Actinic KeratosisPhase 1/2NCT01820260
Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis
A Phase 1/2 study testing Ingenol mebutate gel in people with Actinic Keratosis, run by LEO Pharma at 1 site in United States.
Trial summary
To identify the Maximum Tolerated Dose levels of ingenol mebutate gel after once daily treatment for 2 or 3 consecutive days and to evaluate efficacy of ingenol mebutate gel in different doses after once daily treatment for 2 or 3 consecutive days compared to vehicle gel Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Actinic Keratosis
- What is being tested?
- Ingenol mebutate gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 395 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2013to Aug 2014
- Phase
- Phase 1/2
- 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
- Subjects must be competent to understand the nature of the trial and provide informed consent
- Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face, the balding scalp (the balding part of the scalp should be at least 25 cm2) or a contiguous area of approximately 250 cm2 on the chest
- Subject at least 18 years of age
- Female subjects must be of either:
- Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or,
- Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment, to rule out pregnancy
- Female subjects of childbearing potential1 must be willing to use effective contraception at trial entry and until completion
Who cannot join
- Location of the treatment area (full face, full balding scalp or chest)
- within 5 cm of an incompletely healed wound,
- within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC
- Prior treatment with ingenol mebutate gel within the treatment area
- Lesions in the treatment areas that have:
- atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or,
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- recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions
- History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
- Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
- Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety and efficacy during the course of the trial, as determined by the investigator's clinical judgment
- Any abnormal laboratory tests that are medically significant and would impact the safety of the subjects or the interpretation of the trial results, as determined by the investigator's judgment
- Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in Prohibited Therapies or Medications
- Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel
- Presence of acute sunburn within the treatment areas
- Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.
- Subjects previously assigned to treatment in Part 1 or rand
- Female subjects who are breastfeeding.
- 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
1 site in 1 country.
United States1 site
Laser & Skin Surgery Center of Inidana
Carmel, Indiana, 46032
About this study
Official title: Safety and Efficacy of Escalating Doses of Ingenol Mebutate Once Daily for Two or Three Consecutive Days When Used on Full Face, Full Balding Scalp or Approximately 250 cm2 on the Chest in Subjects With Actinic Keratosis
To identify the Maximum Tolerated Dose levels of ingenol mebutate gel after once daily treatment for 2 or 3 consecutive days and to evaluate efficacy of ingenol mebutate gel in different doses after once daily treatment for 2 or 3 consecutive days compared to vehicle gel
- Conditions
- Actinic Keratosis
- Being tested
- Ingenol mebutate gel, placebo
- 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 gelDrug
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Part 1A: Ingenol mebutate gel 0.005% | Experimental | Open-label, dose escalation, 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 2: Ingenol mebutate gel 0.018% for 3 days treatment | Active comparator | Randomized, 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 2: Ingenol mebutate gel 0.018% for 2 days treatment | Active comparator | Randomized 2 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 2: Ingenol mebutate gel 0.027% for 3 days treatment | Active comparator | Randomized 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 2: Ingenol mebutate gel 0.027% for 2 days treatment | Active comparator | Randomized 2 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 2: Placebo for 3 days treatment | Placebo comparator | Randomized 3 days treatment Receives: Drug: placebo |
| Part 2: Placebo for 2 days treatment | Placebo comparator | Randomized 2 days treatment Receives: Drug: placebo |
| Part 1A: Ingenol mebutate gel 0.008% | Experimental | Open-label, dose escalation, 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 1A: Ingenol mebutate gel 0.012% | Experimental | Open-label, dose escalation, 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 1A: Ingenol mebutate gel 0.027% | Experimental | Open-label, dose escalation, 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 1A: Ingenol mebutate gel 0.04% | Experimental | Open-label, dose escalation, 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 1B: Ingenol mebutate gel 0.06% | Experimental | Open-label, dose escalation, 2 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 1A: Ingenol mebutate gel 0.018% | Experimental | Open-label, dose escalation, 3 days treatment Receives: Drug: Ingenol mebutate gel |
| Part 1B: Ingenol mebutate gel 0.04% | Experimental | Open-label, dose escalation, 2 days treatment Receives: Drug: Ingenol mebutate gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days
Dose tolerability was measures looking at the composite score of Local Skin Responses (LSR). The MTD was defined as the highest dose level with less than 4 subjects out of 12 experiencing dose limiting toxicity (DLT).
