A randomized, double-blind, multicenter, phase 2b study to evaluate the safety and efficacy of a combination of tropifexor and cenicriviroc in patients with nonalcoholic steatohepatitis and liver fibrosis: Study design of the TANDEM trial

Autor: Quentin M. Anstee, Marcos Pedrosa, Laurent Fischer, Sven Francque, Michael Charlton, Jossy Kochuparampil, Mary E. Rinella, Arun J. Sanyal, Star Seyedkazemi, Rohit Loomba, Sujata Vaidyanathan, Vlad Ratziu
Rok vydání: 2020
Předmět:
Liver Cirrhosis
Agonist
Oncology
medicine.medical_specialty
Combination therapy
Receptors
CCR2
medicine.drug_class
Receptors
Cytoplasmic and Nuclear
03 medical and health sciences
chemistry.chemical_compound
Clinical Trials
Phase II as Topic
0302 clinical medicine
Double-Blind Method
Non-alcoholic Fatty Liver Disease
Fibrosis
Internal medicine
medicine
Humans
Multicenter Studies as Topic
Pharmacology (medical)
Benzothiazoles
030212 general & internal medicine
Randomized Controlled Trials as Topic
030505 public health
medicine.diagnostic_test
business.industry
Imidazoles
Isoxazoles
General Medicine
medicine.disease
Treatment Outcome
Tolerability
chemistry
Sulfoxides
Liver biopsy
CCR5 Receptor Antagonists
Drug Therapy
Combination
Farnesoid X receptor
Human medicine
Steatohepatitis
0305 other medical science
business
Cenicriviroc
Zdroj: Contemporary clinical trials
ISSN: 1551-7144
DOI: 10.1016/j.cct.2019.105889
Popis: Background 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. Design 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. Objectives 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. Summary 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.
Databáze: OpenAIRE
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