Investigation of the Efficacy and Tolerability of Topical Applied Tirbanibulin on Actinic Keratoses With Downward-directed Proliferation Patterns (Tir2401)

The aim of this study is to observe the influence of tirbanibulin on proliferation patterns of actinic keratoses (efficacy on proliferation score according to Schmitz et al.). For this purpose, tirbanibulin is applied in-label, proliferation is measured by LC-OCT at different time points and dermatohistopathology is performed (optionally) at the end. Local skin reactions to the product will also be recorded (tolerability).

Study Overview

• Status: Recruiting
• Conditions: Actinic Keratosis (AK)

Detailed Description

Actinic keratoses (AK) are premalignant skin changes of a cutaneous squamous cell carcinoma (SCC), which are often triggered by UV exposure. Clinically, they appear as small, rough, reddish, sandpaper-like patches, occasionally also as hyperkeratotic lesions. They are one of the most common reasons for dermatological consultations, and their incidence has been steadily increasing in recent years due to changes in leisure habits with increased UV exposure and demographic changes in the population, such as those observed in Germany.

While the mortality rate of squamous cell carcinoma of the skin is low, the persistence and recurrence of AK, which requires frequent treatment, is a challenge for both patients and healthcare systems.

There are numerous treatment options for AK, ranging from surgical and cryosurgical interventions to ablative laser treatments, topical and photodynamic therapies. These treatments can generally be categorized as lesion- or field-oriented.

Some AK show resistance to conventional therapies. This could possibly be due to different proliferation patterns of AK. Schmitz et al. established the PRO score, an instrument that describes the proliferation behavior of AK in a three-stage scale. This histological score is well validated and is increasingly used in histological diagnostics. New imaging techniques such as confocal line-field optical coherence tomography (LC-OCT) enable real-time assessment of histological parameters without the need for biopsies. In LC-OCT it is possible to detect the PRO Score of an AK in a few seconds.

Clinical parameters such as the Olsen grade, on the other hand, record the visible or palpable hyperkeratosis of an AK. However, the significance of hyperkeratosis for the risk of progression of AK to SCC is only of minor importance. Histological diagnostics and LC-OCT therefore make it possible to determine this risk more precisely.

Similarly, clinical scores such as the Olsen garde do not indicate which AKs are refractory to therapy, and which respond to therapy. One reason for this could be the proliferation behavior of the individual AK. Tirbanibulin, which primarily targets this cell proliferation, is a promising agent for the treatment of highly proliferative AK (PRO II and III). One aim is to observe its effects on basal proliferation after treatment, which can be assessed in real time using LC-OCT. This non-invasive method provides rapid evaluations within minutes. In addition to efficacy in proliferative AK, evaluation of the tolerability of tirbanibulin is crucial to contextualize its role in therapy. It is therefore of interest to determine whether increased skin reactions in proliferative AK correlate with improved clearance rates.

Tirbanibulin is a method frequently used in practice for the treatment of actinic keratoses. The application is quick with only 5 consecutive applications, results in only a minor local reaction and is nevertheless effective. In this study, various parameters such as local tolerance, the Olsen grade and the PRO score will be monitored using LC-OCT. Patients with clinically confirmed AK for whom in-label therapy with tirbanibulin is planned anyway will be included.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Thomas Dirschka, Prof. Dr. med.; Phone Number: +49(0)20262933736; Email: T.dirschka@centroderm.de
• Study Contact Backup: Name: Marcus Kuchner, Dr. med.; Phone Number: +49(0)20262933763; Email: m.kuchner@centroderm.de

Study Locations

• Germany
  • NRW
    • Wuppertal, NRW, Germany, 42287
      • Recruiting
      • CentroDerm
      • Contact: Thomas Dirschka, Prof. Dr. med.; Phone Number: +492026293370; Email: T.dirschka@centroderm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients from the medical office (Berufsausübungsgemeinschaft Prof. Dr. Dirschka und Priv.-Doz. Dr. Schmitz).

Description

Inclusion Criteria:

• male, female, diverse patients (> 18yo) who are capable of giving consent
• female patients are eligible if the patient is not a woman of childbearing potential (WOCBP) or if she is postmenopausal (cessation of menstruation >12 months) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, total hysterectomy)
• signed informed consent
• diagnosis of at least 1 non-hypertrophic, non-hyperkeratotic actinic keratosis of the scalp or face with Olsen Grade I and PRO II or III
• planned treatment of AK with Klisyri® before study start and indepently of the study
• the study participant is in good general condition for his or her age and does not currently have any active diseases that, in the opinion of the investigator, justify exclusion from the study

Exclusion Criteria:

• known or documented intolerance to any of the ingredients of Klisyri®
• any planned AK treatment other than Klisyri® in the treatment area
• treatment of actinic keratoses in the treatment area within the past 3 Months (e.g. photodynamic therapy, topical 5-FU, diclofenac, imiquimod, cryotherapy etc.)
• suspected invasive squamous cell cancer in the treatment area
• chronic wounds, erosions, pre-existing inflamed or infected skin with disruption of the epidermal barrier in the treatment area
• suspected non-compliance
• current or within the last 8 weeks given systemic cancer medication
• any other topical treatment against actinic keratosis in the treatment area within the past 12 weeks
• any contraindication according to the Summary of Product Characteristics (SmPC) of Klisyri®
• any systemic immunosuppressant given within the 8 weeks prior to the study (e.g. systemic prednisolone, azathioprine etc.)
• locally applied retinoids, steroids, or other prescribed externals in the 4 weeks prior to the start of the study in the treatment area that, in the opinion of the study physician, necessitate exclusion
• products containing glycolic or alpha-hydroxy acids applied locally in the treatment area in the last 4 weeks
• chemical peelings in the treatment area in the last 4 weeks
• simultaneous participation in a clinical trial
• participation in a clinical study within the last 30 days
• family members or colleagues of the investigator or the investigational team or the CRO
• patient is in a position or has a relationship with the investigator that presents a potential conflict of interest

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
- Improvement of the PRO score of the marker lesion at D57 (LC-OCT) and/or clearance in LC-OCT of marker lesion at D57	Measurement will be done by LC-OCT to detect the PRO Score of the actinic keratosis.	70 days after inclusion (57 days after visit 2)
assessment of local skin reaction grading scale at V2	Assessment of the local skin reaction via a 4-point-likert scaled measurement of erythema, scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration	14 days after baseline visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical clearance of marker lesion at visit 2	Clinical clearance of the previously marked actinic keratosis	14 days after baseline visit
Clinical clearance of marker lesion at visit 3	Clinical clearance of predefined actinic keratosis at visit 3	70 days after baseline
Improvement of PRO Score at V2	Improvement of PRO score at visit 2 in LC-OCT (line-field optical coherence tomography)	14 days after baseline
LC-OCT clearance of marker lesion at V2	Clearance of marker lesion at visit 2 in LC-OCT (line-field optical coherence tomography)	14 days after baseline
Histopathological clearance of marker lesion at V3	histopathological clearance of predefined AK at V3. Only applicable if histopathology was performed afterwards (in case of persisting AKs)	70 days after baseline

Collaborators and Investigators

• Sponsor: Thomas Dirschka

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: actinic keratosis; LC-OCT; klisyri; tirbanibulin; proliferating actinic keratosis; proliferating actinic keratoses
• Additional Relevant MeSH Terms: Neoplasms; Skin Diseases; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: CentroDerm_TIR24001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No