Actinic Keratosis (AK)Phase 4NCT01926496

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

A Phase 4 study testing Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5% in people with Actinic Keratosis (AK), run by LEO Pharma at 46 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Actinic Keratosis (AK)
What is being tested?: Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 485 participants
Where: 46 sitesin 3 countries
Study dates: 11 Sep 2013to 11 Jul 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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%)

Who cannot join

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).

Show all 14Show fewer

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)

Trial locations and contacts

46 sites in 3 countries.

Country

City, postcode or hospital

46 sites in 3 countries

France16 sites

CHU Angers - Service de Dermatologie
Angers, 49933
CHU Besançon - Hôpital Jean Minjoz
Besançon, 25030
HOPITAL AVICENNE - Service de Dermatologie
Bobigny, 93009
CHRU de Brest - Hôpital Morvan - Service de Dermatologie
Brest, 29609
CHU Albert Michallon - Service de Dermatologie, Pôle Pluridisciplinaire de Médecine
Grenoble, 38043
Hôpital Claude Huriez - CHRU de Lille - Clinique de Dermatologie
Lille, 59037
Hôpital de la Timone - Service de Dermatologie Vénérologie
Marseille, 13385
CHU de Nantes - Hôtel Dieu - Unité Fonctionnelle de Dermatologie Cancérologie
Nantes, 44093
HOPITAL DE L ARCHET II - Service de Dermatologie-Vénérologie
Nice, 06202
Hôpital Caremeau
Nîmes, 30029
HOPITAL COCHIN TARNIER - Service de Dermatologie
Paris, 75006
Hôpital Saint Louis - Service de Dermatologie
Paris, 75475
CHU BORDEAUX - Hôpital Haut-Lévêque
Pessac, 33604
CHU Poitiers - Service de Dermatologie
Poitiers, 86021
C.H.U. de Saint-Etienne - Hôpital Nord
Saint-Etienne, 42055
Hôpital d'instruction des Armées Bégin - Clinique Dermatologique
Saint-Mandé, 94160

Other trials in France

United Kingdom16 sites

Monklands Hospital
Airdrie, Lanarkshire
St Luke's Hospital
Bradford, West Yorkshire
Brighton General Hospital
Brighton, East Sussex
Cannock Chase Hospital
Cannock, Staffordshire
Cumberland Infirmary
Carlisle, Cumbria
Ninewells Hospital
Dundee, Angus
Heavitree Hospital
Exeter, Devon
Harrogate District Hospital
Harrogate, North Yorkshire
Hull Royal Infirmary
Hull
Chapel Allerton Hospital
Leeds, West Yorkshire
Manchester Royal Infirmary
Manchester, Greater Manchester
Royal Gwent Hospital
Newport, Monmouthshire
East Surrey Hospital
Redhill, Surrey
Scarborough Hospital
Scarborough, North Yorkshire
Scunthorpe General Hospital
Scunthorpe, Lincolnshire
Southlands Hospital
Shoreham-by-Sea, West Sussex

Other trials in United Kingdom

Germany14 sites

Hautarztpraxis Simon
Berlin, 10827
Hauttumorzentrum Bochum Universitätsklinikum der Ruhr-Universität-Bochum
Bochum, 44791
Praxis Streit Bucholz
Buchholz, 21244
Dermatologisches Zentrum, Am Krankenhaus 1
Buxtehude, 21614
Klinikum Dortmund - Hautklinik
Dortmund, 44137
Mensingderma
Hamburg, 22391
Universitätsklinikum Leipzig Klinik für Dermatologie, Venerologie und Allergologie
Leipzig, 04103
Hautpraxis Dr. Ina Schulze
Markkleeberg, 04416
Hauttumorzentrum Münster
Münster, 48149
Klinik für Dermatologie und Allergologie, Klinikum Vest, Behandlungszentrum, Knappschaftskrankenhaus Recklinghausen,
Recklinghausen, 45657
Universitätklinikum Regensburg
Regensburg, 93053
Praxis Dr. Hoffmann
Witten, 58453
Praxis Derma Hübinger
Wuppertal, 42105
Universitätsklinikum Würzburg
Würzburg, 97080

Other trials in Germany

About this study

Official title: A Phase 4 Trial Comparing the Cumulative Incidence of SCC After Treatment With Ingenol Mebutate and Imiquimod for Multiple Actinic Keratoses on Face and Scalp. A Multi-centre, Randomised, Two-arm, Open Label, Active-controlled, Parallel Group, 36-month Trial

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)
Being tested: Ingenol Mebutate Gel, 0.015%, Imiquimod Cream, 5%
Medical subject headings: Keratosis, Actinic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ingenol Mebutate Gel, 0.015%Drug
Also called Picato®
Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.
Imiquimod Cream, 5%Drug
Also called Aldara®
Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs

Study groups in NCT01926496
Study group	Role	What they receive
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 Receives: 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 Receives: Drug: Imiquimod Cream, 5%

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 3 years

Secondary outcomes (4)

Incidence of SCC and Other Neoplasia
Cumulative incidence of SCC and other neoplasia after treatment with ingenol mebutate gel and imiquimod cream.> The secondary response criterion is diagnosis of SCC and other neoplasia in the treatment field across the 3-year trial period.> Kaplan-Meier estimate based on time to SCC and other neoplasia, or censoring.
Measured: 3 years
Number of Participants With Complete Clearance of AK Lesions After Last Treatment
To compare the complete clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)
Measured: 8-16 weeks
Number of Participants With Partial Clearance of AK Lesions
To compare the partial (at least 75%) clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)
Measured: 8-16 weeks
Number of Participants With Complete Clearance of AK Lesions at 12 Months
To compare the complete clearance of AK lesions at 12 months, defined as no AK lesions in the selected treatment area at any time from the last treatment cycle at Week 8 or 16 through to Month 12.
Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 201311 Jul 2019

First posted21 Aug 2013 (estimated)
Study start11 Sep 2013
Primary completion11 Jul 2019
Study completion11 Jul 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Actinic Keratosis (AK)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 485 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01926496
Sponsor's protocol ID: LP0041-63
Other IDs: 2012-003112-31
Status last verified: Aug 2020
First submitted: 19 Aug 2013
Last updated: 7 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Actinic Keratosis (AK) trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 4 Trial Comparing the Cumulative Incidence of SCC After Treatment With Ingenol Mebutate and Imiquimod for Multiple Actinic Keratoses on Face and Scalp. A Multi-centre, Randomised, Two-arm, Open Label, Active-controlled, Parallel Group, 36-month Trial
ClinicalTrials.gov ID: NCT01926496
Acronym / sponsor ID: LP0041-63
Conditions: Actinic Keratosis (AK)
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 485 participants (actual)
Lead sponsor: LEO PharmaIndustry (pharma, biotech, devices)
Study start: 11 Sep 2013 (actual)
Primary completion: 11 Jul 2019 (actual)
Study completion: 11 Jul 2019 (actual)
First posted: 21 Aug 2013 (estimated)
Results: Posted 29 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Ingenol Mebutate	Experimental	Drug: Ingenol Mebutate Gel, 0.015%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
Imiquimod	Active comparator	Drug: Imiquimod Cream, 5%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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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:
Female subjects of childbearing potential must be willing to use highly effective methods of contraception (Pearl index < 1%)

Key exclusion criteria (14 listed)

Location of the selected treatment area:
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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ingenol Mebutate Gel, 0.015%Also: Picato®Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.	Drug	Ingenol Mebutate
Imiquimod Cream, 5%Also: Aldara®Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs	Drug	Imiquimod

Primary outcome

Incidence of SCC
Time frame: 3 years
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.

4 secondary outcomes

Incidence of SCC and Other Neoplasia
Time frame: 3 years
Number of Participants With Complete Clearance of AK Lesions After Last Treatment
Time frame: 8-16 weeks
Number of Participants With Partial Clearance of AK Lesions
Time frame: 8-16 weeks
Number of Participants With Complete Clearance of AK Lesions at 12 Months
Time frame: 1 year

Results and safety

Results posted to the registry on 29 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ingenol Mebutate	240	203
Imiquimod	245	197

Primary outcome: Incidence of SCC

Time frame: 3 years. Number (95% Confidence Interval). Unit: percentage of subjects

Measure	Ingenol Mebutate n = 240	Imiquimod n = 244
Value	3.1 (1.4 to 6.0)	0.4 (0.0 to 2.2)

Population analysed: Safety analysis set: all treated subjects

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Day 1 and up to 3 years.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ingenol Mebutate Until Week 20	21 of 240 (8.8%)	67 of 240 (27.9%)	0 of 240
Imiquimod Until Week 20	14 of 244 (5.7%)	70 of 244 (28.7%)	1 of 244
Ingenol Mebutate After Week 20	11 of 240 (4.6%)	51 of 240 (21.3%)	8 of 240
Imiquimod After Week 20	2 of 244 (0.8%)	50 of 244 (20.5%)	5 of 244

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Actinic Keratosis (AK)

RecruitingPhase 3
Study of Reformulated Levulan Kerastick Plus PDT for Actinic Keratosis on Upper Extremities
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RecruitingPhase 3
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Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rolf-Markus Szeimies, Prof.Dr.med. principal investigator

Klinik für Dermatologie und Allergologie

46 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5% in people with Actinic Keratosis (AK), run by LEO Pharma at 46 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in France, United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of SCC (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01926496.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2025.