Hepatitis C
Conditions
Keywords
non-nucleoside inhibitor, NNI, HCV, DAA
Brief summary
This is a First in Human study of orally administered CDI-31244, a non-nucleoside inhibitor (NNI) in healthy volunteers and HCV infected individuals
Detailed description
This is a single center, double-blind, placebo-controlled, randomized, single ascending oral dose and multiple oral dose design, incorporating fed/fasted comparisons. The study will include two groups: Group A - single ascending dose (SAD) including a food effect cohort, and multiple dose (MD) in healthy volunteers (HV), and Group B MD in Hepatitis C Virus (HCV) infected individuals divided in two parts. Five single-dose cohort are planned. For the five single-dose cohorts, a sentinel group of 2 subjects will be dosed at least one day prior to enrolling remaining subjects. Six multiple-dose cohorts are planned. Three multiple dose cohorts in healthy volunteers and three cohorts in HCV-infected individuals. The dosing of Group B will be conducted following safety and pharmacokinetic (PK) review of Group A. The dosing of Group B, Part 2 will be conducted only if Part 1 shows acceptable safety and efficacy results.
Interventions
DRUGCDI-31244
NNI
DRUGPlacebo
no active ingredients
Sponsors
Cocrystal Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: HV and HCV INFECTED SUBJECTS: * Male or female aged ≥ 18 to ≤ 65 years; * Body mass index ≥ 18.5 to ≤ 35.0 kg/m2; * Body weight ≥ 50 kg; * Negative screening for alcohol and drugs of abuse; * Normal results on 12-lead electrocardiogram (ECG); * For females, negative result on a pregnancy test. HCV INFECTED SUBJECTS: * HCV treatment-naïve subjects must have not received prior direct acting agent (DAA) treatment for hepatitis C infection; * Documented clinical history compatible with chronic hepatitis C; * HCV Genotype 1 by HCV genotyping performed at Screening; * Plasma HCV RNA ≥ 5.0 log10 IU/mL at Screening; * Laboratory evidence of no cirrhosis (negative liver biopsy or fibroscan or FibroTest, F2 or lower) within one year prior to study), if these are not available, do a FibroTest at screening, which must be F2 or lower. Main
Exclusion criteria
HV and HCV INFECTED SUBJECTS: * Females who are pregnant or are lactating; * Co-infected with hepatitis B virus (HBV, HBsAg positive) and/or human immunodeficiency virus (HIV); * Abuse of alcohol and/or drugs that could interfere with adherence to study requirements as judged by the investigator; * Positive screen result for drugs of abuse or alcohol on Day -1. Use of other investigational drugs within 60 days of dosing; * Subject with intestinal malabsorption; * Presence of out-of-range cardiac interval on the screening ECG or other clinically significant ECG abnormalities; * Serum creatinine \> upper limit of normal (ULN); * Any clinically significant medical condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results. HEALTHY VOLUNTEERS: * Positive screen for anti-HCV antibody HCV INFECTED SUBJECTS: * Clinical (in the opinion of the investigator) or laboratory evidence of cirrhosis; * History or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency; * History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC; * Active clinically significant diseases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment emergent adverse events (AE) | Day 1 to Day 35 | The safety and the tolerability of single and multiple oral doses of CDI-31244 through number of AEs observed in HV and HCV infected subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure plasma levels of CDI-31244 after SD | Day 1 to Day 6 | Plasma levels of CDI-31244 in the the single dose HV cohorts |
| Measure plasma levels of CDI-31244 after SD in fasted and fed conditions | Day 1 to Day 13 | The effect of food on the plasma levels of CDI-31244 in the single dose HV cohorts |
| Measure plasma levels of CDI-31244 after MD | Day 1 to Day 13 | Plasma levels of CDI-31244 in the multiple dose HV and HCV infected cohorts |
| Measure HCV viral load through the RNA quantitative test | Day 1 to Day 35 | The clinical efficacy of CDI-31244 in HCV-infected subjects as measured by the maximal change in antiviral activity through changes in the HCV RNA load |
| Measure HCV mutation through genotyping at baseline and after CDI-31244 dosing | Day 1 to 35 | The possible emergence of hepatitis C virus resistance mutation in HCV infected subjects |
Countries
Canada
Outcome results
None listed