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

Acta Dermato-Venereologica

Volumn 95, Issue 5, 2015, Pages 542-548

  Roblin, David ^a   Yosipovitch, Gil ^b   Boyce, Brent ^c   Robinson, John ^d   Sandy, James ^a   Mainero, Valentina ^e   Wickramasinghe, Ro ^a   Anand, Uma ^f   Anand, Praveen ^f  

^a Creabilis Ltd   (United Kingdom)

^b TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Great Lakes Research Group   (United States)

^d Synexus Limited   (United Kingdom)

^e Bioindustry Park Silvano Fumero   (Italy)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

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

Indexed keywords

ANTIPRURITIC AGENT; CAPSAICIN; CT 327; ENZYME INHIBITOR; NERVE GROWTH FACTOR; TROPOMYOSIN; TROPOMYOSIN RECEPTOR KINASE A; UNCLASSIFIED DRUG; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE A;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CALCIUM TRANSPORT; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; DRUG WITHDRAWAL; HUMAN; HUMAN TISSUE; IN VITRO STUDY; MAJOR CLINICAL STUDY; NONHUMAN; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; PSORIASIS; RANDOMIZED CONTROLLED TRIAL; RAT; SENSORY NERVE CELL; SIGNAL TRANSDUCTION; ADULT; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CHRONIC DISEASE; CLINICAL TRIAL; COMPARATIVE STUDY; COMPLICATION; DOSE RESPONSE; DRUG ADMINISTRATION; ENZYMOLOGY; FEMALE; FOLLOW UP; IMMUNOHISTOCHEMISTRY; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEEDLE BIOPSY; PATHOLOGY; PATHOPHYSIOLOGY; PATIENT SAFETY; TOPICAL DRUG ADMINISTRATION; TREATMENT OUTCOME;

ADMINISTRATION, TOPICAL; ADULT; BIOPSY, NEEDLE; CAPSAICIN; CELLS, CULTURED; CHRONIC DISEASE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; FOLLOW-UP STUDIES; HUMANS; IMMUNOHISTOCHEMISTRY; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PATIENT SAFETY; PROTEIN KINASE INHIBITORS; PRURITUS; PSORIASIS; RECEPTOR, TRKA; TREATMENT OUTCOME;

EID: 84928155371     PISSN: 00015555     EISSN: 16512057     Source Type: Journal    
DOI: 10.2340/00015555-2047     Document Type: Article

References (29)

