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

Overview

This is a First in Human study of orally administered CDI-31244, a non-nucleoside inhibitor (NNI) in healthy volunteers and HCV infected individuals

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: March 2017

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

  • Drug: CDI-31244
    • NNI
  • Drug: Placebo
    • no active ingredients

Arms, Groups and Cohorts

  • Experimental: Cohort 1A HV
    • CDI-31244 20 mg active or placebo single dose (SD)
  • Experimental: Cohort 2A HV
    • CDI-31244 50 mg active or placebo SD
  • Experimental: Cohort 3A HV
    • CDI-31244 100 mg active or placebo SD
  • Experimental: Cohort 4A HV
    • CDI-31244 200 mg active or placebo SD; food effect
  • Experimental: Cohort 5A HV
    • CDI-31244 400 mg active or placebo SD
  • Experimental: Cohort 6A HV
    • CDI-31244 200 mg active or placebo multiple dose (MD)
  • Experimental: Cohort 7A HV
    • CDI-31244 200 mg active or placebo MD
  • Experimental: Cohort 8A HV
    • CDI-31244 400 mg active or placebo MD
  • Experimental: Cohort 1B HCV genotype (GT) 1
    • CDI-31244 400 mg active or placebo MD
  • Experimental: Cohort 2B HCV GT 1
    • CDI-31244 600 mg active or placebo MD
  • Experimental: Cohort 3B HCV GT 1
    • CDI-31244 800 mg active or placebo MD

Clinical Trial Outcome Measures

Primary Measures

  • Number of treatment emergent adverse events (AE)
    • Time Frame: 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 Measures

  • Measure plasma levels of CDI-31244 after SD
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Day 1 to 35
    • The possible emergence of hepatitis C virus resistance mutation in HCV infected subjects

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Cocrystal Pharma, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Judy Pattassery, Study Director, Cocrystal Pharma, Inc.

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