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
DRUGLEO43204 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 (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), Weeks 4, and 8. Complete clearance was defined as no clinically visible AKs in the treatment area. The table shows the percentage of mean number of participants across imputations with complete clearance at Week 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Partial Clearance | At Week 8 | The number of clinically visible Actinic keratosis lesions (AKs) identified in the treatment area was recorded at Day 1, Weeks 4, and Week 8. Partial clearance was defined as at least 75% reduction from baseline in the number of clinically visible AKs in the treatment area. The table shows the percentage of mean number of participants across imputations with partial clearance at Week 8. |
| 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 (using multiple imputations to account for missing values). The table presents adjusted mean percent reduction at Week 8 from baseline. |
Countries
Germany
Participant flow
Recruitment details
391 participants were enrolled, 80 were screening failures, and 311 participants were randomized. Only 310 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 with LEO 43204 0.037% gel for 3 consecutive days applied on the scalp. | 209 |
| Vehicle Gel Treatment once daily with vehicle gel for 3 consecutive days applied on the scalp. | 101 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12-month Follow-up | Death | 0 | 1 |
| 12-month Follow-up | Lost to Follow-up | 3 | 2 |
| 12-month Follow-up | Other | 1 | 3 |
| 12-month Follow-up | Protocol Violation | 0 | 1 |
| 12-month Follow-up | Withdrawal by Subject | 4 | 5 |
| 3-day Treatment and 8-week Follow-up | Adverse Event | 0 | 1 |
| 3-day Treatment and 8-week Follow-up | Other | 0 | 2 |
| 3-day Treatment and 8-week Follow-up | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | LEO 43204 0.037% Gel | Vehicle Gel | Total |
|---|---|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 9 | 71.0 years STANDARD_DEVIATION 9.3 | 70.1 years STANDARD_DEVIATION 9.1 |
| Age, Customized Age group 18-64 years | 60 Participants | 17 Participants | 77 Participants |
| Age, Customized Age group 65-84 years | 139 Participants | 75 Participants | 214 Participants |
| Age, Customized Age group >=85 years | 10 Participants | 9 Participants | 19 Participants |
| Region of Enrollment Germany | 45 Participants | 25 Participants | 70 Participants |
| Region of Enrollment Italy | 23 Participants | 12 Participants | 35 Participants |
| Region of Enrollment United States | 141 Participants | 64 Participants | 205 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 209 Participants | 101 Participants | 310 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 | 146 / 210 | 12 / 100 | 5 / 208 | 1 / 92 |
| serious Total, serious adverse events | 3 / 210 | 3 / 100 | 0 / 208 | 0 / 92 |
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), Weeks 4, and 8. Complete clearance was defined as no clinically visible AKs in the treatment area. The table shows the percentage of mean number of participants across imputations with complete clearance at Week 8.
Time frame: At Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 43204 0.037% Gel | Percentage of Participants With Complete Clearance of Actinic Keratosis (AK) | 22.0 percentage of participants |
| Vehicle Gel | Percentage of Participants With Complete Clearance of Actinic Keratosis (AK) | 3.0 percentage of participants |
p-value: <0.00195% CI: [2.58, 23.71]Mantel Haenszel
Secondary
Percentage of Participants With Partial Clearance
The number of clinically visible Actinic keratosis lesions (AKs) identified in the treatment area was recorded at Day 1, Weeks 4, and Week 8. Partial clearance was defined as at least 75% reduction from baseline in the number of clinically visible AKs in the treatment area. The table shows the percentage of mean number of participants across imputations with partial clearance at Week 8.
Time frame: At Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 43204 0.037% Gel | Percentage of Participants With Partial Clearance | 63.1 percentage of participants |
| Vehicle Gel | Percentage of Participants With Partial Clearance | 11.0 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: [3.32, 10.51]Mantel Haenszel
Secondary
Percentage of Participants With Partial Clearance
The number of clinically visible Actinic keratosis lesions (AKs) identified in the treatment area was recorded at Day 1, Weeks 4, and Week 8. Partial clearance was defined as at least 75% reduction from baseline in the number of clinically visible AKs in the treatment area. The table shows the percentage of mean number of participants across imputations with partial clearance at Week 4.
Time frame: At Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 43204 0.037% Gel | Percentage of Participants With Partial Clearance | 53.4 percentage of participants |
| Vehicle Gel | Percentage of Participants With Partial Clearance | 7.1 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: [3.7, 15.61]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 (using multiple imputations to account for missing values). 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 | 74.0 percentage of change |
| Vehicle Gel | Percent Reduction in AK Count in the Treatment Area Compared to Baseline | 13.7 percentage of change |
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: [0.25, 0.36]Mantel Haenszel