5% KOH Solution vs. Placebo and Diclofenac Gel for the Treatment of Actinic Keratosis

Study Overview
=================
Brief Summary
-----------------
The KOHDIAK study is a prospective, three-armed, randomised, double-blind study to evaluate the efficacy and safety of the treatment of mild and moderate actinic keratosis with a 5% potassium hydroxide solution (Solcera, medical device) versus placebo and investigator-blinded comparison with 3% diclofenac gel (Solaraze, medicinal product). It is performed in accordance with both the laws in force for clinical trials with medical devices and those with medicinal products.

Official Title
-----------------
Prospective, Three-armed, Randomised, Double-blind Study to Evaluate the Efficacy and Safety of the Treatment of Mild and Moderate Actinic Keratosis With a 5% Potassium Hydroxide Solution (Solcera, Medical Device) Versus Placebo and Investigator-blinded Comparison With 3% Diclofenac Gel (Solaraze, Medicinal Product) (Regulated by the Laws for Both Medical Devices and Medicinal Products)

Conditions
-----------------
Actinic Keratosis

Intervention / Treatment
-----------------
* Device: Solcera
* Device: Placebo
* Drug: Solaraze


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years and < 90 years Actinic keratosis grade I (mild) or II (moderate) according to the definition by Olsen with palpable or clinically/dermatoscopically apparent keratosis Either lesions being well accessible/treatable by the patient or presence of a second person to do the daily applications Written informed consent by the patient Exclusion Criteria: Number of initial lesions to be treated ≥ 6 Overall size of the area to be treated > 25 cm2 Size (maximum diameter) of single lesion to be treated > 20 mm Lesions in close proximity to the eyes, eyelids, nostrils, mouth or mucosal tissue Need for topical treatment of cancerous area Presence of a relapsing, persistent, indurated, thickened, painful, bleeding, ulcerated and/or rapidly growing lesion Existing skin cancer (all forms of skin cancer incl. basal-cell carcinoma and squamous cell carcinoma) in the area to be treated in this study Dermal injuries, skin infection or exfoliative dermatitis in the area to be treated in this study Other skin diseases in the area to be treated in this study that affect the diagnostic assessment Pharmacological or physical local therapy of actinic keratosis (or application of the active ingredients used in the pharmacological therapy) in the area to be treated in this study during the last 4 weeks Primary or secondary immunodeficiency Treatment with interferons, interferon inducers, immunomodulators or systemic corticosteroids during the last 4 weeks Treatment with oral isotretinoin during the last 6 months Intracranial bleeding in the medical history or generally increased primary bleeding tendency Known intolerance/hypersensitivity to one of the ingredients of the investigational products, especially to diclofenac, parabens or benzyl alcohol as well as to NSAIDs, in particular acetylsalicylic acid Pregnancy and lactation Women of child-bearing potential either wishing to become pregnant or without effective contraception Other serious diseases, which are (according to the investigator's assessment) in conflict with the study participation (i.a. also in view of risk factors for a severe course of a potential COVID-19 disease in case of a SARS-CoV-2 infection) Obvious unreliability or lack of cooperation Known addiction to alcohol, medicinal products or drugs Dependency on the sponsor or an investigator Participation in a clinical trial during the last 30 days Previous participation in the present clinical trial Participation of a family member (in the same household) in the present clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solcera<br> | Device: Solcera<br>* Twice daily application for a duration of 4 weeks followed by another 4 weeks without treatment (up to 2 potential repetitions of this 8-week cycle)<br>|
| Placebo Comparator: Placebo<br> | Device: Placebo<br>* Twice daily application for a duration of 4 weeks followed by another 4 weeks without treatment (up to 2 potential repetitions of this 8-week cycle)<br>|
| Active Comparator: Solaraze<br> | Drug: Solaraze<br>* Twice daily application for a duration of 60 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success | Treatment success, defined as complete, dermatoscopically confirmed remission of all initial actinic keratosis (AK) lesions identified at treatment start that have been treated with the investigational product (Complete Clearance) | At the control visit at the end of treatment (EOT, i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success | Treatment success, defined as complete, dermatoscopically confirmed remission of all initial AK lesions identified at treatment start that have been treated with the investigational product (Complete Clearance) | For Solaraze at day 90 | 
