Related Experiment Video
Updated: Nov 18, 2025
A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
Published on: September 20, 2019
Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis
Andrew Blauvelt1, Steven Kempers1, Edward Lain1
1From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).
Background:
The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.
Methods:
In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm2 contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (≥75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]).
Results:
A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved.
Conclusions:
In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).
Insights
Tirbanibulin ointment effectively treated actinic keratosis, with significant lesion reduction observed. However, local skin reactions were common, and lesion recurrence occurred within a year, necessitating further research.
Area of Science:
- Dermatology
- Oncology
- Pharmacology
Background:
- Actinic keratosis (AK) is a precancerous skin lesion that can progress to squamous-cell carcinoma.
- Tirbanibulin, a novel inhibitor of tubulin polymerization and Src kinase signaling, is being evaluated for topical AK treatment.
Purpose of the Study:
- To assess the efficacy and safety of topical tirbanibulin versus vehicle for treating actinic keratosis on the face or scalp.
- To evaluate lesion clearance rates and recurrence incidence following tirbanibulin treatment.
Main Methods:
- Two identical double-blind, randomized trials enrolled adults with AK on the face or scalp.
- Participants applied either tirbanibulin or vehicle ointment once daily for 5 days to a defined treatment area.
- Primary endpoint: complete lesion reduction at day 57; secondary endpoint: partial lesion reduction; recurrence assessed at 1 year.
Main Results:
- Complete clearance of AK lesions was significantly higher in the tirbanibulin group compared to vehicle (44% vs. 5% in Trial 1; 54% vs. 13% in Trial 2).
- Partial clearance rates were also significantly greater with tirbanibulin.
- Common local reactions included erythema (91%) and flaking (82%); application site pain (10%) and pruritus (9%) were reported.
Conclusions:
- Topical tirbanibulin demonstrated superior efficacy over vehicle for AK treatment at 2 months.
- The treatment was associated with transient local skin reactions and a notable rate of lesion recurrence at 1 year.
- Further trials comparing tirbanibulin with existing therapies and with longer follow-up are warranted.
Related Concept Videos
01:11Clinical Trials: Overview
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...