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 language | English (US) |
|---|---|
| Pages (from-to) | 542-548 |
| Number of pages | 7 |
| Journal | Acta Dermato-Venereologica |
| Volume | 95 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 1 2015 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Topical TrkA kinase inhibitor CT327 is an effective, novel therapy for the treatment of pruritus due to psoriasis
T2 - Results from experimental studies, and efficacy and safety of CT327 in a phase 2b clinical trial in patients with psoriasis
AU - Roblin, David
AU - Yosipovitch, Gil
AU - Boyce, Brent
AU - Robinson, John
AU - Sandy, James
AU - Mainero, Valentina
AU - Wickramasinghe, Ro
AU - Anand, Uma
AU - Anand, Praveen
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Nerve growth factor
KW - Phase 2b
KW - Pruritus
KW - Psoriasis
KW - Tropomyosin-receptor kinase A
KW - Visual analogue scale
UR - http://www.scopus.com/inward/record.url?scp=84928155371&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928155371&partnerID=8YFLogxK
U2 - 10.2340/00015555-2047
DO - 10.2340/00015555-2047
M3 - Article
C2 - 25594427
AN - SCOPUS:84928155371
VL - 95
SP - 542
EP - 548
JO - Acta Dermato-Venereologica
JF - Acta Dermato-Venereologica
SN - 0001-5555
IS - 5
ER -