First in Human Study of ALS-002158; Single Dose, Food Effect in Healthy Volunteers; Multiple Doses in Chronic Hepatitis C Genotype 1

A Randomized, Double-blind, Placebo-controlled, First-in-human, 3-Part Study of Orally Administered ALS-002158 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dosing and Food-effect in Healthy Volunteers, and Multiple Ascending Dosing in Subjects With Chronic Hepatitis C Genotype 1 Infection

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.

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.