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

• Sponsor: Infectopharm Arzneimittel GmbH (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04552327
• Collaborator: Gesellschaft für Therapieforschung mbH (Industry)
• Enrollment: 630
• Locations: 18
• Arms: 3
• Anticipated Duration (Months): 34.6
• Patients Per Site: 35
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratosis	Device: Solcera; Device: Placebo; Drug: Solaraze	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 630 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Oct 14, 2020
• Anticipated Primary Completion Date: Sep 1, 2023
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Solcera	Device: Solcera; 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)
Placebo Comparator: Placebo	Device: Placebo; 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)
Active Comparator: Solaraze	Drug: Solaraze; Twice daily application for a duration of 60 days

Outcome Measures

Primary Outcome Measures

1. Treatment success [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)]

   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")

Secondary Outcome Measures

1. Treatment success [For Solaraze at day 90]

   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")

2. (Healing) status of AK lesions [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)]

   (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))

3. Overall number of AK lesions [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 initial AK lesions identified at treatment start that have been treated with the investigational product (i.e. without AK lesions with complete remission)

4. Mean size of AK lesions [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 initial AK lesions identified at treatment start that have been treated with the investigational product (lesion size determined by largest diameter)

5. Treatment success [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 (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))

6. Partial clearance [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)]

   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")

7. Reduction of AK lesion number [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 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

8. Clinical response [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, i.e. the number of patients with at least one AK lesion being assessed with "complete remission"

9. Lesion-based treatment success (without consideration of relapses) [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)]

   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

10. Lesion-based treatment success (with consideration of relapses) [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)]

    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

11. Patients with relapse [Analysed at the follow-up visit 24 weeks after treatment start for the time period between treatment start and the follow-up visit]

    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"

12. Lesions with relapse [Analysed at the follow-up visit 24 weeks after treatment start for the time period between treatment start and the follow-up visit]

    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"

13. Efficacy assessment by 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]

    Assessment of the efficacy (scale based on school grades 1-6) by the treating physician

14. Efficacy assessment by 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]

    Assessment of the efficacy (scale based on school grades 1-6) by the patient

15. Tolerability assessment by 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]

    Assessment of the tolerability (scale based on school grades 1-6) by the treating physician

16. Tolerability assessment by 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]

    Assessment of the tolerability (scale based on school grades 1-6) by the patient

17. Overall assessment by 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 (scale based on school grades 1-6) by the treating physician

18. Overall assessment by 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 (scale based on school grades 1-6) by the patient

19. Adverse Events, Serious Adverse Events, Adverse Reactions [In the time period between start of treatment and the follow-up visit (24 weeks after treatment start)]

    Number and frequency of Adverse Events, Serious Adverse Events and Adverse Reactions

20. Dropouts [In the time period between start of treatment and the follow-up visit (24 weeks after treatment start)]

    All dropouts (incl. specification of reason and date)

21. Compliance [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]

    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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hautmedizin Bad Soden	Bad Soden		Germany	65812
2	MVZ - Dermatologisches Zentrum Bonn GmbH	Bonn		Germany	53111
3	Proderma Studienzentrum	Dülmen		Germany
4	Hautarztpraxis Falkensee	Falkensee		Germany	14612
5	Hautzentrum Südbaden	Freiburg		Germany
6	Hautarztzentrum Hamm	Hamm		Germany
7	Praxis Dres. Med. Markus Kaspari und Florian Schenk	Hannover		Germany	30159
8	Durani Cosmetics GmbH	Heidelberg		Germany
9	Hautarztpraxis Ibbenbüren	Ibbenbüren		Germany
10	Hautzentrum Köln	Köln		Germany	50996
11	Praxis Dres. K.-H. Vehring/U. Amann	Lingen		Germany	49809
12	Zentderma GBR	Mönchengladbach		Germany	41061
13	Haut- und Laserzentrum	Potsdam		Germany
14	Hautarztpraxis Asefi/Sadjadi	Simmern		Germany
15	Hautarztpraxis Leitz und Kollegen	Stuttgart		Germany
16	Hautarztpraxis Vilshofen	Vilshofen		Germany	94474
17	Centroderm GmbH	Wuppertal		Germany	42287
18	Hautzentrum Wuppertal	Wuppertal		Germany	42349

Sponsors and Collaborators

• Infectopharm Arzneimittel GmbH
• Gesellschaft für Therapieforschung mbH

Investigators

• Study Director: Uwe Reinhold, Prof., MVZ - Dermatologisches Zentrum Bonn GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Infectopharm Arzneimittel GmbH
• ClinicalTrials.gov Identifier: NCT04552327
• Other Study ID Numbers: KOHDIAK
• First Posted: Sep 17, 2020
• Last Update Posted: Nov 2, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Infectopharm Arzneimittel GmbH: Actinic Keratosis; Solcera; Prospective; Multicentric; Monitored; Efficacy; Safety; Potassium Hydroxide; Randomized; Double-Blind
• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis; Diclofenac

Study Results

No Results Posted as of Nov 2, 2021