| (Healing) status of AK lesions | (Healing) status of AK lesions (number of proliferating lesions, unchanged/stable lesions, lesions being in remission or showing partial remission, lesions with complete remission, and relapses; overall and grouped by localisation and size (0-5 mm, 6-10 mm, 11-15 mm, 16-20 mm)); analysed for a) initial AK lesions identified at treatment start that have been treated with the investigational product, b) new AK lesions appearing in the treated area after treatment start, c) all AK lesions (i.e. a) + b)) | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Overall number of AK lesions | Overall number of initial AK lesions identified at treatment start that have been treated with the investigational product (i.e. without AK lesions with complete remission) | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Mean size of AK lesions | Mean size of initial AK lesions identified at treatment start that have been treated with the investigational product (lesion size determined by largest diameter) | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Treatment success | Treatment success (complete, dermatoscopically confirmed remission of lesions) analysed for a) initial AK lesions identified at treatment start that have been treated with the investigational product, b) new AK lesions appearing in the treated area after treatment start, c) all AK lesions (i.e. a) + b)) | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Partial clearance | Number of patients with partial clearance (i.e. all patients with at least 75% of the initial AK lesions identified at treatment start being assessed with complete remission) | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Reduction of AK lesion number | Reduction of AK lesion number per patient (in % compared to the number of initial AK lesions identified at treatment start) analysed for initial AK lesions identified at treatment start that have been treated with the investigational product | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Clinical response | Clinical response, i.e. the number of patients with at least one AK lesion being assessed with complete remission | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Lesion-based treatment success (without consideration of relapses) | Number of initial AK lesions identified at treatment start that have been treated with the investigational product, which showed complete remission at least once between treatment start and EOT | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Lesion-based treatment success (with consideration of relapses) | Number of initial AK lesions identified at treatment start that have been treated with the investigational product, which showed complete remission at the respectively analysed visit | At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks) | 
| Patients with relapse | Number of patients with at least one initial AK lesion being assessed as relapse after previous Complete Clearance (definition see above), analysed for the time period between treatment start and the follow-up visit after 24 weeks and analysed in reference to a) the number of all patients and b) the number of those patients with previous Complete Clearance | Analysed at the follow-up visit 24 weeks after treatment start for the time period between treatment start and the follow-up visit | 
| Lesions with relapse | Number of initial AK lesions being assessed as relapse, analysed for the time period between treatment start and the follow-up visit after 24 weeks and analysed in reference to a) the number of all initial lesions and b) the number of those initial lesions with previous complete remission | Analysed at the follow-up visit 24 weeks after treatment start for the time period between treatment start and the follow-up visit | 
| Efficacy assessment by physician | Assessment of the efficacy (scale based on school grades 1-6) by the treating physician | At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start | 
| Efficacy assessment by patient | Assessment of the efficacy (scale based on school grades 1-6) by the patient | At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start | 
| Tolerability assessment by physician | Assessment of the tolerability (scale based on school grades 1-6) by the treating physician | At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start | 
| Tolerability assessment by patient | Assessment of the tolerability (scale based on school grades 1-6) by the patient | At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start | 
| Overall assessment by physician | Overall assessment (scale based on school grades 1-6) by the treating physician | At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start | 
| Overall assessment by patient | Overall assessment (scale based on school grades 1-6) by the patient | At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start | 
| Adverse Events, Serious Adverse Events, Adverse Reactions | Number and frequency of Adverse Events, Serious Adverse Events and Adverse Reactions | In the time period between start of treatment and the follow-up visit (24 weeks after treatment start) | 
| Dropouts | All dropouts (incl. specification of reason and date) | In the time period between start of treatment and the follow-up visit (24 weeks after treatment start) | 
| Compliance | Compliance of the patients with the application schedule of the respective investigational product (based on entries in the patient diary and only overruled by the weight of returned investigational products in case of clear discrepancies) | Analysed for the respective time period of scheduled product application, i.e. Day 0 until Day 60 for Solaraze and 1-3x 28 days (depeding on number of cycles) for Solcera/Placebo | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Actinic Keratosis, Solcera, Prospective, Multicentric, Monitored, Efficacy, Safety, Potassium Hydroxide, Randomized, Double-Blind