A Phase 3, Multicentre, Randomised, Double-blind, Vehicle-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Tirbanibulin 10 mg/g Ointment Applied to a Treatment Field Larger Than 25 cm2 and up to 100 cm2 in Adult Patients With Actinic Keratosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Almirall S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

21 Dec 2023 → 25 Nov 2025

Decision date (initial)

2023-11-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Almirall, S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy of tirbanibulin 10 mg/g ointment compared to vehicle on the clearance of AK lesions after 1 course of treatment at Day 57 (Week 8) in adults with AK of the face or scalp

Secondary objectives 4

1. To assess the efficacy of tirbanibulin 10 mg/g ointment compared to vehicle on the clearance of AK lesions after up to 2 courses of treatment at Day 113 (Week 16) in adults with AK of the face or scalp
2. To evaluate the impact of tirbanibulin 10 mg/g ointment compared to vehicle on patient-reported and Investigator-reported measures of quality of life, cosmetic outcome, and treatment satisfaction after 1 and 2 courses of treatment in adults with AK of the face or scalp
3. To evaluate the safety and tolerability of tirbanibulin 10 mg/g ointment compared to vehicle up to Day 113 (Week 16) in adults with AK of the face or scalp
4. To evaluate the long-term safety of tirbanibulin 10 mg/g ointment up to 48 weeks in adults with AK of the face or scalp

Conditions and MedDRA coding

Actinic Keratosis on the Face or Scalp

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients with AK who are ≥18 years old
2. 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)
3. Willing to avoid excessive sunlight or UV light exposure, including the use of tanning beds, to the face or scalp during the study
4. 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.
5. 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.
6. 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 12

1. 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
2. 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
3. Having a previous treatment with tirbanibulin 10 mg/g ointment
4. Females who are pregnant or nursing or seeking to become pregnant
5. 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
6. Anticipated need for inpatient hospitalization or inpatient surgery from Day 1 to Day 113
7. A history of sensitivity and/or allergy to any of the ingredients in the study medication
8. 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.
9. 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
10. 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
11. 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
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline in lesion count at Day 57

Secondary endpoints 4

1. Proportion of patients with PC at Day 57, defined as ≥75% clearance in the TF at Day 57
2. Proportion of patients with CC at Day 57, defined as 100% clearance in the TF at Day 57
3. Proportion of patients with PC by Day 113, defined as 100% clearance in the TF at Day 57 or, for patients receiving a second treatment course, ≥75% clearance at Day 113
4. Proportion of patients with CC by Day 113, defined as 100% clearance in the TF at Day 57 or, for patients receiving a second treatment course, 100% clearance at Day 113

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Almirall S.A.

Sponsor organisation

Almirall S.A.

Address

Ronda General Mitre 151

City

Barcelona

Postcode

08022

Country

Spain

Scientific contact point

Organisation

Almirall S.A.

Contact name

Tolga Baykal

Public contact point

Organisation

Almirall S.A.

Contact name

Estrella Garcia Alvarez

Third parties 11

Locations

5 EU/EEA countries · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications