Actinic Keratosis
Conditions
Keywords
Actinic Keratosis, Ingenol mebutate gel
Brief summary
The purpose of this trial is to evaluate the safety of a simultaneous treatment regimen compared to a sequential treatment regimen when two separate areas with AKs (one located on face/scalp and the other located on trunk/ extremities) are treated with ingenol mebutate gel
Interventions
DRUGIngenol mebutate gel 0.05 %
Ingenol mebutate gel 0.05 % (Picato®) on trunk/extremities either applied simultaneously or sequentially
DRUGIngenol mebutate gel 0.015 %
Ingenol mebutate gel 0.015 % (Picato®) on face/scalp either applied simultaneously or sequentially
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must provide informed consent * Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous 25 cm2 treatment area on face or scalp * Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous 25 cm2 treatment area on trunk or extremities * Subjects at least 18 years of age * Female subjects must be of either: 1. Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or, 2. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment, to rule out pregnancy. * Female subjects of childbearing potential must be willing to use effective contraception at trial entry and until completion.
Exclusion criteria
* Location of the selected treatment areas: * on the periorbital skin * 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 on face/scalp and on trunk/extremities * Lesions in the selected treatment areas that have: * atypical clinical appearance (and/or, * recalcitrant disease * History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication * Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the selected 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. * Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. * Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel * Presence of sunburn within the selected treatment areas * Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial * Subjects previously randomised in the trial * Female subjects who are breastfeeding * In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol Prohibited Therapies and/or Medications within 2 weeks prior to Visit 1: * Cosmetic or therapeutic procedures within 2 cm of the selected treatment areas * Use of topical keratolytic therapeutic products within 2 cm of the selected treatment areas * Use of topical medicated creams, ointments, lotions, gels, foams or sprays including topical steroids : within 2 cm of the selected treatment areas; artificial tanners: within 5 cm of the selected treatment areas Prohibited Therapies and/or Medications: within 4 weeks prior to Visit 1: * Treatment with immunomodulators, cytotoxic drugs or interferon/interferon inducers * Treatment with systemic medications that suppress the immune system * Treatment/therapy with ultraviolet light A (UVA) or ultraviolet light B (UVB) Prohibited Therapies and/or Medications within 8 weeks prior to Visit 1: \- Treatment with 5-fluorouracil (5-FU), imiquimod, topical diclofenac sodium, or photodynamic therapy within 2 cm of the selected treatment areas. Prohibited Therapies and/or Medications within 6 months prior to Visit 1: \- Use of systemic retinoids or biologic/monoclonal antibody therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Local Skin Reaction (LSR) Score 3 Days After Treatment of Each Selected Treatment Area | 3 days after treatment of each selected treatment area | Composite Local Skin Reaction (LSR) score 3 days after treatment of each selected treatment area in both treatment groups (simultaneous or sequential). The composite LSR score (0 to 24), reflecting the sum of the individual LSR grades (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration, grade 0 to 4), was calculated for each selected treatment area at each visit.The composite LSR score ranges from 0 (best possible outcome) to 24 (worst possible outcome). Both affected areas were calculated together Per Arm. Each subject could contribute with up to 2 values (1 for each treated area). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 8 weeks after treatment | Partial clearance of Actinic Keratosis lesions (AKs) defined as 75% or greater reduction in Actinic Keratosis lesions (AKs) from start of treatment to 8 weeks after treatment, was analysed in each separate treatment area and presented by treatment regimen given as percentage of participatns with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together Per Arm (e.g. averaged). |
| Percent Reduction in Number of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 8 weeks after treatment | Percent reduction in number of Actinic Keratosis lesions (AKs) analysed for each separate treatment area and presented by treatment regimen. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together Per Arm (e.g. averaged). |
| Effectiveness Satisfaction Questionnaire for Medication (TSQM) | 8 weeks | Effectiveness TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived effectiveness of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome). |
| Complete Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 8 weeks after treatment | Complete clearance of Actinic Keratosis lesions (AKs) analysed in each separate treatment area and presented by treatment regimen given as percentage of participants with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together Per Arm (e.g. averaged). |
| Global Satisfaction TSQM | 8 weeks | Global Satisfaction TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived overall satisfaction with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome). |
| Convenience TSQM | 8 weeks | Convenience TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived convenience with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome). |
| Side Effects TSQM | 8 weeks | Side Effects TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived side effects of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome). |
Countries
Italy
Participant flow
Pre-assignment details
In the clinical study protocol 200 subjects were planned to be enrolled and 199 subjects were actually enrolled and randomised.
