Actinic Keratoses
Conditions
Brief summary
A Randomized, Double-Blind, Vehicle-Controlled, Multicenter Study to Assess the Efficacy and Safety of Methyl aminolevulinate hydrochloride (MAL) 16.8% cream (CD06809-41) versus vehicle cream in the treatment of thin and moderately thick, non-hyperkeratotic, non-pigmented actinic keratosis of the face and scalp when using daylight photodynamic therapy (DL-PDT).
Detailed description
This was a randomized, double-blind, vehicle-controlled, multicenter, parallel-group study in adult participants with clinically-confirmed mild to moderate AKs on the face and the balding scalp, to be conducted at approximately 60 clinical sites in the United States. Sites were selected to ensure that diverse daylight conditions represented in the study to understand the effects of latitude, elevation, and climate.
Interventions
DRUGMAL 16.8% cream
Day light photodynamic therapy with MAL 16.8% cream
DRUGMAL Vehicle Cream
Day light photodynamic therapy with MAL vehicle cream
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants aged ≥ 18 years at the Screening visit. * Participants had at least 4, but no more than 12, clinically-confirmed thin or moderately thick, non-hyperkeratotic, non-pigmented AKs located on the face (e.g., forehead, cheek, chin), and balding scalp. * Female Participants of non-childbearing potential. * Participants fully understood and signed an ICF before any investigational procedure(s) are performed.
Exclusion criteria
* Participants with pigmented AK in the treatment areas. * Female participants who were pregnant, nursing, or planning a pregnancy during the study. * Participants with a clinical diagnosis of a skin disease other than AK. * Immunocompromised participants. * Participants with any condition that may be associated with a risk of poor protocol compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response at Week 12 | Week 12 | Complete response was defined as clearance of all AK lesion treated, at week 12 after the last Daylight photodynamic therapy (DL-PDT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lesion Complete Response at Week 12 | Baseline, Week 12 | Lesion complete response was defined as percent reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment. This outcome measure was analyzed as an intra-individual comparison between MAL cream and Vehicle cream. |
| Percentage of Participants With Partial Response at Week 12 | Week 12 | Participants achieving partial response was defined as participants with 75% or greater reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment, comparing MAL cream with vehicle cream. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
A total of 557 participants were randomized in 2:1 ratio in two treatment group, MAL 16.8% cream and vehicle cream in study centers in the United States with diverse latitude, altitude, and climate characteristics.
Participants by arm
| Arm | Count |
|---|---|
| MAL 16.8% Cream Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (Daylight photodynamic therapy \[DL-PDT\]). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser. | 364 |
| MAL Vehicle Cream Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of vehicle cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (DL-PDT). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser. | 193 |
| Total | 557 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Other unspecified | 2 | 1 |
| Overall Study | Status Unknown | 1 | 1 |
| Overall Study | Withdrawal by Subject | 13 | 4 |
Baseline characteristics
| Characteristic | MAL Vehicle Cream | Total | MAL 16.8% Cream |
|---|---|---|---|
| Age, Continuous | 68.9 years STANDARD_DEVIATION 9 | 69.1 years STANDARD_DEVIATION 8.83 | 69.2 years STANDARD_DEVIATION 8.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 48 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 177 Participants | 504 Participants | 327 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 192 Participants | 551 Participants | 359 Participants |
| Sex: Female, Male Female | 61 Participants | 159 Participants | 98 Participants |
| Sex: Female, Male Male | 132 Participants | 398 Participants | 266 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 364 | 0 / 193 |
| other Total, other adverse events | 89 / 364 | 41 / 193 |
| serious Total, serious adverse events | 5 / 364 | 1 / 193 |
Outcome results
Primary
Percentage of Participants With Complete Response at Week 12
Complete response was defined as clearance of all AK lesion treated, at week 12 after the last Daylight photodynamic therapy (DL-PDT).
Time frame: Week 12
Population: ITT analysis population included all participants randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MAL 16.8% Cream | Percentage of Participants With Complete Response at Week 12 | 25.3 percentage of participants |
| MAL Vehicle Cream | Percentage of Participants With Complete Response at Week 12 | 23.0 percentage of participants |
Secondary
Percentage of Participants With Partial Response at Week 12
Participants achieving partial response was defined as participants with 75% or greater reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment, comparing MAL cream with vehicle cream.
Time frame: Week 12
Population: ITT analysis population included all participants randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MAL 16.8% Cream | Percentage of Participants With Partial Response at Week 12 | 48.2 percentage of participants |
| MAL Vehicle Cream | Percentage of Participants With Partial Response at Week 12 | 35.1 percentage of participants |
Secondary
Percent Change From Baseline in Lesion Complete Response at Week 12
Lesion complete response was defined as percent reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment. This outcome measure was analyzed as an intra-individual comparison between MAL cream and Vehicle cream.
Time frame: Baseline, Week 12
Population: ITT analysis population included all participants randomized in the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MAL 16.8% Cream | Percent Change From Baseline in Lesion Complete Response at Week 12 | -61.1 percent change | Standard Error 1.79 |
| MAL Vehicle Cream | Percent Change From Baseline in Lesion Complete Response at Week 12 | -49.4 percent change | Standard Error 2.45 |