A Study of CDI-31244: A Novel NNI in HV and HCV Infected Subjects

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.

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.