Actinic Keratoses
Conditions
Keywords
actinic keratoses, photodynamic therapy, natural daylight
Brief summary
This study was to be conducted as a multi-centre, randomized, investigator-blinded, active and vehicle-controlled, intra-individual (split-face/scalp) non-inferiority (regarding efficacy) and superiority (regarding pain) study. The primary purpose of this study is to demonstrate the non-inferiority of NDL-PDT compared to c-PDT in terms of lesion complete response rate.
Interventions
DRUGNDL-PDT
Metvix natural daylight photodynamic therapy
DRUGc-PDT
Metvix conventional photodynamic therapy
DRUGplacebo c-PDT
Metvix placebo conventional photodynamic therapy
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Intervention model description
2 intra-individual groups: * Metvix NDL-PDT / Metvix c-PDT * Metvix NDL-PDT / Placebo c-PDT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of mild (Grade 1) and/or moderate (Grade 2) AKs on the face or the scalp on treated areas * Subject with two symmetrical treated areas half scalps or two half faces excluding ears, chin, bridge of the nose, eyelids and lips inside the vermillion border): no more than a twofold difference in terms of total number of lesions between the two TAs
Exclusion criteria
* Subject with clinical diagnosis of at least one severe (Grade 3) AK on treated areas * Subject with pigmented AK on the treated areas * Immuno-compromised Subject for idiopathic, disease specific or therapeutic reasons * Subject with porphyria,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage (%) Change From Baseline in Total Lesion Complete Response at Week 12 in Group 1 | Baseline, Week 12 | The lesion complete response rate was defined as the percentage of pre-existing and treated lesions at Baseline that were assessed as clear (complete disappearance of the lesion, visually and by palpation) at Week 12. New lesions or the lesions in non-complete response were not not considered in the lesion response assessment. This outcome measure was analyzed as an intra-individual comparison between Metvix NDL-PDT on one side of the face/scalp and Metvix vehicle cream (placebo) c-PDT on the contralateral side (Group I). |
Countries
France, Germany, Netherlands, Spain, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Participants applied single dose of Metvix cream topically followed by NDL-PDT (test treatment) on one half-face/scalp and on the contra-lateral side of face/scalp applied Metvix cream topically followed by c- PDT (active comparator) on Day 0 (Baseline). | 108 |
| Group 2 Participants applied a single dose of Metvix cream topically followed by NDL-PDT (test treatment) on one half-face/scalp and on the contra-lateral side of face/scalp applied Metvix vehicle cream (placebo) followed by c-PDT on Day 0 (Baseline). | 23 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Group 2 | Group 1 |
|---|---|---|---|
| Age, Categorical Age <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Age >=65 years | 110 Participants | 21 Participants | 89 Participants |
| Age, Categorical Age Between 18 and 65 years | 21 Participants | 2 Participants | 19 Participants |
| Duration of AK (years) | 9.15 years STANDARD_DEVIATION 7.78 | 6.79 years STANDARD_DEVIATION 5.81 | 9.66 years STANDARD_DEVIATION 8.07 |
| Phototype Phototype I | 11 Participants | 1 Participants | 10 Participants |
| Phototype Phototype II | 86 Participants | 17 Participants | 69 Participants |
| Phototype Phototype III | 27 Participants | 3 Participants | 24 Participants |
| Phototype Phototype IV | 7 Participants | 2 Participants | 5 Participants |
| Race Other | 1 Participants | 1 Participants | 0 Participants |
| Race White | 130 Participants | 22 Participants | 108 Participants |
| Sex: Female, Male Female | 10 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 121 Participants | 22 Participants | 99 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 | 0 / 131 | 0 / 108 | 0 / 23 | 1 / 131 |
| other Total, other adverse events | 65 / 131 | 66 / 108 | 7 / 23 | 3 / 131 |
| serious Total, serious adverse events | 0 / 131 | 0 / 108 | 0 / 23 | 6 / 131 |
Outcome results
Primary
Percentage (%) Change From Baseline in Total Lesion Complete Response at Week 12 in Group 1
The lesion complete response rate was defined as the percentage of pre-existing and treated lesions at Baseline that were assessed as clear (complete disappearance of the lesion, visually and by palpation) at Week 12. New lesions or the lesions in non-complete response were not not considered in the lesion response assessment. This outcome measure was analyzed as an intra-individual comparison between Metvix NDL-PDT on one side of the face/scalp and Metvix vehicle cream (placebo) c-PDT on the contralateral side (Group I).
Time frame: Baseline, Week 12
Population: Intent-to-treat (ITT) population included entire population enrolled and randomized. ITT analysis imputed missing data using a worst case approach and considered the lesions with missed lesion response assessment as not responded (ITT/Worst-case) lesions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I: Metvix NDL-PDT | Percentage (%) Change From Baseline in Total Lesion Complete Response at Week 12 in Group 1 | 68.4 percentage change from baseline | Standard Deviation 27.7 |
| Group I: Metvix c-PDT | Percentage (%) Change From Baseline in Total Lesion Complete Response at Week 12 in Group 1 | 71.5 percentage change from baseline | Standard Deviation 27.6 |
p-value: =0.2665Paired Student's t test