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

Hepatitis C, Chronic Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01554085
• Other study ID #: ALS-2158-201
• Status: Terminated
• Phase: Phase 1
• First received: March 12, 2012
• Last updated: October 27, 2017
• Start date: December 31, 2011
• Est. completion date: September 30, 2012

Study information

• Verified date: October 2017
• Source: Alios Biopharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 78
• Est. completion date: September 30, 2012
• Est. primary completion date: September 30, 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• ALS-002158
ALS-002158
• Placebo
placebo

Locations

Country	Name	City	State
Australia	CMAX	Adelaide	South Australia
Australia	QPharm	Brisbane	Queensland
Australia	Linear Clinical Research Ltd	Perth	Western Australia
New Zealand	Auckland Clinical Services	Auckland
New Zealand	Christchurch Clinical Studies Trust Ltd.	Christchurch

Sponsors (2)

Lead Sponsor	Collaborator
Alios Biopharma Inc.	Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	HCV ribonucleic acid (RNA) viral load reduction		Baseline to Day 31
Secondary	Sequence analysis of the Hepatitis C virus (HCV) NS5B region		Baseline up to Month 6