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

Phase 1

Completed

• Conditions: Hepatitis C
• Interventions: Drug: CDI-31244; Drug: Placebo

• Registration Number: NCT02760758
• Lead Sponsor: Cocrystal Pharma, Inc.

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.

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-04-27
• Study First Submitted QC: 2016-05-01
• Study First Posted: 2016-05-04
• Status Verified: 2016-08
• Primary Completion: 2017-03
• Study Completion: 2017-04
• Last Update Submitted: 2021-04-19
• Last Update Posted: 2021-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (1)

Algorithme; 🇨🇦 Montreal, Quebec, Canada