This is a Phase 1, randomized, double-blind, placebo-controlled, first-in-human, 3-part study in which the safety, tolerability, and pharmacokinetics of orally administered AL-704 will be assessed in healthy adult subjects and in adult subjects with CHC infection. Part 1: Healthy adult subjects will receive one of 5 single ascending oral doses (SAD) of AL-704 ranging from 100 mg to 1,500 mg (Cohorts 1 to 5). Within each cohort subjects will be randomized to receive either AL-704 or placebo (n=8 per cohort; 6 assigned to AL-704 and 2 assigned to placebo), in a fasted state. The planned dose-escalation scheme may be changed based on the emerging PK and safety data. Two additional cohorts (Cohorts 6 and 7) may be enrolled for evaluation of additional doses at the discretion of the Sponsor and Investigator, based on the emerging pharmacokinetic (PK) profile, and the presence of an acceptable safety profile. Part 2: To assess the food effect on pharmacokinetics, 8 healthy subjects from one full Part 1 cohort who received a single dose of AL-704 or placebo in a fasted state, will receive the same single dose of AL-704 or placebo in a fed state in Part 2 after a washout period of 7-14 days (depending on PK results). It is expected that Cohort 3 of Part 1 (600 mg dose) will be selected, however this depends on the evaluation of available PK and safety data from Part 1 of the study. Part 3: The following cohorts of 10 adult subjects each, with CHC infection, will be evaluated. Subjects with CHC genotype 1 infection (Cohorts 8 to 10) and subjects with CHC genotype 3 infection (Cohort 11) will be randomized to receive AL-704 or placebo for 7 consecutive days (n=10 per cohort, 8 assigned to AL-704 and 2 assigned to placebo) in a fed state. The treatment is anticipated to be administered in a once daily dose regimen or a twice daily dose regimen. The dose and dose regimen to be administered will be determined by the Sponsor depending on the PK and safety outcomes of previous cohorts.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
42
Biotrial
Rennes, Brittany Region, France
Arensia
Tbilisi, Georgia
Arensia
Chisinau, Moldova
Safety Data assessed by Number and frequency of treatment emergent adverse events, physical examination findings
abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results examination findings, vital signs, ECG and clinical lab results
Time frame: From screening to last visit (up to 21 days)
Single dose PK Profile from Cmax, tmax, t1/2, CL/F and Vz/F, AUC0-inf or AUClast
Time frame: From dosing to Day 8 visit for each SAD/FE cohort
Multiple dose PK: profile from Cmax, tmax, t1/2, AUClast and AUC0 tau
Time frame: From dosing to final study visit (21 days) for each cohort
Hepatitis C virus levels
HCV RNA viral load change from baseline to final study visit in subjects with Chronic hepatitis C infection
Time frame: From screening to final study visit (21 days) for each cohort
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