Age
Adult
Eligibility
Key eligibility criteria
1. NASH cirrhosis
2. Without varices
3. CTP score <7
4. Clinical signals suggesting
portal hypertension, with
at least 2 of:
• thrombocytopenia
• spleen size ≥ 15 cm
• evidence of collaterals
by imagingInclusion Criteria:
1. Is male or female, ≥ 18 and ≤ 75 years of age at the time of Screening.
2. Is willing and able to provide written informed consent prior to the initiation of any
study-specific procedures.
3. Has evidence of portal hypertension, with at least 2 of the following:
a. platelet count <150,000/mm3
b. spleen size ≥ 15 cm (by documented MRI, CT scan, or ultrasound imaging)
c. collateral vessels (by documented MRI or ultrasound imaging or physical
examination, ie, caput medusae)
4. Has a history confirming NASH cirrhosis, with at least one of the following:
There is a historical liver biopsy showing cirrhosis with steatohepatitis. There is
no evidence for a competing etiology for the cirrhosis.
There is a historical liver biopsy showing steatohepatitis, and there is evidence of
cirrhosis from clinical or imaging data or a second liver biopsy showing cirrhosis
without all features of NASH (as the histological NASH lesions may have burnt
out). There is no evidence for a competing etiology. There is at least 1 co-existing
or history of metabolic comorbidity at Screening: obesity (with either body mass
index [BMI] ≥30 kg/m2 or waist circumference ≥102 cm [40 in, men] or ≥88 cm
[35 in, women], or by ethnically appropriate cutpoints); hypertension (either on
anti-hypertensive drug therapy for at least 1 year or systolic/diastolic BP
>140/80 mm Hg); Type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.5%, or on
anti-diabetic medication for at least 1 year); or dyslipidemia (triglycerides
≥150 mg/dL or on drug therapy for hypertriglyceridemia for at least 6 months;
high-density lipoprotein cholesterol ≤40 mg/dL [men] or ≤50 mg/dL [women]) to
corroborate a diagnosis of NAFLD.
There is a historical liver biopsy showing cirrhosis with steatosis but not
steatohepatitis. There is no evidence for a competing etiology. There are at least
2 co-existing (or history of) metabolic comorbidities (with obesity or diabetes
being one of them) to corroborate a diagnosis of NAFLD.
There is a historical liver biopsy showing steatosis but now with cirrhosis either
by physical examination, imaging, or biopsy. If there is a current biopsy, it does
not show evidence of steatosis or steatohepatitis as histological lesions may have
burned out. There is no evidence for a competing etiology. There are at least
2 co-existing (or history of) metabolic comorbidities (with obesity or diabetes
being one of them) to corroborate a diagnosis of NAFLD.
For patients without a historical liver biopsy with slides available for review by
the central study pathologist, a screening liver biopsy is required.
Note: All liver biopsy blocks and/or slides for eligibility assessments (including those
from historical biopsies) will be reviewed by the central study pathologist while the
subject is in Screening, and must meet definitions for diagnosis of either Definitive
cirrhosis (1a, 1b, and 1c) or Probable cirrhosis (2a, per Liver Forum criteria
(Appendix 2). Results from the central study pathologist must be available before the
subject is randomized.
5. Absence of HCC by valid imaging (liver ultrasound, triple phase CT or MRI of liver)
within 6 months prior to randomization. If no such imaging result is available, then it
should be performed as part of standard of care.
6. Patients with type 2 diabetes mellitus can be enrolled, if they are adequately controlled on
a stable dose or doses of antidiabetic medication(s) for at least 3 months before study
enrollment, and their screening HbA1c is ≤9.5%.
7. Patients on vitamin E or pioglitazone can be enrolled if they are on a stable dose and
regimen for at least 3 months before screening, and the dose is expected to be held
constant during the trial.
8. Patients on a statin can be enrolled if they are on a stable dose and regimen for at least
3 months before screeni
