Non-alcoholic Fatty Liver Disease, Prediabetic State, Type 2 Diabetes Mellitus
Conditions
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.
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.
Interventions
Cenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food.
DRUGPlacebo
Placebo-matching CVC administered orally once daily and taken every morning with food.
Sponsors
Tobira Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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% * 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.
Exclusion criteria
* 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 * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Matsuda Index | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Baseline (Day 1) to Week 24 | 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. |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline (Day1) to Weeks 12 and 24 | 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. |
| Change From Baseline in Fasting Plasma Insulin (FPI) | Baseline (Day 1) to Weeks 12 and 24 | 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. |
| Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline (Day1) to Weeks 12 and 24 | 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. |
| Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR) | Baseline (Day 1) to Weeks 12 and 24 | 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. |
| Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B) | Baseline (Day 1) to Weeks 12 and 24 | HOMA-%B= (20 × FPI)/(FPG - 3.5). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening. |
| Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c) | Baseline (Day 1) to Weeks 12 and 24 | 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. |
| Change From Baseline in Plasma Glucagon Concentration | Baseline (Day 1) to Weeks 12 and 24 | 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. |
| Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Prior to Glucose Load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of glucose. |
| Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of insulin. |
| Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose | Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | 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. |
| Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose | Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | 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. |
| Change From Baseline in AUC (0-120 Min) for Plasma Insulin | Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | 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. |
| Change From Baseline in AUC (30-120 Min) for Plasma Insulin | Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | 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. |
| Change From Baseline in Fasting Free Fatty Acids | Baseline (Day 1) to Weeks 12 and 24 | 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. |
| Change From Baseline in Serum Adiponectin Concentration | Baseline (Day1) to Weeks 12 and 24 | 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. |
| Change From Baseline in Serum Resistin Concentration | Baseline (Day 1) to Weeks 12 and 24 | 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. |
| Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of FFA. |
| Change From Baseline in AUC (0-120 Min) for Serum FFA | Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | 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. |
| Change From Baseline in AUC (30-120 Min) for Serum FFA | Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24 | 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. |
| Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | Baseline (Screening) to Week 24 | 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. |
| Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline (Screening) and Week 24 | 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). |
| Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Baseline (Day 1) to Weeks 2, 12 and 24 | 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. |
| Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Baseline (Day 1) to Weeks 2, 12, 24 | 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. |
| Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Baseline (Day 1) to Weeks 2, 12, 24 | 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. |
| Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid | Baseline (Day 1) to Week 24 | 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. |
| Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65] | Baseline (Day 1) to Week 24 | 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. |
| Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21) | Baseline (Day 1) to Week 24 | 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. |
| Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP) | Baseline (Day 1) to Week 24 | 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. |
| Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95) | Baseline (Day 1) to Week 24 | 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. |
| Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP) | Baseline (Day 1) to Week 24 | 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. |
| Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction | Baseline to Weeks 12 and 24 | 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. |
| Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1) | Baseline to Weeks 12 and 24 | 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. |
| Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver | Baseline to Weeks 12 and 24 | 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. |
| Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score | Baseline to Weeks 12 and 24 | 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. |
| Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content | Baseline to Weeks 12 and 24 | 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. |
| Change From Baseline in Body Weight | Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24 | A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening. |
| Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT) | Baseline to Weeks 12 and 24 | 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. |
| Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST) | Baseline to Weeks 12 and 24 | 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. |
| Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | Baseline (Day 1) to Week 24 | 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. |
| Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs | 24 weeks | 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. |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results | Baseline 24 weeks | A standard 12 lead ECG was performed. The investigator determined if the abnormal results were clinically significant. |
| Plasma Cenicriviroc Concentrations | 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 | 24 weeks | 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. |
| Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | 24 weeks | 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. |
| 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 | 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. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cenicriviroc 150 mg Cenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food for up to 24 weeks. | 20 |
| Placebo Placebo-matching CVC, administered orally once daily and taken every morning with food for up to 24 weeks. | 25 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Failure to meet randomization criteria | 1 | 0 |
| Overall Study | Subject withdrew consent | 2 | 1 |
Baseline characteristics
| Characteristic | Cenicriviroc 150 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 9.67 | 51.0 years STANDARD_DEVIATION 8.98 | 52.2 years STANDARD_DEVIATION 9.27 |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 25 |
| other Total, other adverse events | 10 / 20 | 11 / 25 |
| serious Total, serious adverse events | 0 / 20 | 1 / 25 |
Outcome results
Primary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index | Change from Baseline to Week 12 | -1.41 unit on a scale | Standard Deviation 9.009 |
| Cenicriviroc 150 mg | Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index | Baseline | 17.77 unit on a scale | Standard Deviation 14.074 |
| Cenicriviroc 150 mg | Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index | Change from Baseline to Week 24 | -0.29 unit on a scale | Standard Deviation 7.524 |
| Placebo | Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index | Baseline | 17.74 unit on a scale | Standard Deviation 9.406 |
| Placebo | Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index | Change from Baseline to Week 12 | -0.52 unit on a scale | Standard Deviation 8.745 |
| Placebo | Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index | Change from Baseline to Week 24 | -4.22 unit on a scale | Standard Deviation 11.612 |
Comparison: Change from Baseline to Week 12p-value: 0.529795% CI: [-6.33, 3.32]ANCOVA
Comparison: Change from Baseline to Week 24p-value: 0.252295% CI: [-2.4, 8.83]ANCOVA
Primary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Matsuda Index | Baseline | 1.22 unit on a scale | Standard Deviation 0.661 |
| Cenicriviroc 150 mg | Change From Baseline in Matsuda Index | Change from Baseline to Week 12 | -0.02 unit on a scale | Standard Deviation 0.348 |
| Cenicriviroc 150 mg | Change From Baseline in Matsuda Index | Change from Baseline to Week 24 | 0.03 unit on a scale | Standard Deviation 0.449 |
| Placebo | Change From Baseline in Matsuda Index | Baseline | 1.04 unit on a scale | Standard Deviation 0.595 |
| Placebo | Change From Baseline in Matsuda Index | Change from Baseline to Week 12 | 0.24 unit on a scale | Standard Deviation 0.656 |
| Placebo | Change From Baseline in Matsuda Index | Change from Baseline to Week 24 | 0.41 unit on a scale | Standard Deviation 0.674 |
Comparison: Change from Baseline to Week 12p-value: 0.248395% CI: [-0.62, 0.17]ANCOVA
Comparison: Change form Baseline to Week 24p-value: 0.05395% CI: [-0.83, 0.01]ANCOVA
Secondary
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.
