Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment

Summary

The primary objectives of this study are to evaluate the effect of Obeticholic Acid treatment compared to placebo on 1) histological improvement and 2) liver-related clinical outcomes in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis.

Timeline

Start

2015-09-22

Primary completion

2023-09-15

Completion

2023-09-15

Outcome

Met primary endpoint

Stopped: “The FDA issued a CRL in response to Intercept's NDA for OCA for the treatment of NASH. Sponsor decided to terminate 747-303 before the planned completion date.”

registry analysis (other test); OCA 25 mg vs Placebo; p = 0.0444; Hazard Ratio (HR) 0.772 (95% CI 0.600 to 0.994); Log Rank NCT02548351 ↗

Publications

• Sanyal AJ, Loomba R, Anstee QM, Ratziu V, Kowdley KV, Rinella ME, Harrison SA, Resnick MB, Capozza T, Sawhney S, Shelat N, Younossi ZM. Utility of pathologist panels for achieving consensus in NASH histologic scoring in clinical trials: Data from a phase 3 study. Hepatol Commun. 2023 Dec 22;8(1):e0325. doi: 10.1097/HC9.0000000000000325. eCollection 2024 Jan 1.
• Rinella ME, Dufour JF, Anstee QM, Goodman Z, Younossi Z, Harrison SA, Loomba R, Sanyal AJ, Bonacci M, Trylesinski A, Natha M, Shringarpure R, Granston T, Venugopal A, Ratziu V. Non-invasive evaluation of response to obeticholic acid in patients with NASH: Results from the REGENERATE study. J Hepatol. 2022 Mar;76(3):536-548. doi: 10.1016/j.jhep.2021.10.029. Epub 2021 Nov 15.
• Younossi ZM, Stepanova M, Nader F, Loomba R, Anstee QM, Ratziu V, Harrison S, Sanyal AJ, Schattenberg JM, Barritt AS, Noureddin M, Bonacci M, Cawkwell G, Wong B, Rinella M; RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) Study Investigators. Obeticholic Acid Impact on Quality of Life in Patients With Nonalcoholic Steatohepatitis: REGENERATE 18-Month Interim Analysis. Clin Gastroenterol Hepatol. 2022 Sep;20(9):2050-2058.e12. doi: 10.1016/j.cgh.2021.07.020. Epub 2021 Jul 15.
• Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman Z, Bedossa P, Geier A, Beckebaum S, Newsome PN, Sheridan D, Sheikh MY, Trotter J, Knapple W, Lawitz E, Abdelmalek MF, Kowdley KV, Montano-Loza AJ, Boursier J, Mathurin P, Bugianesi E, Mazzella G, Olveira A, Cortez-Pinto H, Graupera I, Orr D, Gluud LL, Dufour JF, Shapiro D, Campagna J, Zaru L, MacConell L, Shringarpure R, Harrison S, Sanyal AJ; REGENERATE Study Investigators. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019 Dec 14;394(10215):2184-2196. doi: 10.1016/S0140-6736(19)33041-7. Epub 2019 Dec 5.
• Ratziu V, Sanyal AJ, Loomba R, Rinella M, Harrison S, Anstee QM, Goodman Z, Bedossa P, MacConell L, Shringarpure R, Shah A, Younossi Z. REGENERATE: Design of a pivotal, randomised, phase 3 study evaluating the safety and efficacy of obeticholic acid in patients with fibrosis due to nonalcoholic steatohepatitis. Contemp Clin Trials. 2019 Sep;84:105803. doi: 10.1016/j.cct.2019.06.017. Epub 2019 Jun 29.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Obeticholic Acid	Small molecule	10 mg	Oral
Subject	Obeticholic Acid	Small molecule	25 mg	Oral

Indications