Participants by arm
| Arm | Count |
|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment Ingenol mebutate gel 0.05 %: Ingenol mebutate gel 0.05 % (Picato®) on trunk/extremities applied simultaneously
Ingenol mebutate gel 0.015 %: Ingenol mebutate gel 0.015 % (Picato®) on face/scalp applied simultaneously | 101 |
| Ingenol Mebutate Gel Sequential Treatment Ingenol mebutate gel 0.05 %: Ingenol mebutate gel 0.05 % (Picato®) on trunk/extremities applied sequentially
Ingenol mebutate gel 0.015 %: Ingenol mebutate gel 0.015 % (Picato®) on face/scalp applied sequentially | 98 |
| Total | 199 |
Baseline characteristics
| Characteristic | Ingenol Mebutate Gel Simultaneous Treatment | Ingenol Mebutate Gel Sequential Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 89 Participants | 89 Participants | 178 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 9 Participants | 21 Participants |
| Age, Continuous | 74.4 years | 74.5 years | 74.5 years |
| Region of Enrollment Italy | 63 participants | 61 participants | 124 participants |
| Region of Enrollment Spain | 38 participants | 37 participants | 75 participants |
| Sex: Female, Male Female | 13 Participants | 18 Participants | 31 Participants |
| Sex: Female, Male Male | 88 Participants | 80 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 101 | 22 / 98 |
| serious Total, serious adverse events | 3 / 101 | 4 / 98 |
Outcome results
Primary
Composite Local Skin Reaction (LSR) Score 3 Days After Treatment of Each Selected Treatment Area
Composite Local Skin Reaction (LSR) score 3 days after treatment of each selected treatment area in both treatment groups (simultaneous or sequential). The composite LSR score (0 to 24), reflecting the sum of the individual LSR grades (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration, grade 0 to 4), was calculated for each selected treatment area at each visit.The composite LSR score ranges from 0 (best possible outcome) to 24 (worst possible outcome). Both affected areas were calculated together Per Arm. Each subject could contribute with up to 2 values (1 for each treated area).
Time frame: 3 days after treatment of each selected treatment area
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Composite Local Skin Reaction (LSR) Score 3 Days After Treatment of Each Selected Treatment Area | 10.4 units on a scale | Standard Deviation 5.1 |
| Ingenol Mebutate Gel Sequential Treatment | Composite Local Skin Reaction (LSR) Score 3 Days After Treatment of Each Selected Treatment Area | 9.7 units on a scale | Standard Deviation 4.5 |
p-value: 0.13Wilcoxon (Mann-Whitney)
Secondary
Complete Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment
Complete clearance of Actinic Keratosis lesions (AKs) analysed in each separate treatment area and presented by treatment regimen given as percentage of participants with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together Per Arm (e.g. averaged).
Time frame: 8 weeks after treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Complete Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 52.7 percentage of participants |
| Ingenol Mebutate Gel Sequential Treatment | Complete Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 46.9 percentage of participants |
p-value: 0.34Regression, Logistic
Secondary
Convenience TSQM
Convenience TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived convenience with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Convenience TSQM | 73.7 units on a scale | Standard Deviation 14.6 |
| Ingenol Mebutate Gel Sequential Treatment | Convenience TSQM | 74.7 units on a scale | Standard Deviation 18.1 |
p-value: 0.66Wilcoxon (Mann-Whitney)
Secondary
Effectiveness Satisfaction Questionnaire for Medication (TSQM)
Effectiveness TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived effectiveness of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Effectiveness Satisfaction Questionnaire for Medication (TSQM) | 63.1 units on a scale | Standard Deviation 23.4 |
| Ingenol Mebutate Gel Sequential Treatment | Effectiveness Satisfaction Questionnaire for Medication (TSQM) | 66.4 units on a scale | Standard Deviation 21.4 |
p-value: 0.38Wilcoxon (Mann-Whitney)
Secondary
Global Satisfaction TSQM
Global Satisfaction TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived overall satisfaction with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Global Satisfaction TSQM | 64.6 units on a scale | Standard Deviation 19 |
| Ingenol Mebutate Gel Sequential Treatment | Global Satisfaction TSQM | 67.4 units on a scale | Standard Deviation 20.3 |
p-value: 0.37Wilcoxon (Mann-Whitney)
Secondary
Partial Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment
Partial clearance of Actinic Keratosis lesions (AKs) defined as 75% or greater reduction in Actinic Keratosis lesions (AKs) from start of treatment to 8 weeks after treatment, was analysed in each separate treatment area and presented by treatment regimen given as percentage of participatns with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together Per Arm (e.g. averaged).
Time frame: 8 weeks after treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Partial Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 76.6 percentage of participants |
| Ingenol Mebutate Gel Sequential Treatment | Partial Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 68.1 percentage of participants |
p-value: 0.088Regression, Logistic
Secondary
Percent Reduction in Number of AKs in Each Separate Treatment Area 8 Weeks After Treatment
Percent reduction in number of Actinic Keratosis lesions (AKs) analysed for each separate treatment area and presented by treatment regimen. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together Per Arm (e.g. averaged).
Time frame: 8 weeks after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Percent Reduction in Number of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 83.4 percentage reduction in number of AKs | Standard Deviation 22 |
| Ingenol Mebutate Gel Sequential Treatment | Percent Reduction in Number of AKs in Each Separate Treatment Area 8 Weeks After Treatment | 79.1 percentage reduction in number of AKs | Standard Deviation 26.7 |
p-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
Side Effects TSQM
Side Effects TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived side effects of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel Simultaneous Treatment | Side Effects TSQM | 93.1 units on a scale | Standard Deviation 18.4 |
| Ingenol Mebutate Gel Sequential Treatment | Side Effects TSQM | 96.1 units on a scale | Standard Deviation 16.4 |
p-value: 0.033Wilcoxon (Mann-Whitney)