Actinic Keratosis
Conditions
Brief summary
The objective of the trial is to compare the short term efficacy of LEO 43204 gel with vehicle gel in AK on the balding scalp when applied topically once daily for 3 consecutive days as field treatment.
Interventions
DRUGLEO 43204 gel
DRUGVehicle gel
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with 5 to 20 clinically typical, visible and discrete AKs within a treatment area of sun-damaged skin on the full balding scalp (the balding part of the scalp should be greater than 25 cm2 (4 in2) and up to approximately 250 cm2 (40 In2) * Subjects with minimum 3 clinically typical, visible and discrete AKs within a tracking area of 50 cm2 (8 In2). The tracking area must be within the treatment area
Exclusion criteria
* Location of the treatment area (full balding scalp) within 5 cm of an incompletely healed wound or within 5 cm of a suspected BCC or SCC * Treatment with ingenol mebutate gel in the treatment area within the last 12 months * Lesions in the treatment area that have: atypical clinical appearance (e.g. hyperthrophic, hyperkeratotic or cutaneous horns) and /or, 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Clearance of Actinic Keratosis (AK) | At Week 8 | The number of clinically visible actinic keratosis lesions (AKs) identified in the treatment area was recorded at Day 1 (baseline), Week 4 and Week 8. Complete clearance was defined as no clinically visible AKs in the treatment area. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Partial Clearance of AKs | At Week 8 | Partial clearance was defined as at least 75% reduction from baseline in the number of clinically visible AKs in the treatment area. |
| Percent Reduction in AK Count in the Treatment Area Compared to Baseline | At Week 8 | The percent reduction at Week 8 from baseline was analysed using a negative binomial regression for the AK count at Week 8 with treatment group and pooled sites as factors and baseline count as offset variable. The table presents adjusted mean percent reduction at Week 8 from baseline. |
Countries
United States
Participant flow
Recruitment details
373 participants were enrolled, 57 were screening failures, and 316 participants were randomized. Only 313 of the randomized participants were treated with investigational medicinal product (IMP), the number of participants treated is reflected as the number of participants started in the first period.
Participants by arm
| Arm | Count |
|---|---|
| LEO 43204 0.037% Gel Treatment once daily for 3 days with LEO 43204 0.037% gel | 209 |
| Vehicle Gel Treatment once daily for 3 days with vehicle gel | 104 |
| Total | 313 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12-month Follow-up | Lack of Efficacy | 1 | 1 |
| 12-month Follow-up | Lost to Follow-up | 4 | 1 |
| 12-month Follow-up | Other | 1 | 0 |
| 12-month Follow-up | Withdrawal by Subject | 4 | 3 |
| 3-day Treatment and 8-week Follow-up | Adverse Event | 0 | 1 |
| 3-day Treatment and 8-week Follow-up | Lost to Follow-up | 1 | 1 |
| 3-day Treatment and 8-week Follow-up | Other | 1 | 1 |
| 3-day Treatment and 8-week Follow-up | Withdrawal by Subject | 2 | 8 |
Baseline characteristics
| Characteristic | LEO 43204 0.037% Gel | Vehicle Gel | Total |
|---|---|---|---|
| Age, Continuous | 70.9 years STANDARD_DEVIATION 9.1 | 69.9 years STANDARD_DEVIATION 9.3 | 70.5 years STANDARD_DEVIATION 9.2 |
| Age, Customized Age group 18-64 years | 45 Participants | 28 Participants | 73 Participants |
| Age, Customized Age group 65-84 years | 155 Participants | 70 Participants | 225 Participants |
| Age, Customized Age group >=85 years | 9 Participants | 6 Participants | 15 Participants |
| Region of Enrollment Canada | 69 Participants | 37 Participants | 106 Participants |
| Region of Enrollment France | 13 Participants | 7 Participants | 20 Participants |
| Region of Enrollment United Kingdom | 18 Participants | 9 Participants | 27 Participants |
| Region of Enrollment United States | 109 Participants | 51 Participants | 160 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 208 Participants | 104 Participants | 312 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 153 / 209 | 9 / 104 | 18 / 204 | 12 / 86 |
| serious Total, serious adverse events | 4 / 209 | 2 / 104 | 1 / 204 | 0 / 86 |
Outcome results
Primary
Percentage of Participants With Complete Clearance of Actinic Keratosis (AK)
The number of clinically visible actinic keratosis lesions (AKs) identified in the treatment area was recorded at Day 1 (baseline), Week 4 and Week 8. Complete clearance was defined as no clinically visible AKs in the treatment area.
Time frame: At Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 43204 0.037% Gel | Percentage of Participants With Complete Clearance of Actinic Keratosis (AK) | 25.8 percentage of participants |
| Vehicle Gel | Percentage of Participants With Complete Clearance of Actinic Keratosis (AK) | 0.0 percentage of participants |
p-value: <0.001Fisher exact test
Secondary
Percentage of Participants With Partial Clearance of AKs
Partial clearance was defined as at least 75% reduction from baseline in the number of clinically visible AKs in the treatment area.
Time frame: At Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 43204 0.037% Gel | Percentage of Participants With Partial Clearance of AKs | 58.9 percentage of participants |
| Vehicle Gel | Percentage of Participants With Partial Clearance of AKs | 1.0 percentage of participants |
Comparison: The p-values for secondary endpoints have been corrected by the Holm-Bonferroni method to account for multiplicity. The prespecified multiplicity adjustment by the Holm-Bonferroni method requires the ordering of the p-values for the secondary endpoints by size.p-value: <0.00195% CI: [8.68, 451.08]Mantel Haenszel
Secondary
Percentage of Participants With Partial Clearance of AKs
Partial clearance was defined as at least 75% reduction from baseline in the number of clinically visible AKs in the treatment area.
Time frame: At Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 43204 0.037% Gel | Percentage of Participants With Partial Clearance of AKs | 57.4 percentage of participants |
| Vehicle Gel | Percentage of Participants With Partial Clearance of AKs | 1.0 percentage of participants |
Comparison: The p-values for secondary endpoints have been corrected by the Holm-Bonferroni method to account for multiplicity. The prespecified multiplicity adjustment by the Holm-Bonferroni method requires the ordering of the p-values for the secondary endpoints by size.p-value: <0.00195% CI: [8.44, 415.35]Mantel Haenszel
Secondary
Percent Reduction in AK Count in the Treatment Area Compared to Baseline
The percent reduction at Week 8 from baseline was analysed using a negative binomial regression for the AK count at Week 8 with treatment group and pooled sites as factors and baseline count as offset variable. The table presents adjusted mean percent reduction at Week 8 from baseline.
Time frame: At Week 8
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LEO 43204 0.037% Gel | Percent Reduction in AK Count in the Treatment Area Compared to Baseline | 72.3 percentage of reduction |
| Vehicle Gel | Percent Reduction in AK Count in the Treatment Area Compared to Baseline | -2.0 percentage of reduction |
Comparison: The p-values for secondary endpoints have been corrected by the Holm-Bonferroni method to account for multiplicity. The prespecified multiplicity adjustment by the Holm-Bonferroni method requires the ordering of the p-values for the secondary endpoints by size.p-value: <0.00195% CI: [0.23, 0.32]Mantel Haenszel