Efficacy and safety of piclidenoson in plaque psoriasis: Results from a randomized phase 3 clinical trial (COMFORT-1).
J Eur Acad Dermatol Venereol
; 38(6): 1112-1120, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38279575
ABSTRACT
OBJECTIVE:
A3 adenosine receptor (A3AR) is overexpressed in the skin and peripheral blood mononuclear cells of psoriasis patients. We investigated the efficacy/safety of piclidenoson (CF101), an orally bioavailable A3AR agonist that inhibits IL-17 and IL-23 production in keratinocytes, in moderate-to-severe plaque psoriasis.METHODS:
The randomized, placebo- and active-controlled, double-blind phase 3 COMFORT-1 trial randomized patients (3332) to piclidenoson 2 mg BID, piclidenoson 3 mg BID, apremilast 30 mg BID or placebo. At Week 16, patients in the placebo arm were re-randomized (111) to piclidenoson 2 mg BID, piclidenoson 3 mg BID or apremilast 30 mg BID. The primary end point was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI-75) at Week 16 versus placebo.RESULTS:
A total of 529 patients were randomized and received ≥1 dose of study medication (safety population). The efficacy analysis population for the primary end point included 426 patients (piclidenoson 2 mg BID, 127; piclidenoson 3 mg BID, 103; apremilast, 118; placebo, 78). Piclidenoson at 2 and 3 mg BID exhibited similar efficacy. The primary end point was met with the 3 mg BID dose PASI 75 rate of 9.7% versus 2.6% for piclidenoson versus placebo, p = 0.037. The PASI responses with piclidenoson continued to increase throughout the study period in a linear manner. At week 32, analysis in the per-protocol population showed that a greater proportion of patients in the piclidenoson 3 mg BID arm (51/88, 58.0%) achieved improvement from baseline in Psoriasis Disability Index (PDI) compared to apremilast (59/108, 55.1%), and the test for noninferiority trended towards significance (p = 0.072). The safety/tolerability profile of piclidenoson was excellent and superior to apremilast.CONCLUSIONS:
Piclidenoson demonstrated efficacy responses that increased over time alongside a favourable safety profile. These findings support its continued clinical development as a psoriasis treatment (ClinicalTrials.gov identifier NCT03168256).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Talidomida
Tipo de estudo:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article