S1400 The Complexity of NASH Cirrhosis Clinical Trials: Screen Failure Reasons and Baseline Patient Characteristics

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Introduction: Patients with NASH cirrhosis has the highest likelihood of developing major adverse liver related events and an unmet need in terms of therapeutic options. Several drugs are being tested in patients with NASH cirrhosis in phase 2 trials. Screen failure (SF) reasons in non-cirrhotic NASH trials have been described; however, limited data exists on the reason for screen failure reasons in NASH cirrhosis trials. The aim of this study was to understand the reasons for screen failure in 5 NASH cirrhosis trials and to describe the patient's characteristics of both screens failed subjects and those who randomised. Methods: Data on patients who were presented for screening visits for five phase 2 NASH cirrhosis trials at one research site were analysed. The reasons for screen failure were divided into 4 major categories: 1. Biopsy, 2. Laboratory tests, 3. Imaging tests, 4. Other. Baseline characteristics including demographics, clinical history, lab values, findings from imaging tests and biopsy were collected. Characteristics of patients that screen failed were compared to those who randomised using 2-sided t-test, p value < 0.05 was considered statistically significant. Results: 68 patients were included in the analysis. 23 randomised (33.8%) and 45 screen failed (66.17%). The mean age was 57.98 years with 45% (31) of the population being male. Mean BMI in the whole population was 38.38 Kg/m2. 51.47% (35) of the patients were found to have type 2 diabetes. The reasons for screen failure were as follows: 4 (8.8%) on biopsy, 12 (26.6%) on labs, 11 (24.4%) in imaging tests, 15 (33.3%) for other reasons. The top 4 causes included in the other category were patients outside of the screening window, using prohibited medications, subject dropping out and presence of esophageal varices. There was no significant difference between the screen failure group and the randomised group in terms of platelet count, INR, bilirubin, FIB4 score and AGILE4 score (p > 0.05 for all). (Figure) Conclusion: NASH cirrhosis trials have similar screen failure rates compared to non-cirrhotic trials; however, the reasons for screen failure are different. In NASH cirrhosis trials, fewer patients screen failed because of not meeting histologic criteria on liver biopsy which has been the major reason for screen failure in non-cirrhotic trials. Baseline laboratory and imaging tests were not different between patients who screen failed and those who randomised. (Table)Figure 1.: Minor causes of screen failure Table 1. - Comparison chart showing basic characteristics of randomised and screen failure population 2 sided T Test Mean Mean Mean Total Population Randomised population Screen Failure population T-Test Age 58.31 60.95 56.88 BMI 37.38 39.88 37.05 Hba1C 6.42 6.43 6.46 % Diabetes 52.90% 48.50% 51.40% Platelets 177.23 159.26 187.30 0.13 Bilirubin 0.795 0.83 0.76 0.52 INR 1.13 1.15 1.12 0.24 kPa 23.31 24.03 22.24 0.79 Agile 4 0.44 0.518 0.42 0.23 CAP score 302.35 310.33 297.57 0.59 Fib 4 3.12 2.95 3.41 0.53