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose | Baseline | 22601 minutes (min)*mg/dL | Standard Deviation 6423 |
| Cenicriviroc 150 mg | Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose | Change from Baseline to Week 24 | 329 minutes (min)*mg/dL | Standard Deviation 4883 |
| Cenicriviroc 150 mg | Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose | Change from Baseline to Week 12 | -1071 minutes (min)*mg/dL | Standard Deviation 4098 |
| Placebo | Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose | Change from Baseline to Week 12 | -1031 minutes (min)*mg/dL | Standard Deviation 3322 |
| Placebo | Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose | Baseline | 24977 minutes (min)*mg/dL | Standard Deviation 5543 |
| Placebo | Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose | Change from Baseline to Week 24 | -1085 minutes (min)*mg/dL | Standard Deviation 4178 |
Secondary
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.
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose | Baseline | 17816 minutes (min)*mg/dL | Standard Deviation 5488 |
| Cenicriviroc 150 mg | Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose | Change from Baseline to Week 12 | -941 minutes (min)*mg/dL | Standard Deviation 3490 |
| Cenicriviroc 150 mg | Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose | Change from Baseline to Week 24 | 383 minutes (min)*mg/dL | Standard Deviation 4380 |
| Placebo | Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose | Baseline | 20097 minutes (min)*mg/dL | Standard Deviation 4620 |
| Placebo | Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose | Change from Baseline to Week 12 | -923 minutes (min)*mg/dL | Standard Deviation 3092 |
| Placebo | Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose | Change from Baseline to Week 24 | -889 minutes (min)*mg/dL | Standard Deviation 3497 |
Secondary
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.
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in AUC (0-120 Min) for Plasma Insulin | Baseline | 21261 min*μIU/mL | Standard Deviation 10716 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (0-120 Min) for Plasma Insulin | Change from Baseline to Week 12 | 640 min*μIU/mL | Standard Deviation 6340 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (0-120 Min) for Plasma Insulin | Change from Baseline to Week 24 | 2101 min*μIU/mL | Standard Deviation 8088 |
| Placebo | Change From Baseline in AUC (0-120 Min) for Plasma Insulin | Baseline | 24411 min*μIU/mL | Standard Deviation 13942 |
| Placebo | Change From Baseline in AUC (0-120 Min) for Plasma Insulin | Change from Baseline to Week 12 | -1850 min*μIU/mL | Standard Deviation 6916 |
| Placebo | Change From Baseline in AUC (0-120 Min) for Plasma Insulin | Change from Baseline to Week 24 | -1703 min*μIU/mL | Standard Deviation 9109 |
Secondary
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.
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in AUC (0-120 Min) for Serum FFA | Baseline | 37.2 min*mmol/L | Standard Deviation 14.27 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (0-120 Min) for Serum FFA | Change from Baseline to Week 12 | -5.4 min*mmol/L | Standard Deviation 10.16 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (0-120 Min) for Serum FFA | Change from Baseline to Week 24 | -3.4 min*mmol/L | Standard Deviation 11.74 |
| Placebo | Change From Baseline in AUC (0-120 Min) for Serum FFA | Baseline | 42.9 min*mmol/L | Standard Deviation 14.57 |
| Placebo | Change From Baseline in AUC (0-120 Min) for Serum FFA | Change from Baseline to Week 12 | -1.3 min*mmol/L | Standard Deviation 14.46 |
| Placebo | Change From Baseline in AUC (0-120 Min) for Serum FFA | Change from Baseline to Week 24 | -4.2 min*mmol/L | Standard Deviation 18.98 |
Secondary
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.
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in AUC (30-120 Min) for Plasma Insulin | Baseline | 18178 min*μIU/mL | Standard Deviation 9082 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (30-120 Min) for Plasma Insulin | Change from Baseline to Week 12 | 472 min*μIU/mL | Standard Deviation 5730 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (30-120 Min) for Plasma Insulin | Change from Baseline to Week 24 | 1818 min*μIU/mL | Standard Deviation 7506 |
| Placebo | Change From Baseline in AUC (30-120 Min) for Plasma Insulin | Baseline | 21583 min*μIU/mL | Standard Deviation 12626 |
| Placebo | Change From Baseline in AUC (30-120 Min) for Plasma Insulin | Change from Baseline to Week 12 | -1830 min*μIU/mL | Standard Deviation 6532 |
| Placebo | Change From Baseline in AUC (30-120 Min) for Plasma Insulin | Change from Baseline to Week 24 | -1467 min*μIU/mL | Standard Deviation 8523 |
Secondary
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.
Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in AUC (30-120 Min) for Serum FFA | Baseline | 23.3 min*mmol/L | Standard Deviation 11.55 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (30-120 Min) for Serum FFA | Change from Baseline to Week 12 | -5.0 min*mmol/L | Standard Deviation 7.49 |
| Cenicriviroc 150 mg | Change From Baseline in AUC (30-120 Min) for Serum FFA | Change from Baseline to Week 24 | -4.2 min*mmol/L | Standard Deviation 8.61 |
| Placebo | Change From Baseline in AUC (30-120 Min) for Serum FFA | Baseline | 25.6 min*mmol/L | Standard Deviation 8.59 |
| Placebo | Change From Baseline in AUC (30-120 Min) for Serum FFA | Change from Baseline to Week 12 | -0.9 min*mmol/L | Standard Deviation 8.65 |
| Placebo | Change From Baseline in AUC (30-120 Min) for Serum FFA | Change from Baseline to Week 24 | -1.5 min*mmol/L | Standard Deviation 11.08 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12, 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Baseline | 6.39 mg/L | Standard Deviation 9.232 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Change from Baseline to Week 2 | -1.58 mg/L | Standard Deviation 4.642 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Change from Baseline to Week 12 | -0.50 mg/L | Standard Deviation 8.402 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Change from Baseline to Week 24 | -1.35 mg/L | Standard Deviation 2.843 |
| Placebo | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Change from Baseline to Week 24 | 0.14 mg/L | Standard Deviation 5.615 |
| Placebo | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Baseline | 5.39 mg/L | Standard Deviation 7.421 |
| Placebo | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Change from Baseline to Week 12 | 2.33 mg/L | Standard Deviation 6.813 |
| Placebo | Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP) | Change from Baseline to Week 2 | 0.12 mg/L | Standard Deviation 2.934 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Change from Baseline to Week 2 | 0.20 pg/mL | Standard Deviation 0.772 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Baseline | 3.05 pg/mL | Standard Deviation 0.908 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Change from Baseline to Week 12 | 0.07 pg/mL | Standard Deviation 0.896 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Change from Baseline to Week 24 | -0.61 pg/mL | Standard Deviation 0.406 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Change from Baseline to Week 24 | -0.37 pg/mL | Standard Deviation 0.897 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Change from Baseline to Week 12 | -0.17 pg/mL | Standard Deviation 0.979 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Baseline | 3.06 pg/mL | Standard Deviation 0.694 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10) | Change from Baseline to Week 2 | 0.10 pg/mL | Standard Deviation 0.861 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Baseline | 0.08 pg/mL | Standard Deviation 0.058 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Change from Baseline to Week 2 | -0.03 pg/mL | Standard Deviation 0.082 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Change from Baseline to Week 12 | -0.01 pg/mL | Standard Deviation 0.1 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Change from Baseline to Week 24 | -0.03 pg/mL | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Change from Baseline to Week 24 | -0.14 pg/mL | Standard Deviation 0.42 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Baseline | 0.20 pg/mL | Standard Deviation 0.413 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Change from Baseline to Week 12 | -0.17 pg/mL | Standard Deviation 0.418 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β) | Change from Baseline to Week 2 | -0.16 pg/mL | Standard Deviation 0.413 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Baseline | 3.54 pg/mL | Standard Deviation 3.208 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Change from Baseline to Week 2 | -0.67 pg/mL | Standard Deviation 2.885 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Change from Baseline to Week 12 | -0.88 pg/mL | Standard Deviation 3.299 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Change from Baseline to Week 24 | -1.18 pg/mL | Standard Deviation 2.958 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Change from Baseline to Week 24 | 1.08 pg/mL | Standard Deviation 6.017 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Baseline | 3.68 pg/mL | Standard Deviation 2.274 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Change from Baseline to Week 12 | 0.20 pg/mL | Standard Deviation 3.018 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6) | Change from Baseline to Week 2 | -0.11 pg/mL | Standard Deviation 2.091 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Baseline | 21.99 pg/mL | Standard Deviation 8.454 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Change from Baseline to Week 2 | 0.55 pg/mL | Standard Deviation 7.982 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Change from Baseline to Week 12 | 4.16 pg/mL | Standard Deviation 9.739 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Change from Baseline to Week 24 | 1.31 pg/mL | Standard Deviation 6.228 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Change from Baseline to Week 24 | -0.45 pg/mL | Standard Deviation 6.452 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Baseline | 18.42 pg/mL | Standard Deviation 5.669 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Change from Baseline to Week 12 | 0.44 pg/mL | Standard Deviation 7.475 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8) | Change from Baseline to Week 2 | 3.29 pg/mL | Standard Deviation 7.846 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12, 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Baseline | 12.78 pg/mL | Standard Deviation 3.208 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Change from Baseline to Week 12 | 0.58 pg/mL | Standard Deviation 2.894 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Change from Baseline to Week 2 | 0.68 pg/mL | Standard Deviation 2.577 |
| Cenicriviroc 150 mg | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Change from Baseline to Week 24 | -0.06 pg/mL | Standard Deviation 2.32 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Change from Baseline to Week 24 | -0.97 pg/mL | Standard Deviation 2.361 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Baseline | 12.35 pg/mL | Standard Deviation 2.526 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Change from Baseline to Week 2 | -0.43 pg/mL | Standard Deviation 2.592 |
| Placebo | Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α) | Change from Baseline to Week 12 | -0.69 pg/mL | Standard Deviation 2.484 |
Secondary
Change From Baseline in Body Weight
A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.
Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
Population: Safety Population included all participants who received at least one dose of study drug. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Baseline | 94.92 kg | Standard Deviation 14.282 |
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Change from Baseline to Week 12 | 0.53 kg | Standard Deviation 2.967 |
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Change from Baseline to Week 4 | -0.52 kg | Standard Deviation 2.417 |
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Change from Baseline to Week 16 | 0.87 kg | Standard Deviation 3.16 |
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Change from Baseline to Week 2 | -0.22 kg | Standard Deviation 1.76 |
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Change from Baseline to Week 20 | 0.17 kg | Standard Deviation 3.555 |
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Change from Baseline to Week 8 | 0.21 kg | Standard Deviation 2.029 |
| Cenicriviroc 150 mg | Change From Baseline in Body Weight | Change from Baseline to Week 24 | 0.03 kg | Standard Deviation 3.656 |
| Placebo | Change From Baseline in Body Weight | Change from Baseline to Week 8 | -1.56 kg | Standard Deviation 3.162 |
