Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%

NCT01926496 | Completed Phase 4 Results

• 2 other identifiers: LP0041-632012-003112-31
• Study Type: interventional
• Target: 485
• Locations: 3 countries
• Sites: 46

Brief Summary

The purpose of the study is to compare the risk of developing squamous skin cancer (SCC) or other types of cancer after treatment of AKs with ingenol mebutate gel or imiquimod cream. Subjects will be randomised to treatment with ingenol mebutate or imiquimod and will receive a second treatment cycle with the same treatment if the first treatment does not clear all AKs. Subjects will be followed over a period of three year (36 months) after first treatment

Conditions

Actinic Keratosis (AK)

Outcome Measures

Primary Outcomes (1)

• Incidence of SCC

  Cumulative incidence of SCC after treatment with ingenol mebutate gel and imiquimod cream.\> The primary response criterion is diagnosis of SCC (defined as invasive SCC i.e. excludes SCC in situ) in the treatment field across the 3-year trial period.\> Kaplan-Meier estimate based on time to SCC or censoring.

  3 years

Secondary Outcomes (4)

• Incidence of SCC and Other Neoplasia

  3 years

• Number of Participants With Complete Clearance of AK Lesions After Last Treatment

  8-16 weeks

• Number of Participants With Partial Clearance of AK Lesions

  8-16 weeks

• Number of Participants With Complete Clearance of AK Lesions at 12 Months

  1 year

Study Arms (2)

Ingenol Mebutate

EXPERIMENTAL

Arm A: Ingenol mebutate gel 0.015% applied daily for 3 consecutive days to the selected treatment area followed by 8 weeks' rest. Retreatment for another 3 consecutive days if the treatment field is not completely cleared of AKs at Week 8

Drug: Ingenol Mebutate Gel, 0.015%

Imiquimod

ACTIVE COMPARATOR

Arm B: Imiquimod 5% cream applied 3 days per week for 4 weeks to the selected treatment area followed by 4 weeks' rest. Retreatment for another 4 weeks if the treatment field is not completely cleared of AKs at Week 8

Drug: Imiquimod Cream, 5%

Interventions

Ingenol Mebutate Gel, 0.015% DRUG

Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.

Also known as: Picato®

Ingenol Mebutate

Imiquimod Cream, 5% DRUG

Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs

Also known as: Aldara®

Imiquimod

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF) prior to any trial-related procedures
• Subjects with 5 to 9 clinically typical, visible and discrete AKs within a contiguous 25 cm² treatment area on the face or scalp.
• Subject at least 18 years of age
• Female subjects must be of either:
• Non-childbearing potential, or,
• Childbearing potential, provided there is a confirmed negative urine pregnancy test
• Female subjects of childbearing potential must be willing to use highly effective methods of contraception (Pearl index \< 1%)

You may not qualify if:

• Location of the selected treatment area:
• on the periorbital skin
• on the perioral skin/around the nostrils
• within 5 cm of an incompletely healed wound
• within 10 cm of a suspected BCC or SCC or other neoplasia
• Selected treatment area lesions that have atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horn).
• History of SCC, BCC, malignant melanoma or other neoplasia in the selected treatment area.
• History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the trial medication in the selected treatment area
• Use of ingenol mebutate and/or imiquimod in and within 5 cm of the selected treatment area within 2 years prior to Screening (Visit 1)
• Organ transplant recipients
• Immunosuppressed subjects (for example HIV patients)
• Female subjects who are breastfeeding.
• Subjects who are institutionalised by court order or by the local authority
• In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state)

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (46)

CHU Angers - Service de Dermatologie

Angers, 49933, France

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

HOPITAL AVICENNE - Service de Dermatologie

Bobigny, 93009, France

Location

CHRU de Brest - Hôpital Morvan - Service de Dermatologie

Brest, 29609, France

Location

CHU Albert Michallon - Service de Dermatologie, Pôle Pluridisciplinaire de Médecine

