Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Participant Eligibility
2.3. Assessments and Statistical Analyses
3. Results
3.1. Patient Enrolment, Demography and Baseline Characteristics
3.2. Safety
3.3. KX01 Concentration
3.4. Clinical Activity against Psoriasis
3.5. TAS and PGA Score Trend in Stage IV
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patients | Stage I | Stage II | Stage III | Stage IV |
---|---|---|---|---|
Parameter | KX01 0.01% + Placebo (N = 8) | KX01 0.1% + Placebo (N= 8) | KX01 1% (N = 6) | KX01 1% (N = 6) |
Age (years) | ||||
Mean (SD) | 55.48 (17.14) | 51.86 (18.14) | 49.53 (16.43) | 51.19 (9.31) |
Median (Min, Max) | 55.7 (33.4, 81.9) | 52.5 (30.5, 80.1) | 49.4 (27.8, 73.7) | 51.3 (38.0, 63.0) |
Sex, n (%) | ||||
Male | 7 (87.5) | 8 (100.0) | 4 (66.7) | 5 (83.3) |
Female | 1 (12.5) | 0 (0) | 2 (33.3) | 1 (16.7) |
Ethnic origin | ||||
Asian | 8 (100.0) | 8 (100.0) | 6 (100.0) | 6 (100.0) |
BMI (kg/m2) | ||||
Mean (SD) | 26.40 (4.04) | 26.34 (4.39) | 27.36 (2.54) | 24.66 (3.98) |
Median (Min, Max) | 27.16 (19.8, 32.6) | 26.64 (19.7, 32.2) | 26.13 (25.3, 30.7) | 25.10 (19.9, 30.9) |
Family history of psoriasis | ||||
Yes | 1 (12.5) | 4 (50.0) | 2 (33.3) | 3 (50.0) |
No | 7 (87.5) | 4 (50.0) | 4 (66.7) | 3 (50.0) |
Smoking habit | ||||
Yes | 1 (12.5) | 1 (12.5) | 1 (16.7) | 2 (33.3) |
No | 7 (87.5) | 7 (87.5) | 5 (83.3) | 4 (66.7) |
Baseline total TAS | ||||
Mean (SD) | 6.25 (1.06) | 7.00 (1.51) | 5.83 (1.60) | 6.50 (1.38) |
Median (Min, Max) | 7.00 (4.00, 7.00) | 7.50 (5.00, 9.00) | 6.00 (4.00, 8.00) | 6.50 (5.00, 8.00) |
Baseline PGA | ||||
Mean (SD) | 3.25 (0.75) | 3.88 (1.13) | 2.83 (0.75) | 3.50 (0.55) |
Median (Min, Max) | 3.00 (2.00, 4.00) | 4.00 (2.00, 5.00) | 3.00 (2.00, 4.00) | 3.50 (3.00, 4.00) |
Category | Stage I | Stage II | Stage III | Stage IV | ||||
---|---|---|---|---|---|---|---|---|
KX01 0.01% + Placebo (N = 8) | KX01 0.1% + Placebo (N = 8) | KX01 1% (N = 6) | KX01 1% (N = 6) | |||||
E | n (%) | E | n (%) | E | n (%) | E | n (%) | |
Overall adverse events | 9 | 5 (62.5) | 4 | 3 (37.5) | 9 | 4 (66.7) | 8 | 5 (83.3) |
TEAEs | 5 | 4 (50.0) | 3 | 2 (25.0) | 7 | 4 (66.7) | 8 | 5 (83.3) |
Related TEAEs | 1 | 1 (12.5) | 3 | 2 (25.0) | 2 | 2 (33.3) | 5 | 5 (83.3) |
Serious TEAEs | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) |
Related serious TEAEs | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) |
Severity TEAEs | ||||||||
Grade 1 | 3 | 3 (37.5) | 3 | 2 (25.0) | 6 | 4 (66.7) | 8 | 5 (83.3) |
Grade 2 | 1 | 1 (12.5) | 0 | 0 (0.0) | 1 | 1 (16.7) | 0 | 0 (0.0) |
Grade 3 | 1 | 1 (12.5) | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) |
TEAE leading to treatment discontinuation | 1 | 1 (12.5) | 1 | 1 (12.5) | 0 | 0 (0.0) | 0 | 0 (0.0) |
IMP-related TEAEs | ||||||||
Pain of skin | 1 | 1 (12.5) | 1 | 1 (12.5) | 1 | 1 (16.7) | 0 | 0 (0.0) |
Contact dermatitis | 0 | 0 (0.0) | 2 | 1 (12.5) | 1 | 1 (16.7) | 5 | 5 (83.3) |
