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

This study has been terminated.
(ALS-2158 showed insufficient antiviral activity to warrant proceeding with further clinical development.)
Sponsor:
Collaborator:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Alios Biopharma Inc.
ClinicalTrials.gov Identifier:
NCT01554085
First received: March 12, 2012
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: ALS-002158
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Alios Biopharma Inc.:

Primary Outcome Measures:
  • Tabulation of adverse events, physical exam, vital signs, 12-lead ECGs, and clinical lab results [ Time Frame: Part 1: Day 1-8; Part 2: Day 1-16; Part 3: Day 1-31 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters and urinary excretion of ALS-002158 and metabolites [ Time Frame: Part 1: Day 1-8; Part 2: Day 1-16; Part 3: Day 1-31 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Day 31 ] [ Designated as safety issue: No ]
  • Sequence analysis of the Hepatitis C virus (HCV) NS5B region [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]

Enrollment: 78
Study Start Date: December 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALS-002158 Drug: ALS-002158
ALS-002158
Placebo Comparator: Placebo Drug: Placebo
placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01554085

Locations
Australia, Queensland
QPharm
Brisbane, Queensland, Australia, 4006
Australia, South Australia
CMAX
Adelaide, South Australia, Australia, 5000
Australia, Western Australia
Linear Clinical Research Ltd
Perth, Western Australia, Australia, 6009
New Zealand
Auckland Clinical Services
Auckland, New Zealand
Christchurch Clinical Studies Trust Ltd.
Christchurch, New Zealand
Sponsors and Collaborators
Alios Biopharma Inc.
Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Alios Biopharma Inc.
ClinicalTrials.gov Identifier: NCT01554085     History of Changes
Other Study ID Numbers: ALS-2158-201
Study First Received: March 12, 2012
Last Updated: September 26, 2012
Health Authority: New Zealand: Medsafe

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on September 18, 2014