ORION: Effects of Cenicriviroc on Insulin Sensitivity in Subjects With Prediabetes or Type 2 Diabetes Mellitus (T2DM) and Suspected NAFLD

NCT02330549 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 652-2-204
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

Prediabetic State; Non-alcoholic Fatty Liver Disease; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Matsuda Index

  Change in peripheral insulin sensitivity was measured by the Matsuda Index. Fasting plasma glucose (FPG) and fasting plasma insulin (FPI) concentrations measured during the oral glucose tolerance test (OGTT) were used to calculate the Matsuda Index. Matsuda Index=10,000/square root \[FPG mg/dL x FPI μIU/mL) x (mean glucose mg/dL x mean insulin μIU/mL during OGTT)\]. A Matsuda index of \<2.5 indicates whole body insulin resistance. A lower Matsuda Index indicates the worst disease state. An increase in the Matsuda Index indicates an improvement in insulin sensitivity (best). A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

  Baseline (Day 1) to Weeks 12 and 24

• Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index

  Change in adipose insulin sensitivity was measured by Adipo-IR. Adipo-IR= (Fasting Serum free fatty acid (FFA) mmol/L x FPI μIU/mL). A higher Adipo-IR index indicates the worst disease state. A lower Adipo-IR Index is best. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

  Baseline (Day 1) to Weeks 12 and 24

Secondary Outcomes (53)

• Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue

  Baseline (Day 1) to Week 24

• Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue

  Baseline (Day 1) to Week 24

• Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16)

  Baseline (Day 1) to Week 24

• Change From Baseline in Fasting Plasma Glucose (FPG)

  Baseline (Day1) to Weeks 12 and 24

• Change From Baseline in Fasting Plasma Insulin (FPI)

  Baseline (Day 1) to Weeks 12 and 24

Study Arms (2)

Cenicriviroc 150 mg

EXPERIMENTAL

Cenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food for up to 24 weeks.

Drug: Cenicriviroc 150 mg

Placebo

PLACEBO COMPARATOR

Placebo-matching CVC, administered orally once daily and taken every morning with food for up to 24 weeks.

Drug: Placebo

Interventions

Cenicriviroc 150 mg DRUG

Cenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food.

Cenicriviroc 150 mg

Placebo DRUG

Placebo-matching CVC administered orally once daily and taken every morning with food.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%
• Participants 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
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 upper limit normal (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
• Participants receiving allowed concomitant medications need to be on stable therapy for 28 days prior to Baseline.

You may not qualify if:

• Use of oral antihyperglycemic agents (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
• Hepatitis B Surface Antigen (HBsAg) positive
• Human Immunodeficiency Virus-1 (HIV-1) or Human Immunodeficiency Virsu-2 (HIV-2) infection
• Hepatitis C Virus Antibody (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 participant 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

Sponsors & Collaborators

• Tobira Therapeutics, Inc.: lead

Study Sites (3)

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Gastroenterology Consultants of San Antonio Digestive Research Center

San Antonio, Texas, 78258, United States

Location

Fundacion de Investigacion

San Juan, 00927-4807, Puerto Rico

Location

MeSH Terms

Conditions

Prediabetic State; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Interventions

cenicriviroc

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Eric Lefebvre, MD

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: January 5, 2015
• Study Start: July 17, 2015
• Primary Completion: August 11, 2016
• Study Completion: September 8, 2016
• Last Updated: October 11, 2019
• Results First Posted: October 11, 2019

Record last verified: 2019-09

Locations

US (2); PR (1)