Any TEAEs | ||||||||
Eczema | 1 | 1 (12.5) | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) |
Skin eruption | 1 | 1 (12.5) | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) |
Pain of skin | 1 | 1 (12.5) | 1 | 1 (12.5) | 1 | 1 (16.7) | 0 | 0 (0.0) |
Upper respiratory tract infection | 1 | 1 (12.5) | 0 | 0 (0.0) | 1 | 1 (16.7) | 1 | 1 (16.7) |
Oral herpes | 0 | 0 (0.0) | 0 | 0 (0.0) | 1 | 1 (16.7) | 0 | 0 (0.0) |
Contusion | 1 | 1 (12.5) | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) |
Contact dermatitis | 0 | 0 (0.0) | 2 | 2 (25.0) | 1 | 1 (16.7) | 5 | 5 (83.3) |
Flare-up of psoriasis | 0 | 0 (0.0) | 0 | 0 (0.0) | 1 | 1 (16.7) | 0 | 0 (0.0) |
Blood bilirubin increase | 0 | 0 (0.0) | 0 | 0 (0.0) | 1 | 1 (16.7) | 0 | 0 (0.0) |
Leukocytosis | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) | 1 | 1 (16.7) |
Ligament sprain | 0 | 0 (0.0) | 0 | 0 (0.0) | 0 | 0 (0.0) | 1 | 1 (16.7) |
Patients | Stage I | Stage II | Stage III | Stage IV | ||
---|---|---|---|---|---|---|
KX01 0.01% (N = 6) | Placebo (N = 2) | KX01 0.1% (N = 6) d | Placebo (N = 2) | KX01 1% (N = 6) | KX01 1% (N = 6) | |
TAS 50 a | ||||||
n | 8 b | 3 c | 5 | 2 | 6 | 6 |
Yes | 0 (0.0) | 0 (0.0) | 1 (0.0) | 0 (0.0) | 0 (0.0) | 3 (50.0) |
No | 8 (100.0) | 3 (100.0) | 4 (80.0) | 2 (100.0) | 6 (100.0) | 3 (50.0) |
PGA score of 0 or 1 and at least a two-grade improvement | ||||||
n | 8 | 3 | 5 | 2 | 6 | 6 |
Yes | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (33.3) |
No | 8 (100.0) | 3 (100.0) | 5 (100.0) | 2 (100.0) | 6 (100.0) | 4 (66.7) |
Disease relapse | ||||||
n | -- | 1 | 0 | 0 (0.0) | 1 (33.3) | |
Relapse | -- | 1 (100.0) | 0 (0.0) | 0 (0.0) | 1 (33.3) | |
Non-relapse | -- | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (66.7) |
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Hong, J.-B.; Wu, P.-Y.; Qin, A.; Huang, Y.-W.; Tseng, K.-C.; Lai, C.-Y.; Chan, W.-K.; Fang, J.; Cutler, D.L.; Tsai, T.-F. Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results. Pharmaceutics 2022, 14, 2159. https://doi.org/10.3390/pharmaceutics14102159
Hong J-B, Wu P-Y, Qin A, Huang Y-W, Tseng K-C, Lai C-Y, Chan W-K, Fang J, Cutler DL, Tsai T-F. Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results. Pharmaceutics. 2022; 14(10):2159. https://doi.org/10.3390/pharmaceutics14102159
Chicago/Turabian StyleHong, Jin-Bon, Po-Yuan Wu, Albert Qin, Yi-Wen Huang, Kuan-Chiao Tseng, Ching-Yu Lai, Wing-Kai Chan, Jane Fang, David L. Cutler, and Tsen-Fang Tsai. 2022. "Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results" Pharmaceutics 14, no. 10: 2159. https://doi.org/10.3390/pharmaceutics14102159
APA StyleHong, J.-B., Wu, P.-Y., Qin, A., Huang, Y.-W., Tseng, K.-C., Lai, C.-Y., Chan, W.-K., Fang, J., Cutler, D. L., & Tsai, T.-F. (2022). Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results. Pharmaceutics, 14(10), 2159. https://doi.org/10.3390/pharmaceutics14102159