Efficacy and Safety Evaluation of Tirbanibulin Ointment in Adult Patients with Actinic Keratosis on the Face or Scalp: A Phase 3 Randomized Controlled Trial
- Trial ID
- 2023-505487-11-00
- Protocol
- M-14867-33
- Sponsor
- Almirall S.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **efficacy** of tirbanibulin 10 mg/g ointment compared to a vehicle on the clearance of actinic keratosis (AK) lesions after one course of treatment at Day 57 (Week 8) in adults with AK of the face or scalp. This is clinically relevant as it aims to determine the effectiveness of tirbanibulin in reducing AK lesions, which are precursors to skin cancer, thereby potentially preventing progression to malignancy.
Secondary objectives include:
- Assessing the efficacy of tirbanibulin 10 mg/g ointment compared to the vehicle on the clearance of AK lesions after up to two courses of treatment at Day 113 (Week 16).
- Evaluating the impact of tirbanibulin on patient-reported and investigator-reported measures of quality of life, cosmetic outcome, and treatment satisfaction after one and two courses of treatment.
- Evaluating the safety and tolerability of tirbanibulin compared to the vehicle up to Day 113 (Week 16).
- Assessing the long-term safety of tirbanibulin up to 48 weeks.
Participants
The clinical trial involves a total of **23 participants** diagnosed with **Actinic Keratosis** on the face or scalp. The study population includes both male and female adults aged 18 years and older. Participants were selected based on specific criteria, including having 4 to 12 clinically typical, visible, and discrete AK lesions on the face or balding scalp, with a treatment field measuring more than 25 cm² and up to approximately 100 cm². The trial population is required to avoid excessive sunlight or UV light exposure, including the use of tanning beds, during the study period. Participants must demonstrate the ability to understand the trial's purpose and risks, comply with the protocol, and provide written informed consent. The study includes both genders and considers vulnerable populations, ensuring comprehensive representation. Lifestyle considerations such as the use of effective contraception methods are mandated for women of childbearing potential and sexually active males with female partners who are of childbearing potential, to prevent pregnancy during and after the trial period.
Plans and Procedures
The clinical trial is a **Phase 3**, multicenter, randomized, double-blind, vehicle-controlled, parallel-group study designed to evaluate the efficacy and safety of **tirbanibulin** 10 mg/g ointment. The trial targets adult patients with **actinic keratosis** on the face or scalp, with a treatment field larger than 25 cm² and up to 100 cm². The primary objective is to assess the efficacy of tirbanibulin compared to a placebo vehicle in clearing actinic keratosis lesions after one course of treatment by Day 57 (Week 8). The trial is expected to commence recruitment on December 1, 2023, and conclude by December 31, 2024.
Participants will be randomly assigned to receive either the active treatment or placebo, with both groups blinded to the treatment allocation. The study involves several key visits: an initial screening visit to confirm eligibility, followed by treatment administration visits, and subsequent follow-up visits to monitor efficacy and safety. The end-of-study visit will occur at Day 113, or earlier if a second treatment course is required. The expected duration of participant involvement is approximately 113 days, with conditions for early termination including non-compliance with the study protocol or adverse events that necessitate withdrawal.
Inclusion criteria require participants to be 18 years or older, with a treatment field on the face or scalp containing 4 to 12 clinically typical, visible, and discrete actinic keratosis lesions. Participants must avoid excessive sunlight or UV exposure during the study. Women of childbearing potential must adhere to strict contraceptive measures and undergo regular pregnancy testing. Male participants with female partners of childbearing potential must also use contraception and refrain from sperm donation during and after the study period. The primary endpoint is the percent change from baseline in lesion count at Day 57, with secondary endpoints including the proportion of patients achieving partial or complete clearance of lesions by Day 57 and Day 113.
Treatment
The clinical trial involves the use of **Klisyri 10 mg/g ointment**, which contains the active substance **tirbanibulin**. This experimental medication is formulated as an ointment and is intended for **cutaneous use**. The dosage is specified as 10 mg/g, with a maximum daily dose of 10 mg/g. The treatment is applied once daily for a maximum period of 10 days. The ointment is manufactured by ALMIRALL, S.A., and is of chemical origin. The primary objective of the trial is to evaluate the efficacy of tirbanibulin in clearing actinic keratosis lesions.
In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is a smooth, creamy white to off-white ointment, free from foreign particles, and is provided in single-use packets containing 350 mg of the product. It shares the same qualitative composition as the active product but lacks the active substance, **tirbanibulin**. The placebo is also intended for cutaneous use and is applied in the same manner as the experimental ointment to ensure blinding in the study.
Efficacy
The efficacy of **tirbanibulin** 10 mg/g ointment in the treatment of actinic keratosis will be assessed in a Phase 3, multicentre, randomised, double-blind, vehicle-controlled, parallel-group study. The primary endpoint for evaluating efficacy is the percent change from baseline in lesion count at Day 57. Secondary endpoints include the proportion of patients achieving partial clearance (PC) and complete clearance (CC) of lesions at Day 57 and Day 113. PC is defined as ≥75% clearance in the treatment field (TF) at Day 57, while CC is defined as 100% clearance in the TF at Day 57. For patients receiving a second treatment course, PC by Day 113 is defined as ≥75% clearance at Day 113, and CC by Day 113 is defined as 100% clearance at Day 113.
