Clinical trial NCT02760758: A Study of CDI-31244: A Novel NNI in HV and HCV Infected Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Keywords: non-nucleoside inhibitor
NNI
HCV
DAA
Lead sponsor: Cocrystal Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2016-05-04
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of treatment emergent adverse events (AE)
timeFrame: Day 1 to Day 35
Secondary outcomes:
measure: Measure plasma levels of CDI-31244 after SD
timeFrame: Day 1 to Day 6
measure: Measure plasma levels of CDI-31244 after SD in fasted and fed conditions
timeFrame: Day 1 to Day 13
measure: Measure plasma levels of CDI-31244 after MD
timeFrame: Day 1 to Day 13
measure: Measure HCV viral load through the RNA quantitative test
timeFrame: Day 1 to Day 35
measure: Measure HCV mutation through genotyping at baseline and after CDI-31244 dosing
timeFrame: Day 1 to 35
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Algorithme
state: Quebec
Study officials:
affiliation: Cocrystal Pharma, Inc.
name: Judy Pattassery
role: STUDY_DIRECTOR
References: