1 Novartis Pharma AG, Basel, Switzerland.
2 Allergan plc, CA, USA.
3 University of Antwerp, Antwerp, Belgium.
4 Virginia Commonwealth University, Virginia, USA.
5 Northwestern University, IL, USA.
6 University of Chicago, IL, USA.
7 University of California at San Diego, California, USA.
8 Sorbonne Université, Hôpital Pitié Salpêtrière, ICAN, Paris, France.
9 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
10 Institute of Translational & Clinical Research, Faculty of Medical Sciences, Newcastle University, Newcastle NIHR Biomedical Research Center, & Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Electronic address: firstname.lastname@example.org.
Nonalcoholic steatohepatitis (NASH) is a multifactorial disease involving different contributing mechanisms, with no approved therapies so far. Tropifexor (TXR), a farnesoid X receptor agonist, and cenicriviroc (CVC), a chemokine receptor types 2/5 antagonist, target the steatotic, inflammatory, and/or fibrotic pathways involved in NASH.
TANDEM (CLJC242A2201J; NCT03517540) is a 48-week, phase 2b, randomized, double-blind, multicenter study in 200 adult patients with biopsy-proven NASH and liver fibrosis. Patients will be randomized in a 1:1:1:1 ratio to receive either TXR 140?μg once daily (qd), CVC 150?mg qd, TXR 140?μg?+?CVC 150?mg qd, or TXR 90?μg?+?CVC 150?mg qd. The study comprises a 48-week treatment period and 4?weeks of follow-up. The key inclusion criterion is presence of NASH with fibrosis stage F2/F3 as seen on screening liver biopsy or on historical liver biopsy performed within 6?months prior to screening.
The primary objective is evaluation of the safety and tolerability of combination therapy compared with the monotherapies over 48?weeks. The secondary objective is to evaluate efficacy as assessed by ≥1-point improvement in liver fibrosis versus baseline or resolution of steatohepatitis after 48?weeks.
TANDEM will evaluate the combination of TXR and CVC with respect to safety and efficacy outcomes related to improvement in fibrosis or resolution of steatohepatitis. Given the effects of TXR and CVC in multiple pathophysiological pathways associated with NASH, combination therapy is likely to show additional benefits compared with monotherapy.