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

David Roblin, Gil Yosipovitch, Brent Boyce, John Robinson, James Sandy, Valentina Mainero, Ro Wickramasinghe, Uma Anand, Praveen Anand

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)542-548
Number of pages7
JournalActa Dermato-Venereologica
Volume95
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Pruritus
Psoriasis
Phosphotransferases
Clinical Trials
Safety
Capsaicin
Therapeutics
Nerve Growth Factor Receptor
Sensory Receptor Cells
tropomyosin kinase
Visual Analog Scale
Research Personnel
Calcium

Keywords

  • Nerve growth factor
  • Phase 2b
  • Pruritus
  • Psoriasis
  • Tropomyosin-receptor kinase A
  • Visual analogue scale

ASJC Scopus subject areas

  • Dermatology

Cite this

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. / Roblin, David; Yosipovitch, Gil; Boyce, Brent; Robinson, John; Sandy, James; Mainero, Valentina; Wickramasinghe, Ro; Anand, Uma; Anand, Praveen.

In: Acta Dermato-Venereologica, Vol. 95, No. 5, 01.01.2015, p. 542-548.

Research output: Contribution to journalArticle

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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.",
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