Efficacy and Safety of Cryotherapy Followed by Tirbanibulin Ointment for Actinic Keratosis on the Scalp and Forehead (TIRBACRYO)

The aim of the study is to evaluate the efficacy and safety of a combined approach of cryotherapy and tirbanibulin for the treatment of actinic keratosis of the scalp and forehead, repeated every 4 months. A higher rate of complete response is expected with this combination compared to cryotherapy alone, as well as a better response with repeated treatment cycles.

Study Overview

• Status: Not yet recruiting
• Conditions: Keratosis; Actinic Keratoses
• Intervention / Treatment: Drug: Cryotherapy + Tirbanibulin

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject over 18 years old presenting with ≥ 8 typical actinic keratoses (AK), clinically visible or palpable, grade I or II, with at least 4 AK per hemiscalp,
• Participants who, in the investigator's judgment, are in good general condition (ECOG ≤ 2),
• The AK must be distributed in 2 non-overlapping areas, and of similar grades,
• Patient capable of understanding and adhering to the study visit schedule and other protocol requirements,
• Patient capable of understanding and voluntarily signing informed consent,
• Patient covered by social insurance,
• Patient willing to comply with all study procedures and duration,
• Women of childbearing potential must:

Have a negative pregnancy test at screening and during the treatment period,

Use an effective contraceptive method throughout the study participation. Menopausal women (absence of menstruation for at least one year without other medical cause) or surgically sterile women (tubal ligation, hysterectomy, or bilateral oophorectomy) may be enrolled.

Exclusion Criteria:

• Clinically atypical and/or rapidly evolving actinic keratoses (AK) in the treatment area, and grade 3 AK according to Olsen classification,

• A defined treatment area that would be:

  1. Located somewhere other than the scalp and/or forehead,
  2. Within 5 cm of a wound that is not fully healed or a lesion suspicious for carcinoma,
• Prior treatment with tirbanibulin,
• Treatment with 5-fluorouracil (5-FU), imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other treatments for actinic keratoses in the treatment area or within 2 cm around this area within 6 weeks prior to the screening visit,

• Use of the following therapies within 2 weeks prior to the screening visit:

  1. Therapeutic or cosmetic procedures (e.g., liquid nitrogen application, surgical excision, dermabrasion, medium or deep chemical peeling, laser resurfacing) in the treatment area or within 2 cm around the selected treatment area,
  2. Therapeutic products containing acids (e.g., salicylic acid, fruit acids), topical retinoids, or light peels in the treatment area or within 2 cm around the selected treatment area,
• Allergy to tirbanibulin or any of its components.
• Any condition causing a risk of poor compliance,
• Administrative reasons: inability to receive informed information, inability to participate in the entire study, lack of social security coverage, refusal to sign the consent form,
• Women of childbearing potential who refuse to use an effective contraceptive method,
• Pregnant women, women planning to become pregnant, and breastfeeding women,
• Persons deprived of liberty by judicial or administrative decision.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Cryotherapy + Tirbanibulin : Tirbanibulin ointment applied once daily for 5 days, repeated 3 times (every 4 months)	Drug: Cryotherapy + Tirbanibulin; Tirbanibulin ointment applied once daily for 5 days, repeated 3 times (every 4 months); Other Names: Cryotherapy + placebo
Placebo Comparator: Control group; Cryotherapy + placebo : Tirbanibulin ointment applied once daily for 5 days, repeated 3 times (every 4 months)	Drug: Cryotherapy + Tirbanibulin; Tirbanibulin ointment applied once daily for 5 days, repeated 3 times (every 4 months); Other Names: Cryotherapy + placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clearance of actinic keratosis	Complete clearance rate of actinic keratoses at 8 months. A complete response corresponds to the absence of clinically detectable actinic keratosis in the treated area.	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the 12-month effectiveness of a combined approach using cryotherapy and tirbanibulin.	Complete Clearance of Actinic Keratosis at 12 months. A complete response corresponds to the absence of clinically detectable actinic keratosis in the treated area.	12 months
To evaluate the reduction in the number of actinic keratoses after 2 treatment cycles.	Partial clearance rate (75% reduction in the number of actinic keratoses) at 8 months.	8 months
To evaluate the reduction in the number of actinic keratoses after 3 treatment cycles.	Partial clearance rate (75% reduction in the number of actinic keratoses) at 12 months.	12 months
To evaluate the reduction in the need for cryotherapy with tirbanibulin.	Number of cryotherapy sessions performed over the entire follow-up period.	12 months
To describe the safety and tolerability by treated side at each follow-up visit.	Safety: Local skin reactions assessed throughout the study	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Almirall, SAS

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: September 23, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Actual): December 9, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Actinic Keratosis; Cryotherapy; Field cancerization; Tirbanibulin; Squamus cell carcinoma; Skin carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Skin Diseases; Precancerous Conditions; Skin and Connective Tissue Diseases; Keratosis, Actinic; Keratosis; Therapeutics; Cryotherapy; tirbanibulin
• Other Study ID Numbers: 2023_0127

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No