Efficacy assessments will be conducted at specified timepoints, including Day 57 and Day 113, to evaluate the clearance of actinic keratosis lesions. The study will involve the application of tirbanibulin ointment to a treatment field larger than 25 cm² and up to 100 cm² on the face or scalp of adult patients. The efficacy parameters will be collected and analyzed to determine the effectiveness of the treatment compared to the vehicle. The study aims to provide comprehensive data on the efficacy of tirbanibulin ointment in achieving lesion clearance in patients with actinic keratosis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients with AK who are ≥18 years old
- Having a TF on the face or balding scalp (excluding lips, eyelids, and inside nostrils and ears) that: a) contains ≥4 to ≤12 clinically typical, visible, and discrete (non-confluent) AK lesions and b) measures more than 25 cm2 (eg, one cheek) and up to approximately 100 cm2 (eg, mid face)
- Willing to avoid excessive sunlight or UV light exposure, including the use of tanning beds, to the face or scalp during the study
- Women of childbearing potential (WOCBP), ie, fertile, defined as a female in the life period from menarche and until becoming post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (with hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months prior to Screening) must: • have a negative urine pregnancy test using a highly sensitive method at screening and on Day 1 prior to treatment administration, • be using highly effective methods of birth control (defined in Appendix 1) for at least 30 days or 1 menstrual cycle, whichever is longer, and until at least 30 days or 1 menstrual period, whichever is longer, after the last dose of investigational product, • agree to have pregnancy tests while in the study and at the end of the study (according to the Schedule of Assessments in Table 1), and • agree not to be egg (oocyte) donors while on study and until at least 30 days or 1 menstrual period, whichever is longer, after the last dose of investigational product.
- Sexually active males with female partners who are WOCBP must agree to use two forms of contraception, one of which must be barrier contraception, from Screening through 90 days after their last dose of study treatment. All non-sterile male patients must agree not to donate sperm or attempt conception from Screening through 90 days following their last dose of study treatment.
- Ability to understand the purpose and risks of the trial, willingness and ability to comply with the protocol, and provided written informed consent in accordance with institutional and regulatory guidelines.
Exclusion Criteria
- Presence in the TF of: a) Clinically atypical and/or rapidly changing AK lesions in the TF b) Hyperkeratotic or hypertrophic lesions, recalcitrant disease (defined as failure to respond to cryosurgery on 2 previous occasions) and/or cutaneous horn c) History of invasive SCC, Bowen’s disease, basal cell carcinoma (BCC), or other malignant tumours in the TF d) Any other dermatological disease that causes difficulty with examination
- Location of the TF is: • On any location other than the face or balding scalp • Within 5 cm of an incompletely healed wound • Within 5 cm of a suspected BCC or other neoplasms • Periorbital, lips, or nostrils
- Having a previous treatment with tirbanibulin 10 mg/g ointment
- Females who are pregnant or nursing or seeking to become pregnant
- Intention to use any concomitant medication that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication or therapy
- Anticipated need for inpatient hospitalization or inpatient surgery from Day 1 to Day 113
- A history of sensitivity and/or allergy to any of the ingredients in the study medication
- Patients with significant abnormalities on the medical history, physical examination (PE) findings, vital signs, clinical chemistry, or haematology results that in the judgment of the Investigator may interfere with the interpretation of the results.
- A skin disease (eg, atopic dermatitis, psoriasis, eczema) or condition (eg, scarring, open wounds) that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the patient to unacceptable risk by study participation
- Significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the Investigator, would expose the patient to unacceptable risk by study participation
- Participated in an investigational drug trial during which an investigational study medication was administered within 30 days or 5 half-lives of the investigational product, whichever is longer, before dosing in the current study
- Subject is vulnerable as defined in the ICH E6[R2] Guideline for GCP, as a subject whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. For example, a patient who is employee or a relative to an employee at the research site or the Sponsor.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Dec 2023 | 62 |
 Italy | Not Recruiting | 01 Dec 2023 | 76 |
 The Netherlands | Not Recruiting | 01 Dec 2023 | — |
 Poland | Not Recruiting | 01 Dec 2023 | 54 |
 Spain | Not Recruiting | 01 Dec 2023 | 54 |
| Netherlands | — | — | 23 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TIRBANIBULIN | Test | — | CUTANEOUS USE | 10 | 10 | SUB198081 |
Placebo of the new presentation of 350 mg/sachet drug product (hereafter referred as vehicle) is a smooth, creamy white to off-white ointment free from foreign particles, packed intact and
properly sealed containing the same qualitative composition as the active product but without the active substance. The vehicle will be provided in a single-use packets to contain 350 mg of
drug product. | Placebo | N/A | — | — | — | N/A |
Klisyri 10 mg/g ointment | Test | OINTMENT | CUTANEOUS USE | 10 | 10 | PRD9189852 |