Actinic Keratosis
Conditions
Brief summary
The objective of the trial is to investigate the Safety of LEO 43204 0.018%, 0.037% and 0.1% for actinic keratosis applied once daily for three consecutive days on face/chest, scalp and trunk/extremities, respectively.
Interventions
DRUGLEO 43204
Treatment of actinic keratosis
Sponsors
LEO Pharma
Study design
Allocation
NON_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 with 5 to 20 clinically typical, visible and, discrete, nonhyperkeratotic and non-hypertrophic AKs within a selected treatment area of sun-damaged skin on either: * The full face * The full balding scalp * A contiguous area of approximately 250 cm2 on trunk or extremities
Exclusion criteria
Location of the treatment area (full face, full balding scalp or chest) within 5 cm of an incompletely healed wound or within 5 cm of a suspected basal cell carcinoma (BCC) or SCC. Previously assigned treatment in this clinical trial or previously participated in a clinical trial in the LEO 43204 programme. Treatment with ingenol mebutate gel in the selected treatment area within the last 12 months Lesions in the treatment area that have: atypical clinical appearance (e.g. cutaneous horns) and/or, recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing DLTs (Dose Limiting Toxicities) Based on LSRs (Local Skin Reactions) | 8 days / From baseline (Day 1) to Day 8 | For face/chest, a DLT was defined as one or more of the following three 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 For scalp a DLT was defined as erosion/ulceration Grade 4 For trunk/extremities a DLT was defined as one or more of the following three LSRs: * Crusting Grade 4 * Erosion/Ulceration Grade 4 * Vesiculation/Pustulation Grade 4 Or two or more of the following four LSRs: * Crusting Grade 3 * Swelling Grade 4 * Erosion/Ulceration Grade 3 * Vesiculation/Pustulation Grade 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | 4 weeks and 8 weeks / From baseline to Week 4, and Week 8 | The number of clinically visible actinic keratosis lesions (AKs) identified in the treatment area was recorded at baseline (Day 1), Week 4, and Week 8. This analysis excluded lesions identified at baseline as hypertrophic/hyperkeratotic. |
| Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | 4 weeks and 8 weeks / From baseline to Week 4, and Week 8 | Hypertrophic/Hyperkeratotic lesions were identified at baseline (Day 1), Week 4 and Week 8. |
| Percentage of Participants With Complete Clearance of AKs | 8 weeks | Complete clearance was defined as no clinically visible AKs. This analysis excluded lesions identified at baseline as hypertrophic/hyperkeratotic. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LEO 43204 0.018% Face/Chest Treatment with LEO 43204 0.018% gel once daily for 3 consecutive days on the full face or a contiguous area on the chest of approximately 250 cm2. | 63 |
| LEO 43204 0.037% Scalp Treatment with LEO 43204 0.037% gel once daily for 3 consecutive days on the full balding scalp of an area greater than 25 cm2 and up to approximately 250 cm2. | 63 |
| LEO 43204 0.1% Trunk/Extremities Treatment with LEO 43204 0.1% gel once daily for 3 consecutive days on a contiguous area of approximately 250 cm2 on trunk or extremities (excluding chest). | 62 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | LEO 43204 0.018% Face/Chest | LEO 43204 0.037% Scalp | LEO 43204 0.1% Trunk/Extremities | Total |
|---|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 8.8 | 67.7 years STANDARD_DEVIATION 9.6 | 66.7 years STANDARD_DEVIATION 9.6 | 66.2 years STANDARD_DEVIATION 9.4 |
| Region of Enrollment United States | 63 participants | 63 participants | 62 participants | 188 participants |
| Sex: Female, Male Female | 23 Participants | 1 Participants | 23 Participants | 47 Participants |
| Sex: Female, Male Male | 40 Participants | 62 Participants | 39 Participants | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 63 | 47 / 63 | 43 / 62 |
| serious Total, serious adverse events | 1 / 63 | 0 / 63 | 0 / 62 |
Outcome results
Primary
Number of Participants Experiencing DLTs (Dose Limiting Toxicities) Based on LSRs (Local Skin Reactions)
For face/chest, a DLT was defined as one or more of the following three 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 For scalp a DLT was defined as erosion/ulceration Grade 4 For trunk/extremities a DLT was defined as one or more of the following three LSRs: * Crusting Grade 4 * Erosion/Ulceration Grade 4 * Vesiculation/Pustulation Grade 4 Or two or more of the following four LSRs: * Crusting Grade 3 * Swelling Grade 4 * Erosion/Ulceration Grade 3 * Vesiculation/Pustulation Grade 3
Time frame: 8 days / From baseline (Day 1) to Day 8
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LEO 43204 0.018% Face/Chest | Number of Participants Experiencing DLTs (Dose Limiting Toxicities) Based on LSRs (Local Skin Reactions) | 9 Participants |
| LEO 43204 0.037% Scalp | Number of Participants Experiencing DLTs (Dose Limiting Toxicities) Based on LSRs (Local Skin Reactions) | 0 Participants |
| LEO 43204 0.1% Trunk/Extremities | Number of Participants Experiencing DLTs (Dose Limiting Toxicities) Based on LSRs (Local Skin Reactions) | 11 Participants |
Secondary
Percentage of Participants With Complete Clearance of AKs
Complete clearance was defined as no clinically visible AKs. This analysis excluded lesions identified at baseline as hypertrophic/hyperkeratotic.
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 43204 0.018% Face/Chest | Percentage of Participants With Complete Clearance of AKs | 36.5 percentage of participants |
| LEO 43204 0.037% Scalp | Percentage of Participants With Complete Clearance of AKs | 39.7 percentage of participants |
| LEO 43204 0.1% Trunk/Extremities | Percentage of Participants With Complete Clearance of AKs | 22.6 percentage of participants |
Secondary
Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic
The number of clinically visible actinic keratosis lesions (AKs) identified in the treatment area was recorded at baseline (Day 1), Week 4, and Week 8. This analysis excluded lesions identified at baseline as hypertrophic/hyperkeratotic.
Time frame: 4 weeks and 8 weeks / From baseline to Week 4, and Week 8
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LEO 43204 0.018% Face/Chest | Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 4 | 81.2 percentage of reduction |
| LEO 43204 0.018% Face/Chest | Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 8 | 78.9 percentage of reduction |
| LEO 43204 0.037% Scalp | Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 4 | 78.8 percentage of reduction |
| LEO 43204 0.037% Scalp | Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 8 | 76.3 percentage of reduction |
| LEO 43204 0.1% Trunk/Extremities | Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 4 | 59.0 percentage of reduction |
| LEO 43204 0.1% Trunk/Extremities | Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 8 | 69.1 percentage of reduction |
Secondary
Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic
Hypertrophic/Hyperkeratotic lesions were identified at baseline (Day 1), Week 4 and Week 8.
Time frame: 4 weeks and 8 weeks / From baseline to Week 4, and Week 8
Population: For this efficacy analysis only participants with lesions identified as hypertrophic/hyperkeratotic at baseline were included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LEO 43204 0.018% Face/Chest | Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 4 | 78.7 percentage of reduction |
| LEO 43204 0.018% Face/Chest | Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 8 | 68.5 percentage of reduction |
| LEO 43204 0.037% Scalp | Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 4 | 58.1 percentage of reduction |
| LEO 43204 0.037% Scalp | Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 8 | 62.5 percentage of reduction |
| LEO 43204 0.1% Trunk/Extremities | Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 4 | 36.0 percentage of reduction |
| LEO 43204 0.1% Trunk/Extremities | Percent Reduction in AK Count of Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic | Week 8 | 39.2 percentage of reduction |