Grenoble, 38043, France

Location

Hôpital Claude Huriez - CHRU de Lille - Clinique de Dermatologie

Lille, 59037, France

Location

Hôpital de la Timone - Service de Dermatologie Vénérologie

Marseille, 13385, France

Location

CHU de Nantes - Hôtel Dieu - Unité Fonctionnelle de Dermatologie Cancérologie

Nantes, 44093, France

Location

HOPITAL DE L ARCHET II - Service de Dermatologie-Vénérologie

Nice, 06202, France

Location

Hôpital Caremeau

Nîmes, 30029, France

Location

HOPITAL COCHIN TARNIER - Service de Dermatologie

Paris, 75006, France

Location

Hôpital Saint Louis - Service de Dermatologie

Paris, 75475, France

Location

CHU BORDEAUX - Hôpital Haut-Lévêque

Pessac, 33604, France

Location

CHU Poitiers - Service de Dermatologie

Poitiers, 86021, France

Location

C.H.U. de Saint-Etienne - Hôpital Nord

Saint-Etienne, 42055, France

Location

Hôpital d'instruction des Armées Bégin - Clinique Dermatologique

Saint-Mandé, 94160, France

Location

Hautarztpraxis Simon

Berlin, 10827, Germany

Location

Hauttumorzentrum Bochum Universitätsklinikum der Ruhr-Universität-Bochum

Bochum, 44791, Germany

Location

Praxis Streit Bucholz

Buchholz, 21244, Germany

Location

Dermatologisches Zentrum, Am Krankenhaus 1

Buxtehude, 21614, Germany

Location

Klinikum Dortmund - Hautklinik

Dortmund, 44137, Germany

Location

Mensingderma

Hamburg, 22391, Germany

Location

Universitätsklinikum Leipzig Klinik für Dermatologie, Venerologie und Allergologie

Leipzig, 04103, Germany

Location

Hautpraxis Dr. Ina Schulze

Markkleeberg, 04416, Germany

Location

Hauttumorzentrum Münster

Münster, 48149, Germany

Location

Klinik für Dermatologie und Allergologie, Klinikum Vest, Behandlungszentrum, Knappschaftskrankenhaus Recklinghausen,

Recklinghausen, 45657, Germany

Location

Universitätklinikum Regensburg

Regensburg, 93053, Germany

Location

Praxis Dr. Hoffmann

Witten, 58453, Germany

Location

Praxis Derma Hübinger

Wuppertal, 42105, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Ninewells Hospital

Dundee, Angus, United Kingdom

Location

Cumberland Infirmary

Carlisle, Cumbria, United Kingdom

Location

Heavitree Hospital

Exeter, Devon, United Kingdom

Location

Brighton General Hospital

Brighton, East Sussex, United Kingdom

Location

Manchester Royal Infirmary

Manchester, Greater Manchester, United Kingdom

Location

Monklands Hospital

Airdrie, Lanarkshire, United Kingdom

Location

Scunthorpe General Hospital

Scunthorpe, Lincolnshire, United Kingdom

Location

Royal Gwent Hospital

Newport, Monmouthshire, United Kingdom

Location

Harrogate District Hospital

Harrogate, North Yorkshire, United Kingdom

Location

Scarborough Hospital

Scarborough, North Yorkshire, United Kingdom

Location

Cannock Chase Hospital

Cannock, Staffordshire, United Kingdom

Location

East Surrey Hospital

Redhill, Surrey, United Kingdom

Location

Southlands Hospital

Shoreham-by-Sea, West Sussex, United Kingdom

Location

St Luke's Hospital

Bradford, West Yorkshire, United Kingdom

Location

Chapel Allerton Hospital

Leeds, West Yorkshire, United Kingdom

Location

Hull Royal Infirmary

Hull, United Kingdom

Location

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

3-ingenyl angelate; Imiquimod

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Disclosure
• Organization: LEO Pharma A/S

disclosure@leo-pharma.com

+45 44945888

Study Officials

• Rolf-Markus Szeimies, Prof.Dr.med.

  Klinik für Dermatologie und Allergologie

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: August 21, 2013
• Study Start: September 11, 2013
• Primary Completion: July 11, 2019
• Study Completion: July 11, 2019
• Last Updated: March 7, 2025
• Results First Posted: July 29, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (14); FR (16); GB (16)