Prediabetic StatePhase 2NCT02330549

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

A Phase 2 study testing Cenicriviroc 150 mg in people with Prediabetic State and Non-alcoholic Fatty Liver Disease, run by Tobira Therapeutics, Inc. at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Prediabetic State, Non-alcoholic Fatty Liver Disease, Type 2 Diabetes Mellitus
What is being tested?: Cenicriviroc 150 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 45 participants
Where: 3 sitesin 2 countries
Study dates: 17 Jul 2015to 8 Sep 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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

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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
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.

Trial locations and contacts

3 sites in 2 countries.

Country

City, postcode or hospital

3 sites in 2 countries

United States2 sites

San Antonio Military Medical Center
Fort Sam Houston, Texas, 78234
Gastroenterology Consultants of San Antonio Digestive Research Center
San Antonio, Texas, 78258

Other trials in United States

Puerto Rico1 site

Fundacion de Investigacion
San Juan, 00927-4807

Other trials in Puerto Rico

About this study

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)

Read the detailed 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.

Conditions: Prediabetic State, Non-alcoholic Fatty Liver Disease, Type 2 Diabetes Mellitus
Being tested: Cenicriviroc 150 mg, Placebo
Medical subject headings: Prediabetic State, Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Cenicriviroc 150 mgDrug
Cenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food.
PlaceboDrug
Placebo-matching CVC administered orally once daily and taken every morning with food.

Study groups in NCT02330549
Study group	Role	What they receive
Cenicriviroc 150 mg	Experimental	Cenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food for up to 24 weeks. Receives: 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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Baseline (Day 1) to Weeks 12 and 24

Secondary outcomes (53)

Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue
Macrophage infiltration in adipose tissue was assessed in paraffin-embedded adipose punch biopsies by immunohistochemistry stained for cluster of differentiation 68 (CD68), cluster of differentiation 163 (CD163), C-C chemokine receptor type 2 (CCR2), C-C chemokine receptor type 5 (CCR5) and cluster of differentiation 206 (CD206). A reduction in infiltration indicates less inflammation. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: 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
CCR2 and CCR5 corresponding ligands' messenger ribonucleic acid (mRNA) gene expression were assessed in frozen adipose tissue by quantitative polymerase chain reaction (PCR). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16)
Peripheral monocyte subsets (cluster of differentiation 14 (CD14/cluster of differentiation 16 (CD16)] were measured in fresh peripheral blood mononuclear cells (PBMCs) samples by flow cytometry. Monocyte results are reported for Total, Classical (CD14+CD16-), Intermediate (CD14+CD16+) and Non-classical (CD14lowCD16+). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Fasting Plasma Glucose (FPG)
A fasting blood sample was collected and was sent to a central laboratory for analysis of glucose. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day1) to Weeks 12 and 24
Change From Baseline in Fasting Plasma Insulin (FPI)
A fasting blood sample was collected and was sent to a central laboratory for analysis of insulin. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI)
QUICKI is used to measure insulin sensitivity. QUICKI = 1/(log FPI μIU/mL + log FPG mg/dL). A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.
Measured: Baseline (Day1) to Weeks 12 and 24
Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR)
HOMA-IR = (FPG mg/dL x FPI μIU/mL)/405. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B)
HOMA-%B= (20 × FPI)/(FPG - 3.5). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c)
A fasting blood sample was collected and was sent to a central laboratory for analysis of glucose. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Plasma Glucagon Concentration
A fasting blood sample was collected and was sent to a central laboratory for analysis of glucagon. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 12 and 24
Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load
Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of glucose.
Measured: Prior to Glucose Load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load
Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of insulin.
Measured: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose
AUC(0-120 min) was derived from the serum glucose values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose
AUC(30-120 min) was derived from the serum glucose values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (0-120 Min) for Plasma Insulin
AUC(0-120 min) was derived from the plasma insulin values obtained during the oral glucose tolerance test. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.
Measured: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (30-120 Min) for Plasma Insulin
AUC(30-120 min) was derived from the plasma insulin values obtained during the oral glucose tolerance test. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.
Measured: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in Fasting Free Fatty Acids
A fasting blood sample was collected and was sent to a central laboratory for analysis of free fatty acids. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Serum Adiponectin Concentration
A fasting blood sample was collected and was sent to a central laboratory for analysis of adiponectin. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.
Measured: Baseline (Day1) to Weeks 12 and 24
Change From Baseline in Serum Resistin Concentration
A fasting blood sample was collected and was sent to a central laboratory for analysis of resistin. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 12 and 24
Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load
Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of FFA.
Measured: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (0-120 Min) for Serum FFA
AUC(0-120 min) was derived from the serum FFA values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (30-120 Min) for Serum FFA
AUC(30-120 min) was derived from the serum FFA values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
Liver biopsy were performed during Screening and at Week 24 only for participants diagnosed with NASH. NAFLD activity score was determined based on 3 components: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x) and hepatocellular ballooning (0=none to 2= many cells/prominent ballooning) for a total possible score of 0 to 8. A negative change from Baseline indicates improvement.
Measured: Baseline (Screening) to Week 24
Number of Participants by NASH Clinical Research Network (CRN) Staging Categories
Liver biopsy were performed during Screening and at Week 24 for participants diagnosed with NASH. The NASH CRN Brunt/Kleiner Fibrosis Staging System Fibrosis Stages are: 0 (None), 1 (Perisinusoidal or periportal), 1A (Mild, zone 3, perisinusoidal), 1B (Moderate, zone 3, perisinusoidal), 1C (Portal/periportal), 2 (Perisinusoidal and portal/periportal), 3 (Bridging fibrosis) and 4 (Cirrhosis).
Measured: Baseline (Screening) and Week 24
Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1)
Blood was collected and was sent to a central laboratory for analysis of MCP-1. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES
Blood was collected and was sent to a central laboratory for analysis of RANTES (regulated on activation normal T-cell expressed and secreted). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α)
Blood was collected and was sent to a central laboratory for analysis of MIP-1α. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β)
Blood was collected and was sent to a central laboratory for analysis of MIP-1β. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β)
Blood was collected and was sent to a central laboratory for analysis of IL-1β. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6)
Blood was collected and was sent to a central laboratory for analysis of IL-6. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8)
Blood was collected and was sent to a central laboratory for analysis of IL-8. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10)
Blood was collected and was sent to a central laboratory for analysis of IL-1β. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP)
Blood was collected and was sent to a central laboratory for analysis of hs-CRP. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12, 24
Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α)
Blood was collected and was sent to a central laboratory for analysis of TNF-α. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Weeks 2, 12, 24
Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid
Blood was collected and was sent to a central laboratory for analysis of Hyaluronic Acid. A positive change from Baseline indicates improvement and a negative change from Baseline indicates improvement.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65]
Blood was collected and was sent to a central laboratory for analysis of CK-18. A positive change from Baseline indicates improvement and a negative change from Baseline indicates improvement.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21)
Blood was collected and was sent to a central laboratory for analysis of FGF-21. A negative change from Baseline indicates improvement and a positive change from Baseline indicates improvement.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP)
Blood was collected and was sent to a central laboratory for analysis of Mac-2BP. A negative change from Baseline indicates improvement and a positive change from Baseline indicates improvement.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95)
Blood was collected and was sent to a central laboratory for analysis of CD95. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP)
Blood was collected and was sent to a central laboratory for analysis of AFP. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline (Day 1) to Week 24
Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction
LiverMultiscan™ tests via MRI were obtained at Baseline and at Weeks 12 and 24. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline to Weeks 12 and 24
Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1)
LiverMultiscan™ via MRI were obtained at Baseline and at Weeks 12 and 24. The mean of 4 regions of interest as selected by the technician is reported. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline to Weeks 12 and 24
Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver
LiverMultiscan™ via MRI were obtained at Baseline and at Weeks 12 and 24. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline to Weeks 12 and 24
Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score
LiverMultiscan™ tests via MRI were obtained at Baseline and at Weeks 12 and 24. The mean of 4 regions of interest as selected by the technician is reported. The LIF Score ranges from 0=no liver disease to 4=severe liver disease. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline to Weeks 12 and 24
Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content
LiverMultiscan™ tests via MRI were obtained at Baseline and at Weeks 12 and 24. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.
Measured: Baseline to Weeks 12 and 24
Change From Baseline in Body Weight
A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT)
Blood was collected and was sent to a central laboratory for analysis of ALT. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline to Weeks 12 and 24
Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST)
Blood was collected and was sent to a central laboratory for analysis of AST. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Measured: Baseline to Weeks 12 and 24
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs or worsens after receiving study drug.
Measured: 24 weeks
Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
Vital signs included Systolic Blood Pressure, Diastolic Blood Pressure, Heart Rate, Respiratory Rate and Temperature. The investigator determined if the vital sign measurements were clinically relevant.
Measured: 24 weeks
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results
A standard 12 lead ECG was performed. The investigator determined if the abnormal results were clinically significant.
Measured: Baseline 24 weeks
Plasma Cenicriviroc Concentrations
Measured: Baseline (Day 1) one sample predose; Weeks 2, 12 and 24 one sample predose and one sample postdose
Number of Participants With Abnormal Physical Examination Findings
Physical examination included assessment of the following body systems: Abdomen, Cardiovascular, Extremities, Head, Eyes, Ears, Nose, Throat, Lungs, Lymph Nodes, Neurological, Skin and Thyroid. The number of participants with any abnormal findings at Baseline and participants with any abnormal findings Post-Baseline are reported.
Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Jul 20158 Sep 2016

