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

Sponsor

Cocrystal Pharma, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02760758

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

6.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: CDI-31244 Drug: Placebo	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

76 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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 Start Date :

Apr 1, 2016

Actual Primary Completion Date :

Mar 1, 2017

Actual Study Completion Date :

Apr 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.