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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase Ia/Ib Study Assessing Single and Multiple Doses of CDI-31244: A Non-Nucleoside Inhibitor in Healthy and Hepatitis C Virus-Infected Subjects

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: CDI-31244
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1A HV<br>CDI-31244 20 mg active or placebo single dose (SD) | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 2A HV<br>CDI-31244 50 mg active or placebo SD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 3A HV<br>CDI-31244 100 mg active or placebo SD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 4A HV<br>CDI-31244 200 mg active or placebo SD; food effect | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 5A HV<br>CDI-31244 400 mg active or placebo SD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 6A HV<br>CDI-31244 200 mg active or placebo multiple dose (MD) | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 7A HV<br>CDI-31244 200 mg active or placebo MD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 8A HV<br>CDI-31244 400 mg active or placebo MD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 1B HCV genotype (GT) 1<br>CDI-31244 400 mg active or placebo MD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 2B HCV GT 1<br>CDI-31244 600 mg active or placebo MD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|
| Experimental: Cohort 3B HCV GT 1<br>CDI-31244 800 mg active or placebo MD | Drug: CDI-31244<br>* NNI<br>* Other names: CC-31244;Drug: Placebo<br>* no active ingredients<br>* Other names: CDI-31244 Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment emergent adverse events (AE) | 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 | Day 1 to Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure plasma levels of CDI-31244 after SD | Plasma levels of CDI-31244 in the the single dose HV cohorts | Day 1 to Day 6 | 
| Measure plasma levels of CDI-31244 after SD in fasted and fed conditions | The effect of food on the plasma levels of CDI-31244 in the single dose HV cohorts | Day 1 to Day 13 | 
| Measure plasma levels of CDI-31244 after MD | Plasma levels of CDI-31244 in the multiple dose HV and HCV infected cohorts | Day 1 to Day 13 | 
| Measure HCV viral load through the RNA quantitative test | 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 | Day 1 to Day 35 | 
| Measure HCV mutation through genotyping at baseline and after CDI-31244 dosing | The possible emergence of hepatitis C virus resistance mutation in HCV infected subjects | Day 1 to 35 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-nucleoside inhibitor, NNI, HCV, DAA