First posted5 Jan 2015 (estimated)
Study start17 Jul 2015
Primary completion11 Aug 2016
Study completion8 Sep 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Prediabetic StateStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02330549
Sponsor's protocol ID: 652-2-204
Status last verified: Sep 2019
First submitted: 22 Dec 2014
Last updated: 11 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT02330549
Acronym / sponsor ID: 652-2-204
Conditions: Prediabetic State, Non-alcoholic Fatty Liver Disease, Type 2 Diabetes Mellitus
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: Tobira Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 17 Jul 2015 (actual)
Primary completion: 11 Aug 2016 (actual)
Study completion: 8 Sep 2016 (actual)
First posted: 5 Jan 2015 (estimated)
Results: Posted 11 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed 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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Cenicriviroc 150 mg	Experimental	Drug: Cenicriviroc 150 mgCenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food for up to 24 weeks.
Placebo	Placebo comparator	Drug: PlaceboPlacebo-matching CVC, administered orally once daily and taken every morning with food for up to 24 weeks.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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%

Key exclusion criteria (20 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cenicriviroc 150 mgCenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food.	Drug	Cenicriviroc 150 mg
PlaceboPlacebo-matching CVC administered orally once daily and taken every morning with food.	Drug	Placebo

Primary outcome

Change From Baseline in Matsuda Index
Time frame: Baseline (Day 1) to Weeks 12 and 24
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.
Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index
Time frame: Baseline (Day 1) to Weeks 12 and 24
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.

