Actinic Keratoses
Conditions
Keywords
Actinic Keratoses
Brief summary
In this study the impact of Oleogel-S-10 versus placebo on actinic keratoses over a treatment period of 3 months will be tested. Additionally, once and twice daily applications are tested.
Detailed description
Oleogel-S-10 has shown efficacy and was well tolerated in two previous clinical trials. In the second open label phase II trial the efficacy of Oleogel-S-10 alone was similar compared to a more invasive treatment with cryotherapy. Response rates of 85% with a clear-ance of more than 75 % of the lesions of the patients treated with Oleogel-S-10 over three months were reported. These encouraging results led to the present randomized, multicenter, double blind phase II trial. The efficacy of the treatment shall be tested in a double blind placebo controlled (petroleum jelly) fashion in order to obtain more reliable results for the planning of a phase III study.
Interventions
DRUGOleogel-S10 100 mg/g
topical use once or twice daily
DRUGPlacebo (petroleum jelly)
topical use once or twice daily
Sponsors
University Hospital Tuebingen
Birken AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least two mild to moderate actinic keratoses located at the facial skin or the head (except lips) * Actinic keratoses with a diameter of 0,5 - 2 cm, * that are definitely distinguished from other lesions and display a minimum distance of 0,5 cm to neighbored lesions * that are evaluated as histopathological grade 1 to 3 * histologically proven AK within three months before study entry * prepared and able to give written informed consent * ≥ 18 years of age * In case of females: postmenopause defined as * natural menopause with menses \> 1 year ago * serum FSH (\> 20 IU/l) and E2 levels in the postmenopausal range or * patients who had bilateral oophorectomy * prepared and comply with all study requirements, including the following: * application of Oleogel-S10 on the treatment area once or twice a day * 4 clinic visits during the pre-study, treatment, post-treatment, and follow-up period * pre- and post-treatment biopsy for histological confirmation (of clearance) of AK-diagnosis * Representative histologic slide and tissue block were shipped
Exclusion criteria
* Active immunosuppressive therapy * data of clinically significant, unstable, cardiovascular or hematologic, hepatic, neurologic, renal, endocrine, collagen-vascular, or gastrointestinal abnormalities or diseases Note: Patients with clinically stable medical conditions including, but not limited to, controlled hypertension, diabetes mellitus type II, hypercholesterolemia, or osteoarthritis will be allowed to enter the study * known allergies to any excipient in the study drug * any dermatological disease and/or condition in the treatment or surrounding area (3 cm distances from treatment area) that may be exacerbated by treatment with Oleogel-S-10 or cause difficulty with examination * active chemical dependency or alcoholism, as assessed by the investigator * pregnant and lactating women * currently participating in another clinical study or have completed another clinical study with an investigational drug within the past 30 days * received topical treatment at the treatment area with diclofenac gel, imiquimod or 5-FU within a time period of 1 month * Concomitant existence of non-treated (non-excised) basal cell carcinoma, squamous cell carcinoma or malignant melanoma * Invasive tumors within the treatment area, e.g.: merkel cell carcinoma, squamous cell carcinoma, basal cell carcinoma, the latter is accepted if completely surgically removed Note: A biopsy of any lesion within the treatment or surrounding area suggestive of malignancy should be performed at the pre-study screening visit. If invasive SCC or other malignant conditions are confirmed within the treatment area, the patient will not be included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance. | 18 weeks | Objective response of the marker actinic keratosis, defined as histologically complete or partial clearance (partial clearance = down-grading in Cockerell-classification). The marker actinic keratosis is defined as an initially selected lesion within the target area that will be used for final biopsy. The Cockerell classification refers to a single lesion, graded as the presence of atypical cells in the lower third of the epidermis (grade I), involvement of at least the lower two-thirds (grade II) or atypical keratinocytic proliferation in the entire epidermis (grade III). Thus a down-grading from a higher Cockerell grade (e.g., III) to a lower Cockerell grade (e.g., I) represents a positive outcome and treatment success. |
Countries
Germany, Greece
Participant flow
Recruitment details
165 patients were recruited.
