Exploratory study to determine the tolerability and effectiveness of Tirbanibulin in the treatment of Actinic Cheilitis - Cheilitis trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Technische Universitat Dresden

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

26 Sep 2023 → 14 Nov 2024

Decision date (initial)

2023-07-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

Investigation of the effectiveness of Tirbanibulin (Klisyri) after five-day-application in patients with Actinic Cheilitis (healing) by measuring the reduction of the affected area.

Secondary objectives 7

1. Patient’s self-assessment regarding the occurrence of burning / stabbing pain, scabs, blisters/pustules, erosions/ulcerations, swelling and oozing (study subject self-assessment).
2. To determine the tolerability of the therapy (occurrence of AEs, SAEs).
3. To determine the tolerability of the therapy by means of investigator’s assessment of erythema, occurrence of scabs, blisters/pustules, erosions/ulcerations, swelling and oozing (local skin reaction score).
4. To determine life quality by means of the oral health DLQI-score.
5. To determine the tolerability of Tirbanibulin when administered on the lip(s) by means of local skin reaction score, study subject self-assessment (individual and total scores), oral health DLQI score.
6. To evaluate the visibility of histological criteria of Actinic Cheilitis in the imaging techniques used: optical coherence tomography, confocal laser scanning microscopy, line-field confocal optical coherence tomography (factors: presence/absence of thickening of the epidermis, increase in signal penetration, disruption of the Stratum corneum, visibility of the dermoepidermal junction zone, atypical Keratinocytes, Parakeratosis, erosion/ulceration, pigmentation of the basal epidermis layers, involvement of the annexes).
7. To compare the diagnostic criteria of the non-invasive imaging methods (optical coherence tomography, confocal laser scanning microscopy and line-field confocal optical coherence tomography) with regards to presence/absence of criteria of Actinic Cheilitis, imaging quality, diagnostic certainty before and after therapy. The imaging quality (excellent, good, moderate, poor) and the confidence (diagnostic certainty in 0-100%, whereas 100% equals a definite diagnosis of Actinic Cheilitis) will be compiled in a table.

Conditions and MedDRA coding

Actinic Cheilitis

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥ 18 years
2. Newly diagnosed Actinic Cheilitis (clinically and by optical coherence tomography) or chronic Actinic Cheilitis at the time of registration (Clinic: atrophy of the lip (white coloration) or adhering , hyperkeratotic plaques or erosions; OCT: thickening of epidermis and increase in signal penetration and intact dermoepidermal junction zone)
3. Skin type I to III (Fitzpatrick scale)
4. Written informed consent after clarification