| Placebo | Change From Baseline in Body Weight | Baseline | 100.92 kg | Standard Deviation 15.359 |
| Placebo | Change From Baseline in Body Weight | Change from Baseline to Week 2 | -1.10 kg | Standard Deviation 2.008 |
| Placebo | Change From Baseline in Body Weight | Change from Baseline to Week 4 | -1.43 kg | Standard Deviation 2.453 |
| Placebo | Change From Baseline in Body Weight | Change from Baseline to Week 24 | -2.44 kg | Standard Deviation 4.417 |
| Placebo | Change From Baseline in Body Weight | Change from Baseline to Week 12 | -1.50 kg | Standard Deviation 3.879 |
| Placebo | Change From Baseline in Body Weight | Change from Baseline to Week 16 | -1.73 kg | Standard Deviation 4.018 |
| Placebo | Change From Baseline in Body Weight | Change from Baseline to Week 20 | -2.15 kg | Standard Deviation 4.152 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available at the given timepoint
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR2, Baseline | 13.0 copies per sample |
| Cenicriviroc 150 mg | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR2, Change from Baseline to Week 24 | 2.6 copies per sample |
| Cenicriviroc 150 mg | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR5, Baseline | 12.7 copies per sample |
| Cenicriviroc 150 mg | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR5, Change from Baseline to Week 24 | 3.6 copies per sample |
| Placebo | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR5, Change from Baseline to Week 24 | 0.1 copies per sample |
| Placebo | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR2, Baseline | 13.7 copies per sample |
| Placebo | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR5, Baseline | 15.2 copies per sample |
| Placebo | Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue | CCR2, Change from Baseline to Week 24 | 0.8 copies per sample |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Fasting Free Fatty Acids | Baseline | 15.36 mg/dL | Standard Deviation 5.708 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Free Fatty Acids | Change from Baseline to Week 12 | -0.74 mg/dL | Standard Deviation 5.214 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Free Fatty Acids | Change from Baseline to Week 24 | -0.09 mg/dL | Standard Deviation 6.466 |
| Placebo | Change From Baseline in Fasting Free Fatty Acids | Baseline | 17.41 mg/dL | Standard Deviation 6.913 |
| Placebo | Change From Baseline in Fasting Free Fatty Acids | Change from Baseline to Week 12 | 0.31 mg/dL | Standard Deviation 7.489 |
| Placebo | Change From Baseline in Fasting Free Fatty Acids | Change from Baseline to Week 24 | -2.65 mg/dL | Standard Deviation 8.856 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c) | Baseline | 6.09 percentage of HbA1c | Standard Deviation 0.735 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c) | Change from Baseline to Week 12 | -0.12 percentage of HbA1c | Standard Deviation 0.634 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c) | Change from Baseline to Week 24 | -0.11 percentage of HbA1c | Standard Deviation 0.567 |
| Placebo | Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c) | Baseline | 6.23 percentage of HbA1c | Standard Deviation 0.778 |
| Placebo | Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c) | Change from Baseline to Week 12 | 0.09 percentage of HbA1c | Standard Deviation 0.379 |
| Placebo | Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c) | Change from Baseline to Week 24 | 0.00 percentage of HbA1c | Standard Deviation 0.503 |
Secondary
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.
Time frame: Baseline (Day1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline | 119.55 mg/dL | Standard Deviation 28.849 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Change from Baseline to Week 12 | -5.56 mg/dL | Standard Deviation 24.328 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Change from Baseline to Week 24 | -3.25 mg/dL | Standard Deviation 19.206 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline | 122.84 mg/dL | Standard Deviation 33.212 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) | Change from Baseline to Week 12 | -3.96 mg/dL | Standard Deviation 24.412 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) | Change from Baseline to Week 24 | -7.83 mg/dL | Standard Deviation 25.61 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Fasting Plasma Insulin (FPI) | Baseline | 33.42 μIU/mL | Standard Deviation 26.427 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Plasma Insulin (FPI) | Change from Baseline to Week 12 | -1.56 μIU/mL | Standard Deviation 10.204 |
| Cenicriviroc 150 mg | Change From Baseline in Fasting Plasma Insulin (FPI) | Change from Baseline to Week 24 | -0.27 μIU/mL | Standard Deviation 8.464 |
| Placebo | Change From Baseline in Fasting Plasma Insulin (FPI) | Baseline | 33.38 μIU/mL | Standard Deviation 24.135 |
| Placebo | Change From Baseline in Fasting Plasma Insulin (FPI) | Change from Baseline to Week 12 | -5.26 μIU/mL | Standard Deviation 19.412 |
| Placebo | Change From Baseline in Fasting Plasma Insulin (FPI) | Change from Baseline to Week 24 | -6.83 μIU/mL | Standard Deviation 18.312 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B) | Baseline | 5.63 unit on a scale | Standard Deviation 3.577 |
| Cenicriviroc 150 mg | Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B) | Change from Baseline to Week 12 | -0.02 unit on a scale | Standard Deviation 1.795 |
| Cenicriviroc 150 mg | Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B) | Change from Baseline to Week 24 | -0.15 unit on a scale | Standard Deviation 1.304 |
| Placebo | Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B) | Baseline | 5.77 unit on a scale | Standard Deviation 4.079 |
| Placebo | Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B) | Change from Baseline to Week 12 | -0.74 unit on a scale | Standard Deviation 2.649 |
| Placebo | Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B) | Change from Baseline to Week 24 | -0.73 unit on a scale | Standard Deviation 3.036 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR) | Baseline | 10.56 unit on a scale | Standard Deviation 10.407 |
| Cenicriviroc 150 mg | Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR) | Change from Baseline to Week 12 | -0.49 unit on a scale | Standard Deviation 3.182 |
| Cenicriviroc 150 mg | Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR) | Change from Baseline to Week 24 | -0.11 unit on a scale | Standard Deviation 3.17 |
| Placebo | Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR) | Baseline | 10.29 unit on a scale | Standard Deviation 8.931 |
| Placebo | Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR) | Change from Baseline to Week 12 | -1.96 unit on a scale | Standard Deviation 8.513 |
| Placebo | Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR) | Change from Baseline to Week 24 | -3.07 unit on a scale | Standard Deviation 7.222 |
Secondary
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.
Time frame: Baseline to Weeks 12 and 24
Population: Safety Population included all participants who received at least one dose of study drug. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT) | Baseline | 55.76 U/L | Standard Deviation 42.044 |
| Cenicriviroc 150 mg | Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT) | Change from Baseline to Week 12 | -0.22 U/L | Standard Deviation 14.621 |
| Cenicriviroc 150 mg | Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT) | Change from Baseline to Week 24 | 0.40 U/L | Standard Deviation 21.223 |
| Placebo | Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT) | Baseline | 51.28 U/L | Standard Deviation 39.066 |
| Placebo | Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT) | Change from Baseline to Week 12 | -6.88 U/L | Standard Deviation 19.856 |
| Placebo | Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT) | Change from Baseline to Week 24 | -8.95 U/L | Standard Deviation 24.3 |
Secondary
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.
