In a double-blind, placebo-controlled, phase 3 trial conducted across multiple nations, treatment involving Elafibranor exhibited substantially greater improvements in relevant biochemical markers of cholestasis compared to the placebo. The study involved the randomization of 161 patients to investigate the therapeutic potential of Elafibranor, an oral compound serving as a dual agonist for peroxisome proliferator-activated receptor (PPAR) α and δ, in the treatment of primary biliary cholangitis.

Subjects diagnosed with cholangitis, who demonstrated an unsatisfactory response to or experienced unacceptable noxious effects with ursodeoxycholic acid, were randomized in a 2:1 ratio. They were treated with either a daily dose of 80 mg Elafibranor or a placebo. The key endpoint was to achieve a biochemical response by week 52. This response was characterized as an alkaline phosphatase level lower than 1.67 times the upper limit of the normal range, with a drop of at least 15% from the baseline, along with normal levels of total bilirubin.

The major secondary endpoints included: (1) Achieving alkaline phosphatase normalization by week 52, and (2) Assessing changes in pruritus intensity from baseline through week 52 and week 24, estimated via the Worst Itch Numeric Rating Scale (WI-NRS, with scores ranging from 0 [no itch] to 10 [worst itch imaginable]). In 51% of subjects (55/108) treated with Elafibranor and in 4% (2/53) in the placebo group, the key endpoint (biochemical response) was witnessed. This illustrated a difference of forty-seven percentage points (95% confidence interval [CI], 32 to 57).

At week 52, the level of alkaline phosphatase normalized in 15% of subjects in the Elafibranor arm and none in the placebo arm. This reflected a difference of fifteen percentage points (95% CI, 6 to 23). The least-squares mean alteration from baseline through week 52 on the WI-NRS showed no profound inter-arm difference (−1.93 vs. −1.15; difference, −0.78; 95% CI, −1.99 to 0.42) for those experiencing moderate-to-severe pruritus (22 in placebo arm, 44 in Elafibranor arm).

Deleterious events occurring more commonly with Elafibranor than with placebo encompassed vomiting, diarrhea, nausea, and abdominal pain. To sum up, the administration of Elafibranor led to significantly more substantial improvements in relevant biochemical indicators of cholestasis compared to the placebo.