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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Hepatitis C, Chronic

Intervention / Treatment
-----------------
* Drug: ALS-002158
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALS-002158<br> | Drug: ALS-002158<br>* ALS-002158<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters and urinary excretion of ALS-002158 and metabolites | 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) | Part 1: Day 1-8; Part 2: Day 1-16; Part 3: Day 1-31 | 
| 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 |