Time frame: Baseline to Weeks 12 and 24
Population: Safety Population included all participants who received at least one dose of study drug. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST) | Baseline | 33.88 U/L | Standard Deviation 17.885 |
| Cenicriviroc 150 mg | Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST) | Change from Baseline to Week 12 | 0.46 U/L | Standard Deviation 9.447 |
| Cenicriviroc 150 mg | Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST) | Change from Baseline to Week 24 | 1.57 U/L | Standard Deviation 13.022 |
| Placebo | Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST) | Baseline | 36.10 U/L | Standard Deviation 26.712 |
| Placebo | Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST) | Change from Baseline to Week 12 | -3.31 U/L | Standard Deviation 16.374 |
| Placebo | Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST) | Change from Baseline to Week 24 | -3.75 U/L | Standard Deviation 15.966 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR2+, Baseline | 10.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD68+, Change from BL to Week 24 | 1.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR2+, Change from BL to Week 24 | 0.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD68+, Baseline | 4.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR5+, Baseline | 3.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD163+, Baseline | 9.5 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR5+, Change from BL to Week 24 | 1.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD163+, Change from BL at Week 24 | 2.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD206+, Baseline | 6.0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD206+, Change from BL to Week 24 | 0.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD206+, Baseline | 7.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD206+, Change from BL to Week 24 | -0.5 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD68+, Baseline | 3.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD68+, Change from BL to Week 24 | 1.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD163+, Change from BL at Week 24 | 1.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR2+, Baseline | 10.5 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR2+, Change from BL to Week 24 | 2.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR5+, Baseline | 3.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CCR5+, Change from BL to Week 24 | 0.0 cells/μL |
| Placebo | Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue | CD163+, Baseline | 10.5 cells/μL |
Secondary
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.
Time frame: Baseline to Weeks 12 and 24
Population: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. LiverMultiScan™ tests were performed in a subset of participants at one site. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1) | Baseline | 923.72 milliseconds (ms) | Standard Deviation 76.249 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1) | Change from Baseline to Week 12 | -10.62 milliseconds (ms) | Standard Deviation 22.211 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1) | Change from Baseline to Week 24 | 0.03 milliseconds (ms) | Standard Deviation 28.771 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1) | Baseline | 911.97 milliseconds (ms) | Standard Deviation 88.007 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1) | Change from Baseline to Week 12 | -5.60 milliseconds (ms) | Standard Deviation 52.203 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1) | Change from Baseline to Week 24 | -3.95 milliseconds (ms) | Standard Deviation 55.402 |
Secondary
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.
Time frame: Baseline to Weeks 12 and 24
Population: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. LiverMultiScan™ tests were performed in a subset of participants at one site. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver | Baseline | 917.95 ms | Standard Deviation 68.147 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver | Change from Baseline to Week 12 | -15.37 ms | Standard Deviation 18.348 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver | Change from Baseline to Week 24 | -2.83 ms | Standard Deviation 18.707 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver | Baseline | 901.67 ms | Standard Deviation 77.461 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver | Change from Baseline to Week 12 | -4.00 ms | Standard Deviation 42.298 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver | Change from Baseline to Week 24 | 0.89 ms | Standard Deviation 42.722 |
Secondary
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.
Time frame: Baseline to Weeks 12 and 24
Population: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. LiverMultiScan™ tests were performed in a subset of participants at one site. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction | Baseline | 15.21 percentage of fat | Standard Deviation 9.112 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction | Change from Baseline to Week 12 | -0.05 percentage of fat | Standard Deviation 1.822 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction | Change from Baseline to Week 24 | 1.08 percentage of fat | Standard Deviation 3.238 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction | Baseline | 13.56 percentage of fat | Standard Deviation 7.987 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction | Change from Baseline to Week 12 | -2.75 percentage of fat | Standard Deviation 7.121 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction | Change from Baseline to Week 24 | -5.37 percentage of fat | Standard Deviation 7.486 |
Secondary
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.
Time frame: Baseline to Weeks 12 and 24
Population: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. LiverMultiScan™ tests were performed in a subset of participants at one site. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content | Baseline | 1.24 mg/g of liver | Standard Deviation 0.151 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content | Change from Baseline to Week 12 | 0.03 mg/g of liver | Standard Deviation 0.121 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content | Change from Baseline to Week 24 | 0.00 mg/g of liver | Standard Deviation 0.122 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content | Baseline | 1.29 mg/g of liver | Standard Deviation 0.152 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content | Change from Baseline to Week 12 | -0.06 mg/g of liver | Standard Deviation 0.117 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content | Change from Baseline to Week 24 | -0.14 mg/g of liver | Standard Deviation 0.151 |
Secondary
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.
