ORION: Effects of Cenicriviroc on Insulin Sensitivity in Subjects With Prediabetes or T2DM and Suspected NAFLD

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.

Inclusion Criteria:

- Adult male and female subjects aged between 18-75 years

- Obesity as defined by BMI ≥ 30 kg/m2

- Evidence of prediabetes or type 2 diabetes mellitus based on Screening laboratory
values with at least one of the following criteria:

- Fasting plasma glucose (FPG) of 100 - 270 mg/dL (5.6 - 15.0 mmol/L)

- Hemoglobin A1c (HbA1c) of 5.7 - 10.0%

- Subjects receiving metformin alone or in combination with a sulfonylurea (glimepiride,
glipizide, glyburide, or gliclazide) must be on stable therapy for at least 90 days
prior to Screening.

- Suspected diagnosis of NAFLD warranting confirmation by liver biopsy

- AST and ALT ≤ 5 ULN

- Ability to understand and sign a written informed consent form

- Females of child-bearing potential and males participating in the study must agree to
use at least 2 approved barrier methods of contraception throughout the duration of
the study and for 3 months after stopping study drug. Females who are postmenopausal
must have documentation of cessation of menses for ≥ 12 months and serum follicle
stimulating hormone (FSH) ≥ 30 mU/mL

- Subjects receiving allowed concomitant medications need to be on stable therapy for 28
days prior to Baseline

Exclusion Criteria:

- Use of OHAs other than metformin or sulfonylureas, including but not limited to
thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists,
meglitinides, α-glucosidase inhibitors, colesevelam, bromocriptine, pramlintide or
basal insulin within 90 days prior to Screening or anticipated use during the trial

- Type 1 diabetes

- HBsAg positive

- HIV-1 or HIV-2 infection

- HCVAb positive

- Prior or planned liver transplantation

- Other known causes of chronic liver disease, including alcoholic liver disease

- History of cirrhosis and/or hepatic decompensation including ascites, encephalopathy
or variceal bleeding

- Alcohol consumption greater than 14 units/week

- Weight reduction through bariatric surgery or planned bariatric surgery during the
conduct of the study (including gastric banding)

- Any Grade ≥ 3 laboratory abnormality as defined by the National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE) Toxicity Grading Scale,
except subjects with Grade ≥ 3 dyslipidemia with triglyceride or cholesterol
elevations unless clinical assessment foresees an immediate health risk to the subject

- Serum albumin < 3.5 g/dL

- Serum creatinine levels ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females if subject is
receiving metformin

- Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 according to the
Modification of Diet in Renal Disease (MDRD) equation

- Platelet count < 100,000/mm3

- Hemoglobin < 12 g/dL for males or < 11 g/dL for females

- Females who are pregnant or breastfeeding

- Receiving ongoing therapy with any disallowed medication at Screening

- Allergy to the study drug or its components

- Any other clinically significant disorders or prior therapy that, in the opinion of
the investigator, would make the subject unsuitable for the study or unable to comply
with the dosing and protocol requirements