Exclusion criteria 22

1. Known genetic defect of the epidermal barrier (e.g. Netherton-Syndrome)
2. Signs of facial skin irritation (significant redness, dryness, burning sensation, stabbing sensation, pruritus) which cannot be attributed to Actinic Cheilitis
3. Simultaneous treatment with topical preparations (including cosmetics) or keratolytic substances (e.g. sulphur, salicylic acid, benzoyl peroxide, resorcine and chemical abrasives), soaps with peeling and strongly dehydrating effects, perfumes, citrus extracts, topical antibiotics, corticosteroids, retinoid or azalaic acid within 2 weeks before start of trial intervention (day 0)
4. Intensive natural or artificial UV light therapy (e.g. UVB, UVA, PUVA) within 4 weeks before start of trial intervention (day 0)
5. Intake of antibiotics or glucocorticosteroids within 4 weeks before start of trial intervention (day 0)
6. Intake of retinoids within 6 months before start of trial intervention (day 0)
7. Topical treatment of Actinic Cheilitis within 8 weeks before start of trial intervention (day 0)
8. Severe systemic concomitant diseases (as per investigator’s assessment) or any immunosuppressive treatment
9. Known severe renal- or hepatic diseases which need close surveillance and therapy
10. Local enteritis, ulcerative colitis or known antibiotic-associated colitis
11. Current or previous invasive squamous cell carcinoma of the respective lip intended for treatment
12. Active cancer disease
13. Known hypersensitivity towards the medicinal product under investigation or one of its components or towards medications of a similar chemical structure
14. Participation in another interventional clinical trial (up to 4 weeks before start of therapy)
15. Addiction or other concomitant diseases, which prevent the participant from understanding and comprehending the scope, nature and potential consequences of this clinical trial
16. Pregnant or lactating women
17. Male participants with partners of childbearing potential, not meeting at least one of the following criteria: Postmenopausal (12 months of amenorrhea by natural causes, or 6 months of amenorrhea in combination with a highly effective contraception method (Pearl Index <1%)); Post-surgery (6 weeks after bilateral ovariectomy, bilateral salpingectomy with or without a hysterectomy); Negative pregnancy test (urine, minimum sensitivity for Beta-HCG 25mIU/ml) and willingness to regularly and correctly use a highly effective contraceptive method (Pearl Index < 1 %) ((hormonal contraception (estrogen- gestagen combinations), hormonal contraception (progestogen preparations, oral, injected, implant), spiral (hormonal coil, copper IUD), confirmed partner’s vasectomy, abstinence from study incusion unitl final visit ))
18. Women of childbearing potential, except for women who meet at least one of the following criteria: Postmenopausal (12 months of amenorrhea by natural causes, or 6 months of amenorrhea in combination with a highly effective contraception method (Pearl Index <1%)); Post-surgery (6 weeks after bilateral ovariectomy, bilateral salpingectomy with or without a hysterectomy); Negative pregnancy test (urine, minimum required sensitivity for Beta-HCG 25mIU/ml Beta-HCG) and willingness to regularly and correctly use a highly effective contraceptive method (Pearl Index < 1 %) ((hormonal contraception (estrogen- gestagen combinations), hormonal contraception (progestogen preparations, oral, injected, implant), spiral (hormonal coil, copper IUD), confirmed sucessfull partner’s vasectomy, abstinence from study inclusion until the final visit))
19. Individuals who are unable to give consent
20. Individuals, who are dependent from the sponsor
21. Individuals, who are institutionalized or imprisoned by court order or other official institution
22. Any indication that the subject is unlikely to adhere to the protocol (e.g. lack of compliance)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete recovery rate (healing) of Actinic Cheilitis, 8 weeks after the application of Tirbanibulin for 5 days (visit 4, day 56). Complete recovery is defined as an affected area of 0 cm.

Secondary endpoints 6

1. Reduction of the affected area by means of the size of the affected lip area in cm² and the reduction of the affected area in % at day 56 compared to baseline (area in cm² at baseline, area in cm² at day 56, reduction of the area in %)
2. Study subject self-assessment (individual and total scores according to the visit schedule as well as the difference of the scores compared to baseline)
3. Local skin reaction score (individual and total scores as per visit schedule as well as the difference of the scores compared to baseline
4. Oral Health DLQI-Score (individual and total scores as per visit as well as the difference of the scores compared to baseline)
5. Frequency of AEs and SAEs during the duration of the trial (visit 4)
6. Discrepancies in diagnosing Actinic Cheilitis by means of optical coherence tomography, confocal laser scanning microscopy, line-field confocal optical coherence tomography, diagnostic confidence, imaging quality at baseline compared to the final visit.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Technische Universitat Dresden

Sponsor organisation

Technische Universitat Dresden

Address

Mommsenstrasse 11, Raecknitz/zschertnitz Raecknitz/zschertnitz

City

Dresden

Postcode

01069

Country

Germany

Scientific contact point

Organisation

Technische Universitat Dresden

Contact name

Dr. med. Roland Aschoff

Public contact point

Organisation

Technische Universitat Dresden

Contact name

Dr. med. Roland Aschoff

Locations

1 EU/EEA country · 1 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 2 files

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

Application history

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