Actinic Keratosis
Conditions
Keywords
Actinic Keratoses, Actinic Keratosis, Photodynamic Therapy
Brief summary
The goal of this clinical trial is to see if shorter Photodynamic Therapy (PDT) treatment times will still be effective at treating actinic keratoses (AK) while reducing or eliminating the pain that patients sometimes experience during conventional PDT treatment. The main questions it aims to answer are: * Will the application of the nanoemulsion (10% ALA gel), in the absence of occlusion, still achieve significant inflammation and lesion clearance? * Will shortened incubation times of Ameluz still achieve significant inflammation and lesion clearance? * Will the new test regimens achieve reduced pain during illumination? * Will the new test regimens be safe? Participants will be randomly assigned to one of three treatment regimens, which will determine the length of time that the topical medication will incubate on the face before red light exposure in PDT treatments. The incubation period will be either 10 minutes, 20 minutes, or 60 minutes.
Interventions
DRUGTopical aminolevulinate (10% ALA gel)
10% ALA gel to the entire face, without occlusion, followed by a prespecified incubation period
DEVICERed light illumination
Illumination of red light of narrow spectrum of 635 nm with a light dose of approximately 37 J/cm2
Sponsors
The Cleveland Clinic
Biofrontera Inc.
Case Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Minimum of 10 actinic keratoses lesions on the face. * Female subjects must not become pregnant during the study * Subjects must be able to understand and willing to sign a written informed consent document.
Exclusion criteria
* Pregnant or nursing. * Using any topical treatment on their AKs; must stop at least one month prior. * Currently undergoing treatment for other cancers with medical or radiation therapy. * Patients with a known hypersensitivity to 5-aminolevulinic acid or any component of the study material. * Patients with history of a photosensitivity disease, such as porphyria cutanea tarda.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Efficacy Based on Participant AK Lesion Clearance | Lesion clearance at Visit 3 (month 2) and at Visit 4 (month 6) | To test the hypothesis that a short-contact PDT protocol with Ameluz and red light will produce lesion clearance outcomes that are statistically non-inferior to the traditional, painful protocol. This will be measured by Clinical Efficacy, which will be based on the AK lesion counts and lesion clearance rate after two treatments. |
| Differences in Pain Level Reported Throughout Exposure to Red Light | Pain measured during illumination with red light (during a 10 min period) at Visit 1 (Day 3) and at Visit 3 (Month 2) | Pain will be reported by the participants during illumination will be measured on a subjective 11-point visual-analog scale (VAS scale 0= no pain, 10 = intolerable pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Satisfaction Survey as Measured by Treatment Outcome Score | 6 months | Treatment score on a scale of 0 to 5, where 0 indicates extremely dissatisfied and 5 indicates extremely satisfied. |
| Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | At month 6 | Cosmetic score on a scale of 0 to 5, where 0 indicates extremely dissatisfied and 5 indicates extremely satisfied. |
| Number of Participant Reported Adverse Events and Side Effects | Up to 6 days (Day 6) after Visit 1 | Overall AE Profile and Safety of treatment will be measured using an Adverse Events- Patients' side effects log and Investigator assessment. |
Countries
United States
Participant flow
Recruitment details
A total of 10 subjects are enrolled for each of the study arms A, B, and C.
Participants by arm
| Arm | Count |
|---|---|
| Regimen A Apply topical aminolevulinic acid gel and incubate for 10 minutes prior to red light source
Topical aminolevulinate (10% ALA gel): 10% ALA gel to the entire face, without occlusion, followed by a prespecified incubation period
Red light illumination: Illumination of red light of narrow spectrum of 635 nm with a light dose of approximately 37 J/cm2 | 10 |
| Regimen B Apply topical aminolevulinic acid gel and incubate for 20 minutes prior to red light source
Topical aminolevulinate (10% ALA gel): 10% ALA gel to the entire face, without occlusion, followed by a prespecified incubation period
Red light illumination: Illumination of red light of narrow spectrum of 635 nm with a light dose of approximately 37 J/cm2 | 10 |
| Regimen C Apply topical aminolevulinic acid gel and incubate for 60 minutes prior to red light source
Topical aminolevulinate (10% ALA gel): 10% ALA gel to the entire face, without occlusion, followed by a prespecified incubation period
Red light illumination: Illumination of red light of narrow spectrum of 635 nm with a light dose of approximately 37 J/cm2 | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Regimen A | Regimen B | Regimen C | Total |
|---|---|---|---|---|
| Age, Continuous | 69.3 years STANDARD_DEVIATION 7.4 | 69.9 years STANDARD_DEVIATION 7 | 71.2 years STANDARD_DEVIATION 5.8 | 70.1 years STANDARD_DEVIATION 0.97 |
| AK lesions | 54.8 Lesions STANDARD_DEVIATION 24.3 | 37.1 Lesions STANDARD_DEVIATION 17.3 | 46.3 Lesions STANDARD_DEVIATION 17.3 | 46.07 Lesions STANDARD_DEVIATION 8.85 |
| AKs previously | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| History of skin cancer | 9 Participants | 8 Participants | 7 Participants | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 7 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Differences in Pain Level Reported Throughout Exposure to Red Light
Pain will be reported by the participants during illumination will be measured on a subjective 11-point visual-analog scale (VAS scale 0= no pain, 10 = intolerable pain)
Time frame: Pain measured during illumination with red light (during a 10 min period) at Visit 1 (Day 3) and at Visit 3 (Month 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Differences in Pain Level Reported Throughout Exposure to Red Light | Pain at visit 1 | 0.70 score on a scale | Standard Error 0.32 |
| Regimen A | Differences in Pain Level Reported Throughout Exposure to Red Light | Pain at visit 3 | 0.20 score on a scale | Standard Error 0.21 |
| Regimen B | Differences in Pain Level Reported Throughout Exposure to Red Light | Pain at visit 1 | 0.10 score on a scale | Standard Error 0.11 |
| Regimen B | Differences in Pain Level Reported Throughout Exposure to Red Light | Pain at visit 3 | 0.30 score on a scale | Standard Error 0.16 |
| Regimen C | Differences in Pain Level Reported Throughout Exposure to Red Light | Pain at visit 1 | 4.7 score on a scale | Standard Error 0.65 |
| Regimen C | Differences in Pain Level Reported Throughout Exposure to Red Light | Pain at visit 3 | 2.22 score on a scale | Standard Error 0.68 |
Primary
Treatment Efficacy Based on Participant AK Lesion Clearance
To test the hypothesis that a short-contact PDT protocol with Ameluz and red light will produce lesion clearance outcomes that are statistically non-inferior to the traditional, painful protocol. This will be measured by Clinical Efficacy, which will be based on the AK lesion counts and lesion clearance rate after two treatments.
Time frame: Lesion clearance at Visit 3 (month 2) and at Visit 4 (month 6)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regimen A | Treatment Efficacy Based on Participant AK Lesion Clearance | Lesion clearance rate at Visit 3 | 59 percentage of AK lesions |
| Regimen A | Treatment Efficacy Based on Participant AK Lesion Clearance | Lesion clearance rate at Visit 4 | 76 percentage of AK lesions |
| Regimen B | Treatment Efficacy Based on Participant AK Lesion Clearance | Lesion clearance rate at Visit 3 | 34 percentage of AK lesions |
| Regimen B | Treatment Efficacy Based on Participant AK Lesion Clearance | Lesion clearance rate at Visit 4 | 74 percentage of AK lesions |
| Regimen C | Treatment Efficacy Based on Participant AK Lesion Clearance | Lesion clearance rate at Visit 3 | 43 percentage of AK lesions |
| Regimen C | Treatment Efficacy Based on Participant AK Lesion Clearance | Lesion clearance rate at Visit 4 | 82 percentage of AK lesions |
Secondary
Number of Participant Reported Adverse Events and Side Effects
Overall AE Profile and Safety of treatment will be measured using an Adverse Events- Patients' side effects log and Investigator assessment.
Time frame: Up to 6 days (Day 6) after Visit 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regimen A | Number of Participant Reported Adverse Events and Side Effects | Side effects | 9 Number of events |
| Regimen A | Number of Participant Reported Adverse Events and Side Effects | Adverse events | 0 Number of events |
| Regimen B | Number of Participant Reported Adverse Events and Side Effects | Adverse events | 0 Number of events |
| Regimen B | Number of Participant Reported Adverse Events and Side Effects | Side effects | 10 Number of events |
| Regimen C | Number of Participant Reported Adverse Events and Side Effects | Adverse events | 2 Number of events |
| Regimen C | Number of Participant Reported Adverse Events and Side Effects | Side effects | 9 Number of events |
Secondary
Patient Satisfaction Survey as Measured by Cosmetic Outcome Score
Cosmetic score on a scale of 0 to 5, where 0 indicates extremely dissatisfied and 5 indicates extremely satisfied.
Time frame: At month 6
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regimen A | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 2 | 0 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 3 | 10 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 5 | 70 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 4 | 20 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 1 | 0 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 3 | 10 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 5 | 50 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 4 | 40 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 2 | 0 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 1 | 0 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 1 | 0 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 2 | 0 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 5 | 89 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 3 | 11 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Cosmetic Outcome Score | Percentage of participants giving a score of 4 | 0 percentage of patients |
Secondary
Patient Satisfaction Survey as Measured by Treatment Outcome Score
Treatment score on a scale of 0 to 5, where 0 indicates extremely dissatisfied and 5 indicates extremely satisfied.
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regimen A | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 2 | 0 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 3 | 10 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 5 | 80 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 4 | 10 percentage of patients |
| Regimen A | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 1 | 0 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 3 | 10 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 5 | 60 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 4 | 30 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 2 | 0 percentage of patients |
| Regimen B | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 1 | 0 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 1 | 0 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 2 | 0 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 5 | 89 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 3 | 0 percentage of patients |
| Regimen C | Patient Satisfaction Survey as Measured by Treatment Outcome Score | Percentages of patients giving a score of 4 | 11 percentage of patients |