Clinical trial NCT01554085: First in Human Study of ALS-002158; Single Dose, Food Effect in Healthy Volunteers; Multiple Doses in Chronic Hepatitis C Genotype 1
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatitis C, Chronic
Lead sponsor: Alios Biopharma Inc.
Sponsor class: INDUSTRY
Collaborators: name: Vertex Pharmaceuticals Incorporated
First posted: 2012-03-14
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Tabulation of adverse events, physical exam, vital signs, 12-lead ECGs, and clinical lab results
timeFrame: Part 1: Day 1-8; Part 2: Day 1-16; Part 3: Day 1-31
Secondary outcomes:
measure: Pharmacokinetic parameters and urinary excretion of ALS-002158 and metabolites
timeFrame: Part 1: Day 1-8; Part 2: Day 1-16; Part 3: Day 1-31
measure: HCV ribonucleic acid (RNA) viral load reduction
timeFrame: Baseline to Day 31
measure: Sequence analysis of the Hepatitis C virus (HCV) NS5B region
timeFrame: Baseline up to Month 6
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: QPharm
state: Queensland
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
city: Perth
country: Australia
facility: Linear Clinical Research Ltd
state: Western Australia
city: Auckland
country: New Zealand
facility: Auckland Clinical Services
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust Ltd.
Study officials:
References: