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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02760758
• Other study ID #: CDI-31244-P1-001
• Status: Completed
• Phase: Phase 1
• Start date: April 2016
• Est. completion date: April 2017

Study information

• Verified date: August 2016
• Source: Cocrystal Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: April 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C

Intervention

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

Locations

Country	Name	City	State
Canada	Algorithme	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Cocrystal Pharma, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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