Time frame: Baseline to Weeks 12 and 24
Population: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. LiverMultiScan™ tests were performed in a subset of participants at one site. Number analyzed were the participants with analysis values at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score | Baseline | 2.50 unit on a scale | Standard Deviation 0.853 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score | Change from Baseline to Week 12 | -0.11 unit on a scale | Standard Deviation 0.259 |
| Cenicriviroc 150 mg | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score | Change from Baseline to Week 24 | 0.01 unit on a scale | Standard Deviation 0.345 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score | Baseline | 2.34 unit on a scale | Standard Deviation 0.868 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score | Change from Baseline to Week 12 | -0.01 unit on a scale | Standard Deviation 0.45 |
| Placebo | Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score | Change from Baseline to Week 24 | -0.00 unit on a scale | Standard Deviation 0.505 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65] | Baseline | 399.35 U/L | Standard Deviation 352.261 |
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65] | Change from Baseline to Week 24 | 1.88 U/L | Standard Deviation 235.362 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65] | Baseline | 485.72 U/L | Standard Deviation 547.707 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65] | Change from Baseline to Week 24 | -88.00 U/L | Standard Deviation 338.731 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21) | Baseline | 266.75 pg/mL | Standard Deviation 119.59 |
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21) | Change from Baseline to Week 24 | -3.53 pg/mL | Standard Deviation 156.894 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21) | Baseline | 406.91 pg/mL | Standard Deviation 260.751 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21) | Change from Baseline to Week 24 | 427.38 pg/mL | Standard Deviation 1925.089 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid | Baseline | 24.65 ng/mL | Standard Deviation 18.511 |
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid | Change from Baseline to Week 24 | 12.69 ng/mL | Standard Deviation 19.622 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid | Baseline | 19.78 ng/mL | Standard Deviation 7.74 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid | Change from Baseline to Week 24 | 4.86 ng/mL | Standard Deviation 15.743 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP) | Baseline | 5440.50 ng/mL | Standard Deviation 1829.772 |
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP) | Change from Baseline to Week 24 | 20.94 ng/mL | Standard Deviation 967.192 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP) | Baseline | 7156.96 ng/mL | Standard Deviation 5336.192 |
| Placebo | Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP) | Change from Baseline to Week 24 | -844.77 ng/mL | Standard Deviation 2231.155 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP) | Baseline | 3.10 ng/mL | Standard Deviation 1.483 |
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP) | Change from Baseline to Week 24 | 0.00 ng/mL | Standard Deviation 0.73 |
| Placebo | Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP) | Change from Baseline to Week 24 | -0.14 ng/mL | Standard Deviation 0.727 |
| Placebo | Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP) | Baseline | 2.91 ng/mL | Standard Deviation 1.925 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95) | Baseline | 10.99 ng/mL | Standard Deviation 2.478 |
| Cenicriviroc 150 mg | Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95) | Change from Baseline to Week 24 | -0.34 ng/mL | Standard Deviation 2.259 |
| Placebo | Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95) | Baseline | 11.11 ng/mL | Standard Deviation 1.737 |
| Placebo | Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95) | Change from Baseline to Week 24 | -1.00 ng/mL | Standard Deviation 2.085 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 24
Population: Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Classical Monocytes, Change from BL to Week 24 | -43.6 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Total Monocytes, Change from Baseline to Week 24 | 0 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Intermediate Monocytes, Baseline | 16.8 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Total Monocytes, Baseline (BL) | 400 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Intermediate Monocytes, Change from BL to Week 24 | -1.4 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Classical Monocytes, Baseline | 258 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Non-Classical Monocytes, Baseline | 24.9 cells/μL |
| Cenicriviroc 150 mg | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Non-Classical Monocytes, Change from BL to Week 24 | -7.1 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Non-Classical Monocytes, Change from BL to Week 24 | -2.4 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Total Monocytes, Baseline (BL) | 400 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Total Monocytes, Change from Baseline to Week 24 | 0 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Classical Monocytes, Baseline | 351 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Classical Monocytes, Change from BL to Week 24 | -31 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Intermediate Monocytes, Baseline | 22.4 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Intermediate Monocytes, Change from BL to Week 24 | 3.8 cells/μL |
| Placebo | Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16) | Non-Classical Monocytes, Baseline | 30.9 cells/μL |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Plasma Glucagon Concentration | Baseline | 154.26 ng/mL | Standard Deviation 32.877 |
| Cenicriviroc 150 mg | Change From Baseline in Plasma Glucagon Concentration | Change from Baseline to Week 12 | 20.25 ng/mL | Standard Deviation 23.251 |
| Cenicriviroc 150 mg | Change From Baseline in Plasma Glucagon Concentration | Change from Baseline to Week 24 | 19.07 ng/mL | Standard Deviation 35.977 |
| Placebo | Change From Baseline in Plasma Glucagon Concentration | Baseline | 169.13 ng/mL | Standard Deviation 36.591 |
| Placebo | Change From Baseline in Plasma Glucagon Concentration | Change from Baseline to Week 12 | 4.61 ng/mL | Standard Deviation 36.505 |
| Placebo | Change From Baseline in Plasma Glucagon Concentration | Change from Baseline to Week 24 | 19.14 ng/mL | Standard Deviation 53.373 |
Secondary
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.
Time frame: Baseline (Day1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) | Change from Baseline to Week 12 | 0.00 unit on a scale | Standard Deviation 0.018 |
| Cenicriviroc 150 mg | Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline | 0.29 unit on a scale | Standard Deviation 0.025 |
| Cenicriviroc 150 mg | Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) | Change from Baseline to Week 24 | 0.01 unit on a scale | Standard Deviation 0.019 |
| Placebo | Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline | 0.29 unit on a scale | Standard Deviation 0.023 |
| Placebo | Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) | Change from Baseline to Week 12 | 0.00 unit on a scale | Standard Deviation 0.02 |
| Placebo | Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) | Change from Baseline to Week 24 | 0.01 unit on a scale | Standard Deviation 0.02 |
Secondary
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.
Time frame: Baseline (Day1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Serum Adiponectin Concentration | Baseline | 3.99 μg/mL | Standard Deviation 2.162 |
| Cenicriviroc 150 mg | Change From Baseline in Serum Adiponectin Concentration | Change from Baseline to Week 12 | -0.01 μg/mL | Standard Deviation 0.465 |
| Cenicriviroc 150 mg | Change From Baseline in Serum Adiponectin Concentration | Change from Baseline to Week 24 | 0.64 μg/mL | Standard Deviation 2.693 |
| Placebo | Change From Baseline in Serum Adiponectin Concentration | Baseline | 4.50 μg/mL | Standard Deviation 2.253 |
| Placebo | Change From Baseline in Serum Adiponectin Concentration | Change from Baseline to Week 12 | 0.01 μg/mL | Standard Deviation 0.937 |
| Placebo | Change From Baseline in Serum Adiponectin Concentration | Change from Baseline to Week 24 | -0.82 μg/mL | Standard Deviation 2.222 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Baseline | 445.86 pg/mL | Standard Deviation 140.656 |
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Change from Baseline to Week 2 | 1333.68 pg/mL | Standard Deviation 497.505 |
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Change from Baseline to Week 12 | 1461.98 pg/mL | Standard Deviation 663.465 |
