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-002200 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-002200
ALS-002200
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. * In the investigator's opinion, the subject is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned. * 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 for greater than 6 months 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 ultrasound scan conducted during screening * No prior treatment for CHC * Absence of history of clinical hepatic decompensation. * Laboratory values include: * Prothrombin time \< 1.5x 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 alanine aminotransferase (ALT) concentration \< 5 x ULN * Alpha Fetoprotein (AFP) concentrations ≤ 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. * 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 study medication. * Clinically significant blood loss or elective blood donation of significant volume. * For healthy subjects, history of regular use of tobacco. * The subject has a positive pre-study drug screen. * Laboratory abnormalities including: * Thyroid Stimulating Hormone (TSH) \> ULN * Hematocrit \< 34 % * White blood cell counts \< 3,500/mm3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | up to Day 31 | data points measured include patient reported adverse events, physical exams, vital signs, 12-lead ECGs and clinical lab results |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 240 hours post dose | — |
| AUC | pre-dose and 0.25, 0.5, 1, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 240 hours post dose | — |
| HCV ribonucleic acid (RNA) viral load reduction | Baseline to Day 31 | — |
| Amino Acid Changes in HCV polymerase NS5b | Baseline up to Month 6 | Comparison of baseline with on-treatment or post-treatment Hepatitis C virus (HCV) NS5B RNA sequence |
Countries
France, Moldova, Romania
Outcome results
None listed