Treatment Naïve, Genotype 1 and 4, Chronic Hepatitis C Patients MedDRA version: 18.0 Level: LLT Classification code 10076315 Term: Hepatitis C virus genotype 4 positive System Organ Class: 100000004848 MedDRA version: 18.0 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. Both males and females of age 18 to 65 (inclusive) infected with one of the HCV genotype 1 or 4; 2. 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 Chronic Hepatitis C (CHC), including: • Previous documentation of positive HCV serology (HCV antibody or HCV RNA) at least 24 weeks prior to enrollment, 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. HCV treatment-naïve; 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 within normal limits (except for clearly documented Gilbert’s Syndrome) • ALAT 60 mL/min 6. All women of childbearing potential must have a negative serum pregnancy test at Screening. They should be using or willing to use a highly effective method of birth control: diaphragm, condom (by the partner), copper intrauterine device (or hormonal), sponge, or spermicide, and hormonal contraceptives. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, s.c., intrauterine, or intramuscular agents). Reliable contraception should be maintained from the Screening, throughout the whole study (W53); 7. Male subjects must agree to use birth control (condoms) from the time of dosing until 90 days after the Treatment Period; male subjects who are surgically sterile need not employ a method of contraception; 8. Negative results on the screening alcohol saliva test. Subjects should be able and willing to limit the alcohol intake to a maximum of 5 units per week during the whole study period (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits); 9. Negative results on the following screening laboratory tests: urine drug screen [opiates, cocaine, heroin, amphetamines (including ecstasy), barbiturates, benzodiazepines, tricyclic antidepressants; exceptions are cannabinoids and methadone], HBsAg, and HIV antibody; 10. Willingness to sign the ICF and obvious ability (mental and physical) to adhere to all study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 53 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
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, fibrosis 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: cardiac disease (unstable angina, myocardial infarction, congestive heart failure, or ventricular arrhythmia); cancer; uncontrolled seizure disorder; esophageal bleeding; ascites; chronic infection other than HCV (e.g., tuberculosis); uncontrolled diabetes; 6. Fibrosis scan score > F4 at Screening or within past 6 months; 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. Nursing females; 14. Any surgical procedure requiring general anesthesia planned to occur during the study period; 15. 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 10 months prior to Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of 2 mg/kg RG-101 when given in combination with oral agents for 28 days in HCV genotype 1 and 4 subjects in terms of change in viral load at Week 17 (12 weeks post treatment).;Secondary Objective: • To assess the efficacy of 2 mg/kg RG-101 when given in combination with oral agents in HCV genotypes 1 and 4 in terms of change in viral load at Week 29 (24 weeks post treatment) and Week 53 (48 weeks post treatment); • To assess the safety and tolerability of RG-101 when given in combination with oral agents in HCV genotypes 1 and 4; • To assess the time to viral load clearance in each of the genotypes and treatment arms. ;Primary end point(s): For each treatment arm within Cohorts 1 and 2 the proportion of subjects (90% Clopper-Pearson CI) attaining SVR12 will be estimated. ;Timepoint(s) of evaluation of this end point: Week 17 (12 weeks post treatment, SVR12) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Viral load related • Proportion of subjects with SVR at Week 29 (24 weeks post treatment, SVR24) and Week 53 (48 weeks post treatment, SVR48) in HCV genotypes 1 and 4; • 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 Week 53 (48 weeks post treatment, SVR48) or early termination; • Change in viral loads across visits. Biochemical response related • Changes in liver enzymes during the study course. Morphological responses • Changes from baseline in fibroscan values at the study end or early termination. Exploratory endpoints: • Changes from baseline in Patient Reported Outcomes (PRO) as measured through 3 different PRO instruments: o Short Form-36 version 2 (SF-36v2) o Chronic Liver Disease Questionnaire for Hepatitis (CLDQ-HCV) o The Functional Assessment of Chronic Illness (FACIT-F) Pharmacokinetic endpoints • Trough and other post-distribution phase concentrations of RG-101 related moieties [RG1649 (consisting of RG1649 and/or RG1649A), RG2459 (consisting of RG2459 and/or its GalNAc-on metabolites), and/or a combined concentration of RG1649 and RG2459]. ;Timepoint(s) of evaluation of this end point: Week 29 (24 weeks post treatment, SVR24) and Week 53 (48 weeks post treatment, SVR48), during the study course and at the study end or early termination. | — |
Countries
Greece, Hungary, Lebanon, Russian Federation, Serbia
Contacts
Public ContactClinical Trials Info
Accelsiors CRO and Consultancy Services Ltd
Outcome results
None listed