DLT was defined as one or more of the following three local skin LSRs:
- Crusting Grade 4
- Erosion/Ulceration Grade 4
- Vesiculation/Pustulation Grade 4 or two or more of the following five LSRs:
- Erythema Grade 4
- Crusting Grade 3
- Swelling Grade 4
- Erosion/Ulceration Grade 3
- Vesiculation/Pustulation Grade 3
The grading is a scale of 1 to 4 (highest grade).
Measured: 8 days after initial treatment
Part 2: Number of Subjects With Complete Clearance of AKs
Number of subjects with complete clearance of Actinic Keratosis lesions (AKs) at week 8 after 2 or 3 consecutive days of treatment with ingenol mebutate gel on the full face, full balding scalp or approximately 250 cm² on the chest
Measured: 8 weeks
Secondary outcomes (2)
Part 2: Reduction in AK Count
Reduction in actinic keratosis lesion count from baseline to week 8 (percentage, adjusted for anatomical location and pooled site)
Measured: From baseline to Week 8
Part 2: Number of Subjects With Partial Clearance of AKs
Partial clearance of AKs at Week 8, defined as at least 75% reduction from baseline in the number of clinically visible AKs
Measured: Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2013 (estimated)
- Study startApr 2013
- Primary completionAug 2014
- Study completionAug 2014
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 KeratosisStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Part 1 was an open-label, dose escalation. Part 2 was a randomised, double-blind, parallel group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 395 participants (actual)
Sponsor and investigators
- Lead sponsor
- LEO Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- C. William Hanke, MD, Principal investigator, Laser & Skin Surgery Center of Indiana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01820260
- Sponsor's protocol ID
- LP0105-1012
- Status last verified
- May 2021
- First submitted
- 25 Mar 2013
- Last updated
- 13 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Escalating Doses of Ingenol Mebutate Once Daily for Two or Three Consecutive Days When Used on Full Face, Full Balding Scalp or Approximately 250 cm2 on the Chest in Subjects With Actinic Keratosis
- ClinicalTrials.gov ID
- NCT01820260
- Acronym / sponsor ID
- LP0105-1012
- Conditions
- Actinic Keratosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 395 participants (actual)
- Lead sponsor
- LEO PharmaIndustry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 28 Mar 2013 (estimated)
- Results
- Posted 25 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To identify the Maximum Tolerated Dose levels of ingenol mebutate gel after once daily treatment for 2 or 3 consecutive days and to evaluate efficacy of ingenol mebutate gel in different doses after once daily treatment for 2 or 3 consecutive days compared to vehicle gel
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 14
- Model description
- Part 1 was an open-label, dose escalation. Part 2 was a randomised, double-blind, parallel group
| Arm | Type | Receives |
|---|---|---|
| Part 1A: Ingenol mebutate gel 0.005% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 3 days treatment |
| Part 2: Ingenol mebutate gel 0.018% for 3 days treatment | Active comparator | Drug: Ingenol mebutate gelRandomized, 3 days treatment |
| Part 2: Ingenol mebutate gel 0.018% for 2 days treatment | Active comparator | Drug: Ingenol mebutate gelRandomized 2 days treatment |
| Part 2: Ingenol mebutate gel 0.027% for 3 days treatment | Active comparator | Drug: Ingenol mebutate gelRandomized 3 days treatment |
| Part 2: Ingenol mebutate gel 0.027% for 2 days treatment | Active comparator | Drug: Ingenol mebutate gelRandomized 2 days treatment |
| Part 2: Placebo for 3 days treatment | Placebo comparator | Drug: placeboRandomized 3 days treatment |
| Part 2: Placebo for 2 days treatment | Placebo comparator | Drug: placeboRandomized 2 days treatment |
| Part 1A: Ingenol mebutate gel 0.008% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 3 days treatment |
| Part 1A: Ingenol mebutate gel 0.012% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 3 days treatment |
