieties [unconjugated (consisting of RG1649 and/or RG1649A), conjugated (consisting of RG2459 and/or its N acetylgalactosamine [GalNAc]-on metabolites), and/or a total combined concentration of unconjugated and conjugated moieties] at selected sampling time points only. ;Primary end point(s): Proportion of subjects with SVR12 in HCV genotypes 1 and 3;Timepoint(s) of evaluation of this end point: Week 12 ;Main Objective: To assess the efficacy of a single subcutaneous (s.c.) injection of 4 mg/kg RG-101 when given in combination with oral GSK2878175 20 mg/day taken for 6, 9, or 12 weeks in subjects with hepatitis C virus (HCV) genotypes 1 and 3, in terms of proportion of subjects with sustained virologic response (SVR) at 12 weeks after end of treatment (SVR12) with GSK2878175. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Viral load related • Proportion of subjects with SVR24 and SVR48 in HCV genotypes 1 and 3; • Time to viral load clearance in each of the genotypes and treatment arms; • Proportion of relapsed subjects in each HCV genotype; • Proportion of non-responders and partial responders; • Proportion of subjects with viral resistance development at 48 weeks post end of GSK175 treatment or early termination; • Change in viral loads across visits. Biochemical response related • Changes in liver enzymes during the study course; • Changes in lipid profile during the study course; • Changes in hematology and blood chemistry. Pulmonary safety related • Changes in pulmonary function. Pharmacokinetic and pharmacokinetic/pharmacodynamic endpoints • Measured plasma concentrations or PK of RG-101 related moieties [unconjugated (consisting of RG1649 and/or RG1649A), conjugated (consisting of RG2459 and/or its GalNAc-on metabolites), and/or a total combined concentration of unconjugated and conjugated moieties] at selected sampling time points; • Measured plasma concentrations or PK of GSK2878175.;Timepoint(s) of evaluation of this end point: Week 12, week 24, week 48 | — |
Countries
Greece, Hungary, Serbia, Spain
Contacts
Public ContactClinical Trials Info
Accelsiors CRO and Consultancy Services Ltd
Outcome results
None listed