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Change from Baseline to Week 24 | 1248.86 pg/mL | Standard Deviation 661.883 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Change from Baseline to Week 12 | 31.98 pg/mL | Standard Deviation 80.034 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Change from Baseline to Week 24 | 13.87 pg/mL | Standard Deviation 79.726 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Change from Baseline to Week 2 | 37.58 pg/mL | Standard Deviation 71.741 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1) | Baseline | 408.19 pg/mL | Standard Deviation 117.099 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Baseline | 36.95 ng/mL | Standard Deviation 19.267 |
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Change from Baseline to Week 24 | -2.13 ng/mL | Standard Deviation 29.003 |
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Change from Baseline to Week 2 | -1.53 ng/mL | Standard Deviation 20.643 |
| Cenicriviroc 150 mg | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Change from Baseline to Week 12 | -2.53 ng/mL | Standard Deviation 18.729 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Baseline | 46.33 ng/mL | Standard Deviation 28.419 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Change from Baseline to Week 12 | 0.65 ng/mL | Standard Deviation 19.31 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Change from Baseline to Week 2 | -1.13 ng/mL | Standard Deviation 20.726 |
| Placebo | Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES | Change from Baseline to Week 24 | -5.35 ng/mL | Standard Deviation 28.724 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Baseline | 69.66 pg/mL | Standard Deviation 20.275 |
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Change from Baseline to Week 2 | 64.11 pg/mL | Standard Deviation 21.811 |
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Change from Baseline to Week 12 | 63.75 pg/mL | Standard Deviation 21.811 |
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Change from Baseline to Week 24 | 61.08 pg/mL | Standard Deviation 18.224 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Change from Baseline to Week 24 | -2.79 pg/mL | Standard Deviation 9.445 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Baseline | 62.85 pg/mL | Standard Deviation 15.737 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Change from Baseline to Week 12 | -6.28 pg/mL | Standard Deviation 10.135 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α) | Change from Baseline to Week 2 | -0.11 pg/mL | Standard Deviation 8.583 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 2, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Baseline | 120.59 pg/mL | Standard Deviation 40.483 |
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Change from Baseline to Week 2 | 163.26 pg/mL | Standard Deviation 77.537 |
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Change from Baseline to Week 12 | 152.21 pg/mL | Standard Deviation 67.341 |
| Cenicriviroc 150 mg | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Change from Baseline to Week 24 | 147.83 pg/mL | Standard Deviation 58.465 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Change from Baseline to Week 24 | -7.42 pg/mL | Standard Deviation 15.499 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Baseline | 102.85 pg/mL | Standard Deviation 41.424 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Change from Baseline to Week 12 | -3.04 pg/mL | Standard Deviation 20.482 |
| Placebo | Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β) | Change from Baseline to Week 2 | 1.06 pg/mL | Standard Deviation 15.232 |
Secondary
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.
Time frame: Baseline (Day 1) to Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in Serum Resistin Concentration | Change from Baseline to Week 12 | -0.49 ng/mL | Standard Deviation 3.019 |
| Cenicriviroc 150 mg | Change From Baseline in Serum Resistin Concentration | Baseline | 10.46 ng/mL | Standard Deviation 3.724 |
| Cenicriviroc 150 mg | Change From Baseline in Serum Resistin Concentration | Change from Baseline to Week 24 | -0.01 ng/mL | Standard Deviation 4.168 |
| Placebo | Change From Baseline in Serum Resistin Concentration | Baseline | 10.44 ng/mL | Standard Deviation 4.422 |
| Placebo | Change From Baseline in Serum Resistin Concentration | Change from Baseline to Week 12 | 0.10 ng/mL | Standard Deviation 3.316 |
| Placebo | Change From Baseline in Serum Resistin Concentration | Change from Baseline to Week 24 | -1.19 ng/mL | Standard Deviation 2.957 |
Secondary
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.
Time frame: Baseline (Screening) to Week 24
Population: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. Only participants confirmed at Screening with NASH by biopsy and had a biopsy conducted at Week 24 were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | Baseline | 4.33 score on a scale | Standard Deviation 0.816 |
| Cenicriviroc 150 mg | Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | Change from Baseline to Week 24 | -1.00 score on a scale | Standard Deviation 1.265 |
| Placebo | Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | Change from Baseline to Week 24 | -0.33 score on a scale | Standard Deviation 1.67 |
| Placebo | Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | Baseline | 4.00 score on a scale | Standard Deviation 1.279 |
Secondary
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).
Time frame: Baseline (Screening) and Week 24
Population: ITT population included all participants randomized to the treatment group assigned, regardless of starting treatment or changing treatment during the study. Only participants confirmed at Screening with NASH by biopsy and had a biopsy conducted at Week 24 were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 0 | 2 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1 | 2 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1A | 1 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1B | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1C | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 2 | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 3 | 1 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 4 | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 0 | 2 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1 | 3 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1A | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1B | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1C | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 2 | 0 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 3 | 1 Participants |
| Cenicriviroc 150 mg | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24 : Stage 4 | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24 : Stage 4 | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 0 | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 0 | 4 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1 | 7 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1C | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1A | 3 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1 | 6 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1B | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 3 | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 1C | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1A | 2 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 2 | 2 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 2 | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 3 | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Week 24: Stage 1B | 0 Participants |
| Placebo | Number of Participants by NASH Clinical Research Network (CRN) Staging Categories | Baseline: Stage 4 | 0 Participants |
Secondary
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.
Time frame: 24 weeks
Population: Safety Population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cenicriviroc 150 mg | Number of Participants With Abnormal Physical Examination Findings | Baseline | 3 Participants |
| Cenicriviroc 150 mg | Number of Participants With Abnormal Physical Examination Findings | Post-Baseline | 3 Participants |
| Placebo | Number of Participants With Abnormal Physical Examination Findings | Baseline | 8 Participants |
| Placebo | Number of Participants With Abnormal Physical Examination Findings | Post-Baseline | 13 Participants |
Secondary
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.
Time frame: 24 weeks
Population: Safety Population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cenicriviroc 150 mg | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | 10 Participants |
| Placebo | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | 18 Participants |
Secondary
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.
Time frame: 24 weeks
Population: Safety Population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cenicriviroc 150 mg | Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs | 0 Participants |
| Placebo | Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs | 0 Participants |
Secondary
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.
