A Phase 4, Multi-centre, Randomized, Evaluator-blinded, Active-controlled Study to Determine the Incidence of Squamous Cell Carcinoma and Evaluate the Long-term Safety of Tirbanibulin 10 mg/g Ointment and Diclofenac Sodium 3% Gel for the Treatment of Adult Patients With Actinic Keratosis on the Face or Scalp

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

24 Oct 2022 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Almirall S.A.

External identifiers

EU CT number

2024-514394-22-00

EudraCT number

2021-004349-18

ClinicalTrials.gov

NCT05387525

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the incidence of biopsy-confirmed invasive SCC in the selected TF after administration of topical tirbanibulin 10 mg/g
ointment or diclofenac sodium 3% gel over the 3-year study period.

Secondary objectives 2

1. To evaluate the safety of topical tirbanibulin 10 mg/g ointment and diclofenac sodium 3% gel over the 3-year study period
2. To evaluate the effect of tirbanibulin 10 mg/g ointment treatment patientreported measures of quality of life, cosmetic outcome, and treatment satisfaction

Conditions and MedDRA coding

Actinic Keratosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female and ≥18 years old
2. A TF on the face or scalp (excluding lips, eyelids, ears, and inside the nostrils), that: • Is a contiguous area measuring 25 cm2, • Contains 2 to 8 clinically typical, visible, and discrete AK lesions, and • Has an overall clinical picture that is consistent with Olsen grade 1 (see Appendix 3 of the protocol)
3. If a 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), she must: • Have a negative urine pregnancy test using a highly sensitive method at screening and on Day 1 prior to treatment administration. • Be using effective methods of birth control. • 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 of the protocol)
4. Patients should be willing to avoid sunlight or UV light exposure, including the use of tanning beds, to the face or scalp during the study
5. Patients should have the ability to understand the purpose and risks of the study, willingness and ability to comply with the protocol, and provide written informed consent in accordance with institutional and regulatory guidelines

Exclusion criteria 17

1. The location of the TF is: a) On any location other than the face or scalp. b) Within 5 cm of an incompletely healed wound. c) Within 10 cm of a suspected basal cell carcinoma (BCC) or other neoplasm. d) On the lips, eyelids, ears, or inside the nostrils, periorbital, perioral, or the skin surrounding the nostrils.
2. Presence in the TF of: a) Clinically atypical and/or rapidly changing AK lesions b) Hyperkeratotic or hypertrophic lesions, recalcitrant disease (had cryosurgery on 2 previous occasions), and/or cutaneous horn. c) Confluent AK lesions (ie, non-discrete lesions, as per inclusion criterion 2). d) Persisting AK lesions at the screening visit following topical treatment with diclofenac sodium 3% gel.
3. History of any malignant skin tumour in the TF or history of skin tumour in any region of the body which has metastasized or in which metastasis within the study period is likely.
4. History of any malignant tumour with systemic antitumor treatment (including radiotherapy) within 12 weeks prior to the Screening Visit or systemic antitumor treatment is expected while on the study.
5. Immunocompromised patients, including patients with a history of chronic systemic lymphoma or chronic myeloid leukaemia, or organ transplant recipients.
6. Any other dermatological disease that causes difficulty with examination within the treatment area
7. Anticipated need for inpatient hospitalization or inpatient surgery during the study.
8. Previous treatment with tirbanibulin 10 mg/g ointment in the selected TF.
9. Treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other topical treatments for AK within the TF or within 2 cm of the TF, within 8 weeks prior to the Screening Visit.
10. Use of the following therapies and/or medications within 4 weeks prior to the Screening Visit: a) Treatment with cytotoxic drugs (eg, cyclophosphamide, vinblastine, chlorambucil, methotrexate) b) Treatment with systemic medications that modulate and/or suppress the immune system (eg, cyclosporine, prednisone, methotrexate, alefacept, infliximab, interferons or interferon inducers) c) Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene)
11. Use of the following therapies and/or medications within 2 weeks prior to the Screening Visit: a) Cosmetic or therapeutic procedures (eg, use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) within the TF or within a 2 cm margin of the selected TF. b) Acid-containing therapeutic products (eg, salicylic acid or fruit acids, such as alpha and beta-hydroxyl acids and glycolic acids), topical retinoids, or light chemical peels within the TF or within a 2 cm margin of the selected TF. c) Topical steroids within the TF or within a 2 cm margin of the selected TF. d) Artificial tanners within the TF or within a 5 cm margin of the selected TF
12. History of sensitivity and/or allergy to any of the ingredients in the study medications to tirbanibulin, diclofenac, or nonsteroidal anti-inflammatory drugs (ie, NSAIDs).
13. 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.
14. 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
15. Females who are pregnant or nursing or who are intending to become pregnant
16. Participated in an investigational drug study during which an investigational study medication was administered within 30 days or 5 half-lives of the investigational product, whichever is longer, prior to screening
17. Patient who is an employee or a relative to an employee at the research site or Almirall

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with histologically confirmed invasive SCC in the TF over the 3-year study period.

Secondary endpoints 10

1. AEs and SAEs over 3 years
2. Proportion of patients with any other skin cancer (other than SCC) in the TF over the 3-year study period
3. Time to occurrence of invasive SCC from baseline in the TF.
4. Proportion of patients requiring rescue treatment after 1 treatment course.
5. Proportion of patients requiring rescue treatment at any time during the study.
6. Proportion of patients with no lesions after treatment of the first recurrence with tirbanibulin during the first 52 weeks.
7. Other safety assessments (vital signs, PE) over 3 years.
8. Change from baseline in Skindex-16 overall and for all three domain scores (Symptoms, Emotions, and Functioning) by arm and by visit.
9. Cosmetic outcome by arm and by visit.
10. Treatment Satisfaction Questionnaire for Medication transformed scores by arm and by visit.

Investigational products

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

Test 1

Comparator 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

08017

Country

Spain

Scientific contact point

Organisation

Almirall S.A.

Contact name

Global Clinical Leader

Public contact point

Organisation

Almirall S.A.

Contact name

Global Clinical Operations

Third parties 12

Locations

5 EU/EEA countries · 44 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

Documents 6 files

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

Application history

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