Study Design:

Two identical, double-blind, randomized, vehicle-controlled clinical trials of 702 patients — 1:1 randomization. Treatment groups were comparable across all demographics and baseline characteristics, including AK lesion count and distribution on the face or scalp (4-8 clinically typical, visible, and discrete AK lesions in a contiguous 25-cm² area). Subjects received 5 consecutive days of once-daily treatment with either KLISYRI^® (n=353) or vehicle control (n=349) to the treatment field.^1,2

• In a separate, multicenter, open-label safety trial, 105 subjects were treated with KLISYRI^® once daily for 5 consecutive days in a 100 cm² treatment field on the face or scalp. Subjects enrolled had 4 to 12 clinically typical, visible, and discrete AK lesions. Subjects had an average age of 69 years (range 45 to 87 years), were Caucasian (100%), and predominately male (67%) with Fitzpatrick skin types II or III (92%).
• The safety of KLISYRI^® treatment in a 100 cm² treatment field was comparable to the previous controlled study results in a 25 cm² treatment field.

Efficacy Measurements:

The primary efficacy endpoint was complete (100%) clearance of AK lesions in the treatment area, defined by the proportion of subjects at Day 57 with no clinically visible AK lesions in the treatment area.¹

The secondary efficacy endpoint was the percentage of patients with partial clearance of AK lesions, defined as a reduction of at least 75% in the number of lesions within the application area at Day 57.¹

Study Results:

Complete clearance in trial 1 occurred in 44% of patients (77 of 175) in the tirbanibulin group and in 5% (8 of 176) of those in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 48; P<0.001); in trial 2, complete clearance occurred in 54% of the patients (97 of 178) in the tirbanibulin group and in 13% (22 of 173) of those in the vehicle group (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001).¹

Partial clearance in trial 1 occurred in 68% of the patients (119 of 175) in the tirbanibulin group and in 16% (29 of 176) of those in the vehicle group (difference, 52 percentage points; 95% CI, 43 to 60; P<0.001); in trial 2, partial clearance occurred in 76% of the patients (136 of 178) in the tirbanibulin group and in 20% (34 of 173) of those in the vehicle group (difference, 57 percentage points; 95% CI, 48 to 65; P<0.001).¹

PROAK was an observational, single-arm, prospective, multicenter, Phase IV study among 300 adult patients with AK on the face or scalp who initiated treatment with tirbanibulin (per clinical judgment of the Site Investigator) in real-world clinical practices in the US as part of routine care.¹

Patients and clinicians completed surveys and clinical assessments concerning the safety and effectiveness of tirbanibulin at baseline, Week 8 (timeframe for primary endpoints), and Week 24 (290 patients were included in the full analyses set).¹

The primary endpoint was patient-reported quality of life (QoL) in terms of self-perceived AK symptoms and impact of AK on emotional well-being and functioning, as assessed by the Skindex-16 survey at Week 8. Additional endpoints included (not exclusively) tirbanibulin satisfaction as assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM-9) and the Expert Panel Questionnaire (EPQ) at Week 8, treatment effectiveness assessed by Investigator’s Global Assessment (IGA) at Week 8, investigator rating of severity of photodamage at Weeks 8 and 24, frequency of documented adverse events (AEs), serious adverse events (SAEs), and local skin reactions (LSRs) during the first 8 weeks of the study observation period.¹

Limitations of the study include the potential for recall bias, reporting bias, selection bias, and other biases commonly seen in real-world and open-label studies. Approaches such as standardized study inclusion/exclusion criteria, consecutive sampling, and geographically diverse dermatology clinics with varied experience with topical field therapy were employed to minimize these biases.

The purpose of the PROAK study was to evaluate patient-reported outcomes (PROs) and clinician-reported outcomes (ClinROs) regarding efficacy and safety after a follow-up period of 24 weeks among adult patients with AKs on the face or scalp who were administered tirbanibulin in real-world community practices in the US.²