Pre-assignment details
157 patients were evaluated in the ITT population. 8 of 165 recruited patients were excluded from ITT evaluation due to a deviation from the inclusion and exclusion criteria. For safety evaluations, all 165 patients had received treatment with study medication and all 165 patients were assessed for adverse events.
Participants by arm
| Arm | Count |
|---|---|
| A - Oleogel-S10 Once Daily Oleogel-S10 ointment for three months once a day (54 patients)
Oleogel-S10: topical use once or twice daily | 53 |
| B - Oleogel-S10 Twice Daily Oleogel-S10 vehicle for three months twice a day (54 patients)
Oleogel-S10: topical use once or twice daily | 51 |
| C - Placebo Once Daily Placebo (petroleum jelly) for three months once a day (27 patients)
Placebo (petroleum jelly) | 25 |
| D - Placebo Twice Daily Placebo (petroleum jelly) for three months twice a day (27 patients)
Placebo (petroleum jelly) | 28 |
| Total | 157 |
Baseline characteristics
| Characteristic | A - Oleogel-S10 Once Daily | Total | D - Placebo Twice Daily | C - Placebo Once Daily | B - Oleogel-S10 Twice Daily |
|---|---|---|---|---|---|
| Actinic keratosis baseline severity index Mild | 22 participants | 62 participants | 13 participants | 9 participants | 18 participants |
| Actinic keratosis baseline severity index Moderate | 31 participants | 95 participants | 15 participants | 16 participants | 33 participants |
| Age, Continuous | 72 years | 72 years | 72 years | 69 years | 74 years |
| Histopathological grading Grade I | 9 participants | 17 participants | 2 participants | 2 participants | 4 participants |
| Histopathological grading Grade II | 11 participants | 37 participants | 12 participants | 4 participants | 10 participants |
| Histopathological grading Grade III | 32 participants | 100 participants | 13 participants | 19 participants | 36 participants |
| Histopathological grading not done | 1 participants | 3 participants | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 41 Participants | 128 Participants | 25 Participants | 20 Participants | 42 Participants |
| Sex: Female, Male Male | 12 Participants | 29 Participants | 3 Participants | 5 Participants | 9 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 57 | 7 / 54 | 3 / 26 | 3 / 28 |
| serious Total, serious adverse events | 2 / 57 | 3 / 54 | 0 / 26 | 0 / 28 |
Outcome results
Primary
Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance.
Objective response of the marker actinic keratosis, defined as histologically complete or partial clearance (partial clearance = down-grading in Cockerell-classification). The marker actinic keratosis is defined as an initially selected lesion within the target area that will be used for final biopsy. The Cockerell classification refers to a single lesion, graded as the presence of atypical cells in the lower third of the epidermis (grade I), involvement of at least the lower two-thirds (grade II) or atypical keratinocytic proliferation in the entire epidermis (grade III). Thus a down-grading from a higher Cockerell grade (e.g., III) to a lower Cockerell grade (e.g., I) represents a positive outcome and treatment success.
Time frame: 18 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A - Oleogel-S10 Once Daily | Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance. | Success: Downgrading or clearance | 22 participants |
| A - Oleogel-S10 Once Daily | Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance. | Failure: No downgrading or clearance | 25 participants |
| B - Oleogel-S10 Twice Daily | Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance. | Success: Downgrading or clearance | 17 participants |
| B - Oleogel-S10 Twice Daily | Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance. | Failure: No downgrading or clearance | 22 participants |
| C/D - Placebo Once or Twice Daily | Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance. | Success: Downgrading or clearance | 19 participants |
| C/D - Placebo Once or Twice Daily | Objective Response of the Marker Actinic Keratosis, Defined as Histologically Complete or Partial Clearance. | Failure: No downgrading or clearance | 27 participants |
Comparison: A vs C/Dp-value: 0.6Mantel Haenszel
Comparison: B vs. C/Dp-value: 0.83Mantel Haenszel