|
Frenette et al. (39)
|
86 |
A randomized, placebo-controlled trial |
Emricasan 25 mg/ twice daily for 3 months |
Placebo twice daily/3 months |
Patients were Child-Pugh class A or B with compensated or decompensated cirrhosis (clinical, radiological, or biochemical evidence), with MELD scores ranging from 11 to 18. |
Autoimmune hepatitis, active inflammatory bowel disease, hepatitis B-infected subjects on treatment for <3 months, hepatitis C-infected subjects planning to receive anti-hepatitis C virus (HCV) treatment, Child-Pugh class C, international normalized ratio (INR)≥2.5, platelets ≤20 x 109/L, hepatic encephalopathy grade III, serum creatinine ≥2 mg/dL, alcohol consumption >21 oz/week for males or 14 oz/week for females, variceal hemorrhage within 3 months of screening, and uncontrolled ascites |
3 months (primary outcome assessment point) |
12 cases (13.95%): Intervention (4 cases), and Placebo (8 cases) |
Emricasan reduced cCK-18 by -13% relative to placebo at 3 months (p=0.092) |
1- Emricasan significantly reduced serum levels of flCK-18 (P=0.02) and caspase (P<0.001) at 3 months compared to placebo.
2- No significant differences between Emricasan and placebo in mean MELD (P=0.466) or Child-Pugh scores (P=0.124) at 3 months.
3- No differences between Emricasan and placebo regarding total bilirubin, INR, or serum albumin at 3 months. |
|
Garcia-Tsao et al. (38)
|
263 |
A randomized, placebo-controlled trial |
Emricasan (5, 25, and 50 mg) twice daily for 48 weeks |
Placebo |
Patients with cirrhosis due to non-alcoholic steatohepatitis (NASH) and baseline HVPG ≥12 mmHg. |
Other causes of cirrhosis, compensated or decompensated (no more than one decompensating event) |
48 weeks |
13 cases at 24 weeks and 44 cases at 48 weeks |
There were no significant differences in ?HVPG for any emricasan dose (5, 25, 50) vs. placebo (- 0.21, -0.45, -0.58 mmHg, respectively) |
1- Biomarkers decreased significantly with emricasan at week 24 but returned to baseline levels by week 48.
2- New or worsening decompensating events (∼10% over median exposure of 337 days), progression in MELD and Child-Pugh scores, and treatment-emergent adverse events were similar among treatment groups. |
|
Gracia-Tsao et al. (25)
|
23 |
Open-label single-arm clinical trial |
Emricasan 25 mg twice daily for 28 days |
None |
Patients with compensated cirrhosis and PH (HVPG >5 mmHg). |
Patients <18, decompensated cirrhosis defined by clinically overt ascites (requiring diuretics), overt encephalopathy (grade II or higher and requiring therapy), or history of variceal hemorrhage. Other exclusions included Child-Pugh class C, other non-liver organ failure, total bilirubin >12 mg/dL, INR >2.5, platelets <20x109/L, overt hepatic encephalopathy of grade III or higher, serum creatinine >2 mg/dL, use of non-selective beta blockers, carvedilol or nitrates, known HIV infection, pancreatitis, portal vein thrombosis, subjects planning to receive anti-HCV therapy during the study, subjects with HBV on stable therapy for less than 3 months, or hepatocellular carcinoma. An attempt was made to primarily enroll subjects with a history of NASH and/or hepatitis C virus (HCV) related cirrhosis and portal hypertension. |
28 days |
1 case |
Serum cCK18 and caspase-3/7 decreased significantly |
There was no significant change in HVPG after emricasan (mean [SD] -1.1[4.57] mmHg). No significant changes in blood pressure or heart rate were noted after Emricasan treatment. |
|
Harrison et al. (24)
|
318 |
A randomized, placebo-controlled trial |
Emricasan 5 mg (107 cases) or 50 mg (106 cases) twice daily for 72 weeks |
Placebo (105 cases) twice daily for 72 weeks |
Subjects had definite NASH and NASH CRN fibrosis stage F1-F3. |
Not specified |
76 weeks |
33 patients: Intervention (21 cases), placebo (12 cases) |
Emricasan did not improve fibrosis without worsening of NASH (Emricasan 5 mg =11.2%; Emricasan 50 mg =12.3%; placebo =19.0%) |
Emricasan did not result in NASH resolution without worsening of fibrosis (Emricasan 5 mg =3.7%; Emricasan 50 mg =6.6%; placebo =10.5%). |
|
Mehta et al. (40)
|
23 |
A randomized, placebo-controlled, phase II trial |
High-dose Emricasan (25-50 mg, twice daily) group |
Placebo/low-dose Emricasan (5 mg, twice daily) group |
Patients (≥18 years of age) with stable compensated or decompensated cirrhosis, presenting with an acute deterioration of liver function and associated organ failure. Cirrhosis was diagnosed by clinical, radiological, and/or histological methods, while acute decompensation was defined as ≤6 weeks. |
Recent hospital admission (within 4 weeks) for a complication of cirrhosis, greater than two-organ failure, HIV infection, uncontrolled bacterial infection, pre-existing chronic kidney disease, autoimmune liver disease, active malignancy aside from hepatocellular carcinoma, need for mechanical ventilation, inability to obtain consent, and hemodynamic instability (including use of inotropes, aside from terlipressin for hepatorenal syndrome). |
28 days |
At 28 days, 14 cases: Intervention (7 cases), control (7 cases) |
Emricasan pharmacokinetics: 5 mg dose was associated with low plasma levels (<50 ng/ml), and 25 mg and 50 mg doses showed comparable pharmacokinetic profiles |
1- At day 7, no significant differences were noted between placebo/low-dose and high-dose Emricasan groups regarding mean differences in MELD and CLIF-C ACLIF scores, and cCK18/flCK18 (M30/M65).
2- The mean percent reduction in cCK18/M30 in high-dose Emricasan group was significantly higher than the placebo/low-dose group at day 2 (-41.9% vs 0, P=0.017) and day 4 (-48.8% vs -7.4%, P=0.017). |
|
Pockros et al. (21)
|
105 |
A non-randomized placebo-controlled trial |
Emricasan at various doses (5, 25, 50, 100, 200, and 400 mg) once, twice, or 3 doses/day [14 dosing groups] |
Placebo |
Patients with ALT or AST elevations between 1.5 and 10 times the upper limit of the normal range and fibrosis stages F0 through F3 on a liver biopsy performed within 36 months of enrollment. NASH was diagnosed with liver biopsies demonstrating at least 1 steatosis and ballooning hepatocytes with inflammation and fibrosis. |
Patients with cirrhosis diagnosed upon biopsy or decompensated liver disease |
35 days |
NR |
In patients with HCV, except for 5 mg emricasan, all other doses significantly lowered ALT and AST (p=0.0041 to p<0.0001 for various dosing groups) compared to placebo |
Reduction in aminotransferase activity was seen in patients with NASH but effects were not apparent in the small number of other liver diseases. |
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