1. Yosipovitch G, Goon A, Wee J, Chan YW, Goh CL. The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. Br J Dermatol 2000; 143: 969-973.
2. Prignano F, Ricceri F, Pescitelli L, Lotti T. Itch in psoriasis: epidemiology, clinical aspects and treatment options. Clin, Cosm Invest Derm 2009; 2: 9-13.
3. Reich A, Hrehorów E, Szepietowski JC. Pruritus is an important factor negatively influencing the well-being of psoriatic patients. Acta Derm Venereol 2010; 90: 257-263.
4. McCoy ES, Taylor-Blake B, Zylka MJ. CGRP-expressing sensory neurons respond to stimuli that evoke sensations of pain and itch. PLOS One 2012; 9: 1-11.
5. Han L, Ma C, Liu Q, Weng HJ, Cui Y, Tang Z, et al. A subpopulation of nociceptors specifically linked to itch. Nature Neuroscience 2013; 16: 174-182.
6. Rukweid RR, Main M, Weinkauf B, Schmelz M. NGF sensitizes nociceptors for cowhage- but not histamine induced itch in human skin. J Invest Dermatol 2013; 133: 268-270.
7. Raap U, Stander S, Metz M. Pathophysiology of itch and new treatments. Curr Opin Allergy Clin Immunol 2011; 11: 420-427.
8. Steinhoff M, Bienenstock J, Schmelz M, Maurer M, Wei E, Biro T. Neurophysiological, neuroimmunological and neuroendocrine basis of pruritis. J Invest Dermatol 2006; 126: 1705-1718.
9. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, et al. The cloned capsaicin receptor integrates multiple pain producing stimuli. Neuron 1998; 21: 531-543.
10. Winter J, Forbes CA, Sternberg J, Lindsay RM. Nerve growth factor regulates the adult rat cultured dorsal root ganglion neuron responses to the excitotoxin capsaicin. Neuron 1988; 1: 973-981.
11. Anand U, Otto WR, Casula MA, Day NC, Davis JB, Bountra C, et al. The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons. Neurosci Lett 2006; 399: 51-56.
12. Bley K, Anand P. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth 2011; 107: 490-502.
13. Anand P, Foley P, Navsaria HA, Sinicropi D, Williams- Chestnut RE, Leigh IM. Nerve growth factor levels in cultured human skin cells: effect of gestation and viral transformation. Neurosci Lett 1995; 184: 157-160.
14. Anand P. Neurotrophic factors and their receptors in human sensory neuropathies. Prog Brain Res 2004; 146: 477-492.
15. Bracci-Laudiero L, Pincelli C. Nerve growth factor is increased in psoriatic skin. J Invest Dermatol 1995; 105: 854-855.
16. Nakamura M, Toyoda M, Morahashi M. Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors. Br J Dermatol 2003; 149: 718-730.
17. Yamaguchi J, Aihara M, Kobayashi Y, Kambara T, Ikezawa Z. Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and psoriasis horny layer and effect of treatment on NGF in atopic dermatitis. J Dermatological Science 2009; 53: 48-54.
18. Anand U, Otto WR, Anand P. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons. Mol Pain 2010; 6: 1-11.
19. Anand U, Otto WR, Sanchez-Herrera D, Facer P, Yiangou Y, Korchev Y, et al. Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain 2008; 138: 667-680.
20. Reich A, Heisig M, Phan NQ, Taneda K, Takamori K, Takeuchi S, et al. Visual analogue scale: evaluation of the instrument for the assessment of pruritus. Acta Derm Venereol 2012; 92: 497-501.
21. Bautista D, Wilson S, Hoon M, Why we scratch an itch: the molecules, cells and circuits of itch. Nat Neurosci 2014; 17: 175-182.
22. Szepietowski C, Reich A, Wisnicka B. Itching in patients suffering from psoriasis. Acta Dermatovenerol Croat 2002; 10: 221-226.
23. Fleming C, Ganslandt C, Guenther L, Johannesson A, Buckley C, Simon JC, et al. Calcipotriol plus betamethasone dipropionate gel compared with its active components in the same vehicle and the vehicle alone in the treatment of psoriasis vulgaris: a randomised, parallel group, double blind, exploratory study. Eur J Dermatol 2010; 20: 465-471.
24. Gibson R, Robertson J, Mistry H, McCallum S, Fernando D, Wyres M, Yosipovitch G. Randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on pruritus induced by histamine, and cowhage challenge in healthy volunteers. PLOS One 2014; 9: 1-11.
25. Ghilardi J, Freeman K, Jimenez-Andrade J, Mantyh W, Bloom A, Bouhana K, et al. Sustained blockade of neurotrophin receptors TrkA, TrkB and TrkC reduces nonmalignant skeletal pain but not the maintenance of sensory and sympathetic nerve fibers. Bone 2011; 48: 389-398.
26. Indo Y. Nerve growth factor, pain, itch and inflammation: lessons from congenital insensitivity to pain with anhidrosis. Exp Rev Neurother 2010; 10: 1707-1724.
27. Roblin D, Wickramasinghe R, Yosipovitch G. Pruritus severity in patients with psoriasis is not correlated with psoriasis disease severity. J Am Acad Dermatol 2014; 70: 390-391.
28. Mamolo C, Harness J, Tan H, Menter A. Tofacitinib (CP- 690,550), an oral Janus kinase inhibitor, improves patientreported outcomes in a phase 2b, randomized, double-blind, placebo-controlled study in patients with moderate-tosevere psoriasis. J Eur Acad Dermatol Venereol 2013 Jan 7. [Epub ahead of print].
29. Lebwohl M, Bachelez H, Barker J, Girolomoni G, Kavanaugh A, Langley R, et al. Patient perspectives in the management of psoriasis: results from the populationbased Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol 2014; 70: 871-881.