| Part 1A: Ingenol mebutate gel 0.027% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 3 days treatment |
| Part 1A: Ingenol mebutate gel 0.04% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 3 days treatment |
| Part 1B: Ingenol mebutate gel 0.06% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 2 days treatment |
| Part 1A: Ingenol mebutate gel 0.018% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 3 days treatment |
| Part 1B: Ingenol mebutate gel 0.04% | Experimental | Drug: Ingenol mebutate gelOpen-label, dose escalation, 2 days treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must be competent to understand the nature of the trial and provide informed consent
- Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face, the balding scalp (the balding part of the scalp should be at least 25 cm2) or a contiguous area of approximately 250 cm2 on the chest
- Subject at least 18 years of age
- Female subjects must be of either:
- Female subjects of childbearing potential1 must be willing to use effective contraception at trial entry and until completion
Key exclusion criteria (18 listed)
- Location of the treatment area (full face, full balding scalp or chest)
- Prior treatment with ingenol mebutate gel within the treatment area
- Lesions in the treatment areas that have:
- History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
- Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
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 | Drug | Part 1A: Ingenol mebutate gel 0.005%, Part 1A: Ingenol mebutate gel 0.008%, Part 1A: Ingenol mebutate gel 0.012%, Part 1A: Ingenol mebutate gel 0.018%, Part 1A: Ingenol mebutate gel 0.027%, Part 1A: Ingenol mebutate gel 0.04%, Part 1B: Ingenol mebutate gel 0.04%, Part 1B: Ingenol mebutate gel 0.06%, Part 2: Ingenol mebutate gel 0.018% for 2 days treatment, Part 2: Ingenol mebutate gel 0.018% for 3 days treatment, Part 2: Ingenol mebutate gel 0.027% for 2 days treatment, Part 2: Ingenol mebutate gel 0.027% for 3 days treatment |
| placebo | Drug | Part 2: Placebo for 2 days treatment, Part 2: Placebo for 3 days treatment |
Primary outcome
Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days
Time frame: 8 days after initial treatment
Dose tolerability was measures looking at the composite score of Local Skin Responses (LSR). The MTD was defined as the highest dose level with less than 4 subjects out of 12 experiencing dose limiting toxicity (DLT). DLT was defined as one or more of the following three local skin LSRs: * Crusting Grade 4 * Erosion/Ulceration Grade 4 * Vesiculation/Pustulation Grade 4 or two or more of the following five LSRs: * Erythema Grade 4 * Crusting Grade 3 * Swelling Grade 4 * Erosion/Ulceration Grade 3 * Vesiculation/Pustulation Grade 3 The grading is a scale of 1 to 4 (highest grade).
Part 2: Number of Subjects With Complete Clearance of AKs
Time frame: 8 weeks
Number of subjects with complete clearance of Actinic Keratosis lesions (AKs) at week 8 after 2 or 3 consecutive days of treatment with ingenol mebutate gel on the full face, full balding scalp or approximately 250 cm² on the chest
2 secondary outcomes
Part 2: Reduction in AK Count
Time frame: From baseline to Week 8
Part 2: Number of Subjects With Partial Clearance of AKs
Time frame: Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
C. William Hanke, MD principal investigator
Laser & Skin Surgery Center of Indiana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ingenol mebutate gel in people with Actinic Keratosis, run by LEO Pharma at 1 site in United States.
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 18 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 13 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 1 site in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 25 May 2021). 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?
Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days (time frame: 8 days after initial treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2025.