Time frame: Baseline 24 weeks
Population: Safety Population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cenicriviroc 150 mg | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results | 0 Participants |
Secondary
Plasma Cenicriviroc Concentrations
Time frame: Baseline (Day 1) one sample predose; Weeks 2, 12 and 24 one sample predose and one sample postdose
Population: Pharmacokinetic (PK) Population included all participants in the safety population who received at least 1 dose of study drug and had at least 1 PK assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Plasma Cenicriviroc Concentrations | Baseline: Pre-Dose | 0.0 ng/mL | Standard Deviation 0 |
| Cenicriviroc 150 mg | Plasma Cenicriviroc Concentrations | Week 2: Pre-Dose | 168.7 ng/mL | Standard Deviation 165.53 |
| Cenicriviroc 150 mg | Plasma Cenicriviroc Concentrations | Week 2: Post-Dose | 170.7 ng/mL | Standard Deviation 182.87 |
| Cenicriviroc 150 mg | Plasma Cenicriviroc Concentrations | Week 12: Pre-Dose | 383.3 ng/mL | Standard Deviation 755.28 |
| Cenicriviroc 150 mg | Plasma Cenicriviroc Concentrations | Week 12: Post-Dose | 320.4 ng/mL | Standard Deviation 623.34 |
| Cenicriviroc 150 mg | Plasma Cenicriviroc Concentrations | Week 24: Pre-Dose | 230.7 ng/mL | Standard Deviation 382.75 |
| Cenicriviroc 150 mg | Plasma Cenicriviroc Concentrations | Week 24: Post-Dose | 127.4 ng/mL | Standard Deviation 92.26 |
Secondary
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.
Time frame: Prior to Glucose Load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 30 minutes | 193.93 mg/dL | Standard Deviation 32.458 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 120 minutes | 158.38 mg/dL | Standard Deviation 46.411 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: Prior to Glucose Load | 107.88 mg/dL | Standard Deviation 12.638 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: Prior to Glucose Load | 111.47 mg/dL | Standard Deviation 20.035 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 60 minutes | 201.44 mg/dL | Standard Deviation 49.884 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 30 minutes | 198.60 mg/dL | Standard Deviation 44.223 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 90 minutes | 187.20 mg/dL | Standard Deviation 53.835 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 90 minutes | 173.56 mg/dL | Standard Deviation 56.169 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 120 minutes | 165.73 mg/dL | Standard Deviation 53.378 |
| Cenicriviroc 150 mg | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 60 minutes | 214.93 mg/dL | Standard Deviation 58.414 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 120 minutes | 191.26 mg/dL | Standard Deviation 86.539 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 60 minutes | 232.09 mg/dL | Standard Deviation 66.036 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: Prior to Glucose Load | 119.39 mg/dL | Standard Deviation 28.8 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 30 minutes | 205.90 mg/dL | Standard Deviation 50.327 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 60 minutes | 232.74 mg/dL | Standard Deviation 62.174 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 90 minutes | 227.00 mg/dL | Standard Deviation 76.041 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 120 minutes | 201.04 mg/dL | Standard Deviation 82.832 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: Prior to Glucose Load | 114.88 mg/dL | Standard Deviation 39.591 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 30 minutes | 198.65 mg/dL | Standard Deviation 59.787 |
| Placebo | Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 90 minutes | 220.61 mg/dL | Standard Deviation 78.385 |
Secondary
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.
Time frame: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: Prior to Glucose Load | 25.94 μIU/mL | Standard Deviation 12.065 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 60 minutes | 211.76 μIU/mL | Standard Deviation 72.218 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 30 minutes | 168.71 μIU/mL | Standard Deviation 61.276 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: Prior to Glucose Load | 25.25 μIU/mL | Standard Deviation 15.571 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 30 minutes | 172.31 μIU/mL | Standard Deviation 78.152 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 90 minutes | 204.47 μIU/mL | Standard Deviation 108.028 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 60 minutes | 219.63 μIU/mL | Standard Deviation 134.629 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 120 minutes | 216.00 μIU/mL | Standard Deviation 119.872 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 90 minutes | 218.06 μIU/mL | Standard Deviation 105.188 |
| Cenicriviroc 150 mg | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 120 minutes | 218.71 μIU/mL | Standard Deviation 158.013 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 90 minutes | 233.22 μIU/mL | Standard Deviation 175.669 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 60 minutes | 203.29 μIU/mL | Standard Deviation 168.986 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 120 minutes | 223.96 μIU/mL | Standard Deviation 172.155 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: Prior to Glucose Load | 26.54 μIU/mL | Standard Deviation 12.608 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 120 minutes | 265.00 μIU/mL | Standard Deviation 287.361 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: Prior to Glucose Load | 27.96 μIU/mL | Standard Deviation 14.366 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 90 minutes | 236.63 μIU/mL | Standard Deviation 168.861 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 30 minutes | 145.26 μIU/mL | Standard Deviation 106.082 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 60 minutes | 217.57 μIU/mL | Standard Deviation 181.115 |
| Placebo | Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 30 minutes | 170.83 μIU/mL | Standard Deviation 162.459 |
Secondary
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.
Time frame: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: Prior to Glucose Load | 15.60 mg/dL | Standard Deviation 5.578 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 30 minutes | 12.01 mg/dL | Standard Deviation 5.464 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 60 minutes | 6.63 mg/dL | Standard Deviation 3.925 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 90 minutes | 4.16 mg/dL | Standard Deviation 3.104 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 120 minutes | 2.52 mg/dL | Standard Deviation 1.378 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: Prior to Glucose Load | 16.62 mg/dL | Standard Deviation 4.162 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 30 minutes | 13.05 mg/dL | Standard Deviation 5.059 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 60 minutes | 7.41 mg/dL | Standard Deviation 3.462 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 90 minutes | 4.17 mg/dL | Standard Deviation 2.238 |
| Cenicriviroc 150 mg | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 120 minutes | 2.73 mg/dL | Standard Deviation 1.092 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 60 minutes | 8.23 mg/dL | Standard Deviation 3.376 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: Prior to Glucose Load | 17.44 mg/dL | Standard Deviation 5.62 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: Prior to Glucose Load | 14.60 mg/dL | Standard Deviation 5.089 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 30 minutes | 14.24 mg/dL | Standard Deviation 3.783 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 120 minutes | 4.05 mg/dL | Standard Deviation 2.749 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 60 minutes | 8.85 mg/dL | Standard Deviation 2.702 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 30 minutes | 12.84 mg/dL | Standard Deviation 3.59 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 90 minutes | 5.43 mg/dL | Standard Deviation 2.424 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 24: 90 minutes | 5.66 mg/dL | Standard Deviation 2.545 |
| Placebo | Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load | Week 12: 120 minutes | 4.08 mg/dL | Standard Deviation 2.057 |