Overview

This trial is active, not recruiting.

Conditions prediabetic state, non-alcoholic fatty liver disease, type 2 diabetes mellitus
Treatments cenicriviroc 150 mg, matching placebo
Phase phase 2
Sponsor Tobira Therapeutics, Inc.
Start date June 2015
End date September 2016
Trial size 45 participants
Trial identifier NCT02330549, 652-2-204

Summary

A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study of CVC to be conducted in approximately 50 adult obese subjects (BMI ≥ 30 kg/m2) with prediabetes or type 2 diabetes mellitus and suspected NALFD.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
CVC 150 mg, administered orally once daily and taken every morning with food for 24 weeks
cenicriviroc 150 mg CVC 150 mg
CVC 150 mg, administered orally once daily and taken every morning with food
(Placebo Comparator)
Matching placebo, administered orally once daily and taken every morning with food for 24 weeks
matching placebo
Matching placebo administered orally once daily and taken every morning with food

Primary Outcomes

Measure
Changes in Insulin Sensitivity Measured by Peripheral and Adipose Tissue
time frame: 24 weeks

Secondary Outcomes

Measure
Degree of Macrophage Infiltration in Subcutaneous Adipose Tissue
time frame: 24 weeks
Expression of Chemokine Receptors Types 2 (CCR2) and 5 (CCR5) in Subcutaneous Adipose Tissue
time frame: 24 weeks
Changes from Baseline in Peripheral Monocyte Subsets (CD14/CD16)
time frame: 24 weeks
Changes in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™)
time frame: 24 weeks
Correlation of Non-invasive Liver Imaging Findings with Histology Results
time frame: 24 weeks
Changes from Baseline in Liver Transaminases
time frame: 24 weeks
Changes from Baseline in Serum Biomarker Panel
time frame: 24 weeks
Changes from Baseline in Metabolic Parameters
time frame: 24 weeks
Number and Percentage of Subjects with Adverse Events over 24 Weeks
time frame: 24 weeks
Changes from Baseline in Physical Examination over 24 Weeks
time frame: 24 weeks
Changes from Baseline in Vital Signs over 24 Weeks
time frame: 24 weeks
Changes from Baseline in 12 Lead ECG over 24 weeks
time frame: 24 weeks
Pharmacokinetics (PK) of CVC in a population PK analysis
time frame: 24 weeks

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: - Adult male and female subjects aged between 18-75 years - Obesity as defined by BMI ≥ 30 kg/m2 - Evidence of prediabetes or type 2 diabetes mellitus based on Screening laboratory values with at least one of the following criteria: - Fasting plasma glucose (FPG) of 100 - 270 mg/dL (5.6 - 15.0 mmol/L) - Hemoglobin A1c (HbA1c) of 5.7 - 10.0% - Subjects receiving metformin alone or in combination with a sulfonylurea (glimepiride, glipizide, glyburide, or gliclazide) must be on stable therapy for at least 90 days prior to Screening. - Suspected diagnosis of NAFLD warranting confirmation by liver biopsy - AST and ALT ≤ 5 ULN - Ability to understand and sign a written informed consent form - Females of child-bearing potential and males participating in the study must agree to use at least 2 approved barrier methods of contraception throughout the duration of the study and for 3 months after stopping study drug. Females who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and serum follicle stimulating hormone (FSH) ≥ 30 mU/mL - Subjects receiving allowed concomitant medications need to be on stable therapy for 28 days prior to Baseline Exclusion Criteria: - Use of OHAs other than metformin or sulfonylureas, including but not limited to thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, meglitinides, α-glucosidase inhibitors, colesevelam, bromocriptine, pramlintide or basal insulin within 90 days prior to Screening or anticipated use during the trial - Type 1 diabetes - HBsAg positive - HIV-1 or HIV-2 infection - HCVAb positive - Prior or planned liver transplantation - Other known causes of chronic liver disease, including alcoholic liver disease - History of cirrhosis and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding - Alcohol consumption greater than 14 units/week - Weight reduction through bariatric surgery or planned bariatric surgery during the conduct of the study (including gastric banding) - Any Grade ≥ 3 laboratory abnormality as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Toxicity Grading Scale, except subjects with Grade ≥ 3 dyslipidemia with triglyceride or cholesterol elevations unless clinical assessment foresees an immediate health risk to the subject - Serum albumin < 3.5 g/dL - Serum creatinine levels ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females if subject is receiving metformin - Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) equation - Platelet count < 100,000/mm3 - Hemoglobin < 12 g/dL for males or < 11 g/dL for females - Females who are pregnant or breastfeeding - Receiving ongoing therapy with any disallowed medication at Screening - Allergy to the study drug or its components - Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements

Additional Information

Official title ORION - Effect of CCR2 and CCR5 Antagonism by Cenicriviroc on Peripheral and Adipose Tissue Insulin Sensitivity in Adult Obese Subjects With Prediabetes or Type 2 Diabetes Mellitus and Suspected Non-Alcoholic Fatty Liver Disease (NAFLD)
Description Approximately 50 adult obese subjects (BMI ≥ 30 kg/m2) with prediabetes or type 2 diabetes mellitus and suspected NALFD will be randomized into the study. Eligible subjects will receive either CVC (n=25) or matching placebo (n=25), once daily (QD) for 24 weeks, followed by a safety follow-up visit 4 weeks after last intake of study medication.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Tobira Therapeutics, Inc..