Hepatitis C, Chronic
Conditions
Brief summary
This randomized, double-blind, placebo-controlled, 3-part study will assess the safety, tolerability, and pharmacokinetics of orally administered ALS-002158 in healthy volunteers (HV) and subjects with chronic hepatitis C (CHC) genotype 1 infection. Part 1 will assess single ascending dosing pharmacokinetics and safety in HV. Part 2 will assess food effects on pharmacokinetics in HV. Part 3 will assess multiple ascending dosing pharmacokinetics and safety in subjects with CHC genotype 1 infection.
Interventions
DRUGALS-002158
ALS-002158
DRUGPlacebo
placebo
Sponsors
Vertex Pharmaceuticals Incorporated
Alios Biopharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject has provided written consent. * Subject is in good health as deemed by the investigator * Creatinine clearance of greater than 50 mL/min (Cockcroft- Gault). * Male or female, 18-55 years of age for HV and 18-65 years of age for subjects with CHC. * Body mass index (BMI) 18-32 kg/m2 inclusive for HV and 18-36 kg/m2 for subjects with CHC, minimum weight 50 kg in both populations. * A female is eligible to participate in this study if she is of non-childbearing potential. * If male, subject is surgically sterile or practicing specific forms of birth control. Additional inclusion criteria for subjects with CHC genotype 1 infection: * Positive HCV antibody and a positive HCV RNA at screening. * Documentation of CHC infection of greater than 6 months duration at screening. * CHC genotype 1 infection at screening. * HCV RNA viral load ≥ 105 and ≤ 108 IU/mL using a sensitive quantitative assay * Liver biopsy within two years or Fibroscan evaluation within 6 months prior to screening that clearly excludes cirrhosis. Fibroscan liver stiffness score must be \< 12 kPa. * Absence of hepatocellular carcinoma as indicated by an abdominal ultrasound scan during screening. * No prior treatment for CHC. * Absence of history of clinical hepatic decompensation. * Laboratory values include: * prothrombin time \< 1.5 × ULN. * platelets \> 120,000/mm3. * albumin \> 3.5 g/dL, bilirubin \< 1.5 mg/dL at screening (subjects with documented Gilbert's disease allowed). * Serum ALT concentration \< 5 × ULN. * Alpha Fetoprotein (AFP) concentration ≤ ULN. If AFP is ≥ ULN, absence of a hepatic mass must be demonstrated by ultrasound within the screening period.
Exclusion criteria
* Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid, or any uncontrolled medical illness or psychiatric disorder. * Positive test for HAV IgM, HBsAg, HCV Ab (HV only), or HIV Ab. * Abnormal screening laboratory results that are considered clinically significant by the investigator. * Clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, including those experienced in previous trials with experimental drugs. * Participation in an investigational drug trial or having received an investigational vaccine within 30 days or 5 half lives (whichever is longer) prior to receiving study medication. * Clinically significant blood loss or elective blood donation of significant volume. * Laboratory abnormalities including: * Thyroid Stimulating Hormone (TSH) \>ULN. * Hematocrit \< 34 %. * White blood cell counts \< 3,500/mm3. * For healthy volunteers, history of regular use of tobacco. * The subject has a positive pre-study drug screen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tabulation of adverse events, physical exam, vital signs, 12-lead ECGs, and clinical lab results | Part 1: Day 1-8; Part 2: Day 1-16; Part 3: Day 1-31 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters and urinary excretion of ALS-002158 and metabolites | Part 1: Day 1-8; Part 2: Day 1-16; Part 3: Day 1-31 | Maximum measured drug concentration (Cmax), time of maximum concentration (tmax), half-life (t1/2), apparent oral clearance (CL/F), area under the concentration time curve from time zero to infinity (AUC0-inf) or area under the concentration time curve from time zero to last quantifiable concentration (AUC0-last), area under the concentration time curve during the dosing interval (AUC0-tau) |
| HCV ribonucleic acid (RNA) viral load reduction | Baseline to Day 31 | — |
| Sequence analysis of the Hepatitis C virus (HCV) NS5B region | Baseline up to Month 6 | — |
Countries
Australia, New Zealand
Outcome results
None listed