53 secondary outcomes

Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue
Time frame: 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
Time frame: Baseline (Day 1) to Week 24
Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16)
Time frame: Baseline (Day 1) to Week 24
Change From Baseline in Fasting Plasma Glucose (FPG)
Time frame: Baseline (Day1) to Weeks 12 and 24
Change From Baseline in Fasting Plasma Insulin (FPI)
Time frame: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI)
Time frame: Baseline (Day1) to Weeks 12 and 24
Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR)
Time frame: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B)
Time frame: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c)
Time frame: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Plasma Glucagon Concentration
Time frame: Baseline (Day 1) to Weeks 12 and 24
Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load
Time frame: Prior to Glucose Load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load
Time frame: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (0-120 Min) for Plasma Insulin
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (30-120 Min) for Plasma Insulin
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in Fasting Free Fatty Acids
Time frame: Baseline (Day 1) to Weeks 12 and 24
Change From Baseline in Serum Adiponectin Concentration
Time frame: Baseline (Day1) to Weeks 12 and 24
Change From Baseline in Serum Resistin Concentration
Time frame: Baseline (Day 1) to Weeks 12 and 24
Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load
Time frame: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (0-120 Min) for Serum FFA
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in AUC (30-120 Min) for Serum FFA
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
Time frame: Baseline (Screening) to Week 24
Number of Participants by NASH Clinical Research Network (CRN) Staging Categories
Time frame: Baseline (Screening) and Week 24
Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1)
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α)
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β)
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β)
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6)
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8)
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10)
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP)
Time frame: Baseline (Day 1) to Weeks 2, 12, 24
Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α)
Time frame: Baseline (Day 1) to Weeks 2, 12, 24
Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid
Time frame: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65]
Time frame: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21)
Time frame: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP)
Time frame: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95)
Time frame: Baseline (Day 1) to Week 24
Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP)
Time frame: Baseline (Day 1) to Week 24

Results and safety

Results posted to the registry on 11 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cenicriviroc 150 mg	20	16
Placebo	25	24

Primary outcome: Change From Baseline in Matsuda Index

Time frame: Baseline (Day 1) to Weeks 12 and 24. Mean (Standard Deviation). Unit: unit on a scale

Measure	Cenicriviroc 150 mg n = 20	Placebo n = 25
Baseline	1.22 (0.661)	1.04 (0.595)
Change from Baseline to Week 12	-0.02 (0.348)	0.24 (0.656)
Change from Baseline to Week 24	0.03 (0.449)	0.41 (0.674)

Cenicriviroc 150 mg vs Placebo: LS Mean Difference: -0.2286 (95% CI -0.62 to 0.17), p = 0.2483, ANCOVA
Cenicriviroc 150 mg vs Placebo: LS Mean Difference: -0.4113 (95% CI -0.83 to 0.01), p = 0.053, ANCOVA

Population analysed: Intent to treat (ITT) population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. Number analyzed is the number of participants with data available for analysis at the given timepoint.

Primary outcome: Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index

Time frame: Baseline (Day 1) to Weeks 12 and 24. Mean (Standard Deviation). Unit: unit on a scale

Measure	Cenicriviroc 150 mg n = 20	Placebo n = 25
Baseline	17.77 (14.074)	17.74 (9.406)
Change from Baseline to Week 12	-1.41 (9.009)	-0.52 (8.745)
Change from Baseline to Week 24	-0.29 (7.524)	-4.22 (11.612)

Cenicriviroc 150 mg vs Placebo: LS Mean Difference: -1.505 (95% CI -6.33 to 3.32), p = 0.5297, ANCOVA
Cenicriviroc 150 mg vs Placebo: LS Mean Difference: 3.2146 (95% CI -2.4 to 8.83), p = 0.2522, ANCOVA

Population analysed: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. Number analyzed is the number of participants with data available for analysis at the given timepoint.

53 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose of study drug to within 28 days post last dose of study drug (Up to approximately 29 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cenicriviroc 150 mg	0 of 20 (0%)	10 of 20 (50%)	0 of 20
Placebo	1 of 25 (4%)	11 of 25 (44%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Eric Lefebvre, MD study director

Allergan

3 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cenicriviroc 150 mg in people with Prediabetic State and Non-alcoholic Fatty Liver Disease, run by Tobira Therapeutics, Inc. at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Matsuda Index (time frame: Baseline (Day 1) to Weeks 12 and 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02330549.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2019.