title: Topical TrkA Kinase Inhibitor CT327 is an Effective, Novel Therapy for the Treatment of Pruritus due to Psoriasis: Results from Experimental Studies, and Efficacy and Safety of CT327 in a Phase 2b Clinical Trial in Patients with Psoriasis.
abstract: Pruritus is an important symptom in psoriasis with no targeted treatment. Tropomyosin-receptor kinase A (TrkA) is associated with pruritus and psoriatic plaque formation. We report the efficacy of a TrkA inhibitor, CT327, on pruritus in psoriasis. A randomised, double-blind, vehicle-controlled Phase 2b clinical trial was conducted in 160 subjects. No effect was found on psoriasis severity using Investigator's Global Assessment (primary endpoint). However, clinically and statistically significant reductions in pruritus were observed in the 108 patient subset reporting at least moderate pruritus at baseline (37.1 mm visual analogue scale improvement (95% CI [-37.5, -6.2], p = 0.0067) for lowest dose; secondary endpoint). Significant modified Psoriasis Area and Severity Index reductions were found in this subset (p < 0.05). Experiments exploring capsaicin-mediated calcium influx, important in pruritus signalling, were performed in sensory neurons. CT327 inhibited capsaicin responses, indicating action at the nerve growth factor-TrkA-TRPV1 pathway. TrkA is a key target in pruritus, and CT327 has potential to become an effective and safe first-in-class treatment.
authors.affiliation: Creabilis Limited, 6 Denne Hill Business Centre, Canterbury CT46HD, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Roblin
authors.forename: Gil
authors.initials: G
authors.lastname: Yosipovitch
authors.forename: Brent
authors.initials: B
authors.lastname: Boyce
authors.forename: John
authors.initials: J
authors.lastname: Robinson
authors.forename: James
authors.initials: J
authors.lastname: Sandy
authors.forename: Valentina
authors.initials: V
authors.lastname: Mainero
authors.forename: Ro
authors.initials: R
authors.lastname: Wickramasinghe
authors.forename: Uma
authors.initials: U
authors.lastname: Anand
authors.forename: Praveen
authors.initials: P
authors.lastname: Anand
mesh_terms: D000287:Administration, Topical; D000328:Adult; D001707:Biopsy, Needle; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D061214:Patient Safety; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011537:Pruritus / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D020917:Receptor, trkA / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D020917:Receptor, trkA; D002211:Capsaicin