E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
5-20 clinically confirmed, palpable or visible (grade I or II according to modified Olsen score), nonhyperkeratotic, nonhypertrophic, AK lesions located within a contiguous (25 - 100 cm²) area on the balding scalp or face |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000614 |
E.1.2 | Term | Actinic keratosis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to assess efficacy and safety of different dosing regimens (once, three or seven times weekly) of Limtop in adults with actinic keratosis (AK) on the head (balding scalp or face). |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent form (ICF) signed and dated by the patient prior to any study-related activity
2. Male or female patients aged 18 or older
3. Have a total of 5-20 clinically confirmed, palpable or visible (grade I or II according to modified Olsen score) nonhyperkeratotic, nonhypertrophic AK lesions located within a contiguous 25 – 100 cm² area on the balding scalp or face
4. Any skin type or race, providing the skin pigmentation will allow discernment of erythema
5. Willingness to actively participate in the study and to comply with the study procedures as defined in the study protocol
6. High probability of a good compliance and orderly completion of the study
7. Negative urine pregnancy test (in female subjects with childbearing potential)
|
|
E.4 | Principal exclusion criteria |
1. Evidence of clinically significant, unstable cardiovascular or immunosuppressive, hematologic, hepatic, neurologic, renal, endocrine, collagen-vascular, or gastrointestinal abnormalities or disease
2. Diagnosed autoimmune diseases and anaemia
3. Any dermatological disease and or condition in the treatment or surrounding area that may be exacerbated by treatment with imiquimod or cause difficulty with examination (e.g. rosacea, psoriasis, atopic dermatitis, eczema)
4. Any significant findings (e.g. tattoos) in the potential application site area that may impair examination of treatment or surrounding area
5. Confirmed squamous cell or basal cell carcinoma anywhere on the head in the past 3 months
6. Share a household where there is a person participating in a concurrent clinical study of imiquimod or being treated with imiquimod 5% topical cream
7. Active chemical dependency or alcoholism, as assessed by investigator
8. Patients unwilling to stay out of the sun or wear protective clothing or to take appropriate measures to cover the treatment area during the study
9. Previous treatments with imiquimod for AK in the predetermined treatment area within the past 3 months
10. Treatment with COX-2 inhibitors 14 days prior to randomization
11. Currently using or have used on the treatment area over-the-counter retinol products, corticosteroids, cryosurgery, curettage, 5-fluorouracil, or other topical actinic keratosis treatments 28 days prior to randomization
12. Subjects who experienced an unsuccessful outcome from previous imiquimod therapy.
13. Known allergy or sensitivity to imiquimod or any of the excipients (butyl lactate, isopropyl myristate, propylene glycol, butylated hydroxy anisole) in the IMP
14. Pre-menopausal (last menstruation ≤ 1 year prior to screening) sexually active women who:
• are pregnant or nursing,
• are not surgically sterile,
• are of child bearing potential and not practicing an acceptable method of birth control, or does not plan to continue practicing an acceptable method of birth control throughout the trial (acceptable methods include intrauterine devices (IUD), oral, implantable or injectable contraceptives, diaphragm or cervical cap with intravaginal spermicide, condom with intravaginal spermicide or vasectomised partner)
15. Participation in another clincial trial with an investigational drug or device during the previous 4 weeks before Baseline
16. Receiving systemic cancer chemotherapy, psoralen plus UVA therapy, UVB therapy, laser abrasion, dermabrasion, glycolic acids, or chemical peels 6 months prior to study entry.
17. Currently using or have used systemic steroids 2 months prior to study except inhaled corticosteroids (<1200 g/day for beclomethasone, or <600 g/day for fluticasone)
18. Known infectious diseases (e.g. HIV, hepatitis)
19. Psychiatric condition that might limit the participation in the study and/or that lead to the assumption that the ability to completely understand the consequences of consent is missing
20. Employee of the study site or of the Sponsor’s company
21. Any disease or circumstances on account of which the subject should not participate in the study in the opinion of the investigator
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is defined as the absolute number of target AK lesions in the treatment area at V8 minus the absolute number of target AK lesions at Baseline (V1), divided by the number of target AK lesions at Baseline. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of study = 12 weeks after end of last treatment course |
|
E.5.2 | Secondary end point(s) |
• Percentage change of target lesions during the study defined as the absolute number of target AK lesions in the treatment area at a given visit minus the absolute number of target AK lesions at Baseline, divided by the number of target AK lesions at Baseline.
• Percentage change in overall lesion count during the study defined as the absolute number of AK lesions in the treatment area at a given visit minus the absolute number of all AK lesions at Baseline, divided by the number of all AK lesions at Baseline.
• Percentage change of non-target lesions during the study defined as the absolute number of non-target AK lesions in the treatment area at a given visit minus the absolute number of non-target AK lesions at Baseline, divided by the number of non-target AK lesions at Baseline.
• AK severity score will be assessed as none, mild, moderate or severe at Visit 4, 7 and 8.
• Existence or absence of 9 defined criteria for each subclinical lesion in treatment area assessed at Visit 4 and 8. This efficacy variable will be assessed in a subpopulation of patients (patients at site of Prof. Stockfleth)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
time points of evaluation are:
V4 = 4 weeks after end of first treatment course
V7 = 4 weeks after end of second treatment course
V8 = 12 weeks after end of second treatment course |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
determination of Imiquimod concentration in the blood after 2 weeks of treatment |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |