Actinic Keratosis
Conditions
Keywords
Imiquimod, Photodynamic therapy, Actinic keratoses, Sequential therapy, Therapeutic uses
Brief summary
The purpose of this study is to explore the effect of treating actinic keratoses of the face with imiquimod 3.75% cream followed by photodynamic therapy in comparison to treatment with imiquimod alone
Detailed description
Actinic keratoses are common skin lesions associated with solar ultraviolet radiation exposure. Some actinic keratoses may develop into skin cancers. Imiquimod 3.75% cream is an approved treatment for actinic keratoses that utilizes a regimen of application to the entire face or balding scalp of up to 2 packets of cream daily for two 2-week cycles, separated by a 2-week no treatment interval. Photodynamic therapy with aminolevulinic acid (ALA) 20% topical solution is also an approved treatment for actinic keratoses. ALA is applied to actinic keratoses, and after an incubation period, is excited with light. Although approved as a lesion-directed treatment for actinic keratoses, treatment of a field (e.g. face) with photodynamic therapy is commonly performed. Treatment with photodynamic therapy followed by imiquimod 5% cream has been reported in patients with actinic keratoses, basal cell carcinoma and Bowen's disease, and treatment with imiquimod 5% cream followed by photodynamic therapy in patients with vulvar intraepithelial neoplasia. There are, however, no prior studies on the safety and/or efficacy of using topical imiquimod 3.75% in conjunction with photodynamic therapy in the treatment of actinic keratoses. This study will use an open-label parallel cohort design in which all patients will received treatment with imiquimod 3.75% cream, and subsequently will be randomized to either photodynamic therapy or observation.
Interventions
DRUGPhotodynamic therapy
Administered 4 weeks after completion of imiquimod therapy
DRUGImiquimod
Imiquimod 3.75% cream, up to 2 packets, applied topically daily for two 2-week cycles separated by a no-treatment interval of 2-weeks, followed observation
Sponsors
Graceway Pharmaceuticals, LLC
Tennessee Clinical Research 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
* Male and female adults; 18 and over * At least 10 and no more than 30 clinically typical actinic keratoses on the face
Exclusion criteria
* Hypertrophic actinic keratoses or other skin lesions on the head that might required excluded treatment during the study * Known contraindication to treatment with imiquimod or photodynamic therapy * Condition that would limit compliance, be a potential safety risk, or require therapy with an excluded treatment * Systemically immunocompromised * Pregnant or nursing * Dermatologic disease and/or condition in treatment area that might exacerbated by treatment with imiquimod, cause difficulty with examination, or require therapy with an excluded treatment * Participation in another clinical study * Treatment within the past 60 days with: * Ultraviolet therapy * Systemic immunomodulators * Chemotherapeutic or cytotoxic agents * Investigational agents * Treatment on the head within the past 60 days with: * Imiquimod * Photodynamic therapy * Red or blue light source therapy * Cryotherapy or chemotherapy * Surgical excision or curettage * Topical corticosteroids * Laser * Dermabrasion * Chemical peel * Topical retinoids * Topical 5-fluorouracil * Topical pimecrolimus or tacrolimus * Topical diclofenac * Treatment for actinic keratoses on the head within the past 60 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Actinic Keratosis Count | Week 18 (4 weeks after randomization visit) | The percent change in actinic keratosis count as compared to the baseline lesion count |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Clearance | Week 18 (4 weeks after randomization visit) | The proportion of randomized patients with complete clearance of actinic keratoses in the treatment area (entire face). |
| Cosmetic Appearance | Week 18 (4 weeks after randomization visit) | Change (improvement) in investigator scores of cosmetic appearance of the treatment area (entire face) by objective and subjective assessments: INVESTIGATOR COSMETIC ASSESSMENT 0 - Facial skin is smooth to the touch, without significant lines or unevenness in pigmentation 1 - Facial skin shows 1 area (cheeks, forehead, or the perioral area) of significant 3 - Facial skin shows 3 areas with significant roughness, dyspigmentation, or fine lines 2 - Facial skin shows 2 areas of significant roughness, dyspigmentation, or fine lines 4 - All are severe in severity |
Countries
United States
Participant flow
Recruitment details
Patients recruited from practices of 3 dermatology clinics. First patient enrolled Nov 2010; last patient completed Dec 2011.
Pre-assignment details
Patients required to complete topical treatment phase prior to randomization to photodynamic therapy or observation. Three subjects discontinued prior to randomization, 2 for adverse events and 1 for withdrawal of consent.
Participants by arm
| Arm | Count |
|---|---|
| Imiquimod Followed by Photodynamic Therapy Imiquimod 3.75% applied to the entire face daily for 2 2-week cycles separated by a 2-week no treatment period, followed by one session of photodynamic therapy of the entire face with aminolevulinic acid and blue light | 9 |
| Imiquimod Followed by Observation Imiquimod 3.75% applied to the entire face daily for 2 2-week cycles separated by a 2-week no treatment period, followed by observation | 9 |
| Non-Randomized Imiquimod 3.75% applied to the entire face daily for up to 2 2-week cycles separated by a 2-week no treatment period, | 3 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Imiquimod Followed by Photodynamic Therapy | Total | Non-Randomized | Imiquimod Followed by Observation |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 7 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 14 Participants | 2 Participants | 6 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 7 | 62 years STANDARD_DEVIATION 7 | 66 years STANDARD_DEVIATION 11 | 61 years STANDARD_DEVIATION 6 |
| Region of Enrollment United States | 9 participants | 21 participants | 3 participants | 9 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 2 Participants | 6 Participants |
| Total facial actinic keratosis count | 18.3 Patient facial actinic keratosis count STANDARD_DEVIATION 5.6 | 19.0 Patient facial actinic keratosis count STANDARD_DEVIATION 5.1 | 18.0 Patient facial actinic keratosis count STANDARD_DEVIATION 2.6 | 19.9 Patient facial actinic keratosis count STANDARD_DEVIATION 5.6 |
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 | 5 / 9 | 4 / 9 | 2 / 3 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 3 |
Outcome results
Primary
Actinic Keratosis Count
The percent change in actinic keratosis count as compared to the baseline lesion count
Time frame: Week 18 (4 weeks after randomization visit)
Population: Randomized patients with both a baseline and a week 18 actinic keratosis count. One patient in imiquimod/observation group did not have a baseline count and therefore was not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imiquimod Followed by Photodynamic Therapy | Actinic Keratosis Count | 81 percent reduction in baseline count | Standard Deviation 19 |
| Imiquimod Followed by Observation | Actinic Keratosis Count | 83 percent reduction in baseline count | Standard Deviation 34 |
Secondary
Complete Clearance
The proportion of randomized patients with complete clearance of actinic keratoses in the treatment area (entire face).
Time frame: Week 18 (4 weeks after randomization visit)
Population: Randomized patients with a week 18 actinic keratosis count.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imiquimod Followed by Photodynamic Therapy | Complete Clearance | 5 participants |
| Imiquimod Followed by Observation | Complete Clearance | 2 participants |
Secondary
Cosmetic Appearance
Change (improvement) in investigator scores of cosmetic appearance of the treatment area (entire face) by objective and subjective assessments: INVESTIGATOR COSMETIC ASSESSMENT 0 - Facial skin is smooth to the touch, without significant lines or unevenness in pigmentation 1 - Facial skin shows 1 area (cheeks, forehead, or the perioral area) of significant 3 - Facial skin shows 3 areas with significant roughness, dyspigmentation, or fine lines 2 - Facial skin shows 2 areas of significant roughness, dyspigmentation, or fine lines 4 - All are severe in severity
Time frame: Week 18 (4 weeks after randomization visit)
Population: Randomized patients with both a baseline and a week 18 investigator cosmetic appearance score. One imiquimod/observation patient did not have an end of study investigator cosmetic appearance score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imiquimod Followed by Photodynamic Therapy | Cosmetic Appearance | 1.67 units on a scale | Standard Deviation 1 |
| Imiquimod Followed by Observation | Cosmetic Appearance | 1.25 units on a scale | Standard Deviation 0.71 |