Clinical Trials/NCT03253471

NCT03253471

Terminated

Phase 1

A Randomized, Double-blind, Placebo-controlled, First-in-human, 3 Part Study of Orally Administered AL-611 to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (Part 3) of Single Ascending Doses in Healthy Volunteers (Parts 1-2), and Multiple Ascending Doses in Subjects With Chronic Hepatitis C Virus Infection (Part 3)

Alios Biopharma Inc.1 site in 1 country24 target enrollmentJuly 7, 2017

ConditionsHepatitis C

InterventionsAL-611 Placebo

DrugsAL-611 Placebo

Overview

Phase: Phase 1
Intervention: AL-611
Conditions: Hepatitis C
Sponsor: Alios Biopharma Inc.
Enrollment: 24
Locations: 1
Primary Endpoint: Incidence and severity of Treatment emergent Adverse events
Status: Terminated
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This randomized, double-blind, placebo-controlled, 3-part study will assess the safety, tolerability, pharmacokinetics (PK), and antiviral activity (Part 3 only) of orally administered AL-611 in healthy volunteers (HV; Parts 1-2) and subjects with CHC (Part 3).

Part 1: HV will receive 1 of 5 single ascending doses (SAD) of AL-611 Part 2: Eight HV from Cohort 3 in Part 1 are planned to receive a second single dose of AL-611 or placebo (as per their randomized assignment in Part 1) in a fed state after a washout period Part 3: Subjects with CHC infection will receive 1 of 3 planned multiple ascending doses (MAD)

Registry

clinicaltrials.gov

Start Date

July 7, 2017

End Date

September 18, 2017

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alios Biopharma Inc.

Responsible Party

Sponsor

Eligibility Criteria

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.
•Except in compensated cirrhosis (cirrhosis cohorts only) and diagnosis of HCV (Part 3 only), subject is in good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests, and ECG.
•Male or female, 18-60 years of age for HV and 18-70 years of age for subjects with CHC.
•Body mass index (BMI) 18-30 kg/m2, inclusive, for HV and 18-35 kg/m\^2, inclusive, for subjects with CHC. The minimum weight is 50 kg in both populations.
•A female subject is eligible to participate in this study if she is of non-childbearing potential (defined as females with a documented tubal ligation, bilateral oophorectomy, or hysterectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females).
•If male, subject is surgically sterile or practicing specific forms of birth control until 6 months after the end of the study. Male subjects must agree to refrain from sperm donation from start of dosing through 6 months after the completion of study drug administration.
•Subject agrees to refrain from blood donation from screening until 56 days after the last study visit.
•For HV, estimated glomerular filtration rate (eGFR) in the normal range as determined by modification of diet in renal disease (MDRD) formula. For CHC (Part 3) eGFR\>60ml/min/1.73m\^2 as determined by MDRD (alternative calculations (eg, Cockroft-Gault) may be permissible, if approved by the Sponsor).
•Additional inclusion criteria for subjects with CHC infection (Part 3):

Exclusion Criteria

•History or other clinical evidence of significant or unstable cardiac disease (eg, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia (eg, long QT syndrome, torsades de pointes), coronary heart disease), moderate to severe valvular disease or poorly controlled hypertension at screening.
•Family history of prolonged QT syndrome (eg, torsade de pointes) or sudden cardiac death.
•Clinically significant abnormal screening ECG findings (eg, PR \>220 msec, QRS interval \>120 msec or corrected QT interval (QTcF) \>450 msec for male subjects and \>470 msec for female subjects).
•Participation in either an investigational drug trial or an investigational vaccine trial within 30 days or 5 half lives (whichever is longer) prior to starting study medication.
•Clinically significant blood loss or elective blood donation of significant volume (ie, \>500 mL) within 60 days prior to screening; \>1 unit of plasma within 7 days prior to screening.
•Unwilling to abstain from alcohol for 48 hours prior to the start of dosing through the study completion visit.
•History of regular alcohol intake \>14 units per week of alcohol for females and \>21 units per week for males (one unit is defined as 10 g alcohol) within 3 months of randomization
•The subject has a positive alcohol test at screening or on Day -
•Hypersensitivity to the active substance or to any of the excipients of AL-611
•Abnormal (using local normal range) heart rate, respiratory rate, temperature or blood pressure (BP) values (evaluated in a semi-recumbent or recumbent position after 5 minutes of rest). One repeat measurement after an additional \~5 minutes of rest is permitted. In addition, a repeat measurement performed on a separate day is also permitted.

Arms & Interventions

AL-611

Intervention: AL-611

Placebo to Match AL-611

Intervention: Placebo

Outcomes

Primary Outcomes

Incidence and severity of Treatment emergent Adverse events

Time Frame: Up to 21 days

Incidence and severity of vital sign abnormalities

Time Frame: Up to 21 days

Incidence and severity of clinical laboratory abnormalities

Time Frame: Up to 21 days

Physical examination findings

Time Frame: Up to 21 days

Incidence and severity of 12 lead electrocardiagram abnormalities

Time Frame: Up to 21 days

Secondary Outcomes

Vz/F of AL-611 following single dose administration(Day 1 to Day 8)
Cmax of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
Concentrations in urine of AL-611 and ALS 022358 (and other metabolites if applicable) after a single oral dose(Day 1 to Day 8)
HCV RNA viral load in subjects with CHC(Screening to Day 21)
Clast of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
t1/2 of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
CL/F of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
C0_h of AL-611 and ALS-022358 (and other metabolites if applicable) following repeat dose administration(Day 1 to Day 21)
Sequence analysis of HCV(Day 1 to Day 21)
AUClast of AL-611 and ALS-022358 (and other metabolites if applicable) following repeat dose administration(Day 1 to Day 21)
C24h of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
AUC0-inf of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
AUClast of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
Cmax of AL-611 and ALS-022358 (and other metabolites if applicable) following repeat dose administration(Day 1 to Day 21)
tmax of AL-611 and ALS-022358 (and other metabolites if applicable) following repeat dose administration(Day 1 to Day 21)
Cmin of AL-611 and ALS-022358 (and other metabolites if applicable) following repeat dose administration(Day 1 to Day 21)
t1/2 of AL-611 and ALS-022358 (and other metabolites if applicable) following repeat dose administration(Day 1 to Day 21)
tmax of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
tlast of AL-611 and ALS-022358 (and other metabolites if applicable) following single dose administration(Day 1 to Day 8)
AUC0_tau of AL-611 and ALS-022358 (and other metabolites if applicable) following repeat dose administration(Day 1 to Day 21)