First in Human Study of ALS-002200; 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-002200 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-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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: ALS-002200

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Biotrial
  • Brittany
    • Rennes, Brittany, France
      • Biotrial
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • ARENSIA
• Romania
  • Bucharest, Romania
    • ARENSIA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: ALS-002200	Drug: ALS-002200; ALS-002200

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	data points measured include patient reported adverse events, physical exams, vital signs, 12-lead ECGs and clinical lab results	up to Day 31

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Comparison of baseline with on-treatment or post-treatment Hepatitis C virus (HCV) NS5B RNA sequence	Baseline up to Month 6

Collaborators and Investigators

• Sponsor: Alios Biopharma Inc.
• Collaborators: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2011
• Primary Completion (Actual): February 28, 2013
• Study Completion (Actual): February 28, 2013

Study Registration Dates

• First Submitted: March 12, 2012
• First Submitted That Met QC Criteria: May 2, 2012
• First Posted (Estimate): May 3, 2012

Study Record Updates

• Last Update Posted (Actual): October 31, 2017
• Last Update Submitted That Met QC Criteria: October 27, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: ALS-2200-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No