E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study will compare the long term effects of Aldara® and Solaraze® of the actinic keratoses on the face or scalp. Actinic keratoses (AKs) are defined as keratotic macules, papules or plaques with superficial scale on a red base, occurring on areas of extensive damage through sunlight. AKs are mainly induced by non-ionised radiation, especially through chronic UV-exposition, primarily sunlight. |
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E.1.1.1 | Medical condition in easily understood language |
The study will compare the long term effects of Aldara® and Solaraze® of the skin disease actinic keratosis (spot-like scaly papules) on the face and scalp. |
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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 |
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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 primary objective of the study is to compare the long-term outcome of treatment with Aldara® 5% cream (IMIQ) and Solaraze® 3% gel (DIC) regarding recurrence rates. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include the time to recurrence, long-term outcome with respect to development of invasive SCC (squamous cell carcinoma) (in situ and/or invasive), need of rescue treatment, haematological changes, and cosmetic outcome. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible, a patient must comply with all of the following criteria:
1. Immunocompetent patient.
2. A study treatment area (STA) must be identifiable: Minimum of 5 and maximum of 10 typical visible AKs in one contiguous area of up to 50 cm2 on the face or scalp. The eyelids, the inside of the nostrils or ears, or the lip area inside the vermilion border must not be part of this area.
3. A positive histological finding for AK grade I or II. This will be
determined from the most suspicious lesion in the STA and there from the most pathological area biopsied during screening visit. This analysis will be done by the central histopathological laboratory.
4. Willingness to comply with the obligations of the study |
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E.4 | Principal exclusion criteria |
A patient is ineligible and must not enter the study if any of the following
criteria is met:
Safety concerns:
1. History of allergic reaction to imiquimod, diclofenac, acetyl salicylic acid, other non-steroidal anti-inflammatory drugs (NSAID), hyaluronic acid, or relevant excipients.
2. Pregnancy, breast-feeding or planned pregnancy during the study. Women of child bearing potential not using a highly effective method of birth control defined as those which result in a low failure rate (i.e. <1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, tubal ligation or vasectomised partner.
Lack of suitability for the study:
3. Presence of AK lesions in the STA with clinically marked
hyperkeratosis or hypertrophy as seen in cutaneous horns.
4. Any topical AK treatment including imiquimod or diclofenac, or any systemic AK treatment such as systemic retinoids, or any surgical AK treatment at the STA within the last 2 months prior to randomisation.
5. Persisting AK lesion at screening visit following topical treatment with imiquimod or diclofenac in the STA .
6. Topical treatment with imiquimod or diclofenac anywhere else on the body within the last 2 months prior to randomisation.
7. Presence of any histologically confirmed skin tumour in the STA: in situ SCC including Bowen's disease, invasive SCC, basal cell carcinoma or other malignant tumours.
8. Any dermatological disease or condition that may exacerbate by treatment with imiquimod or diclofenac (e.g. rosacea, psoriasis, atopic dermatitis).
9. Any dermatological disease or condition in the STA that causes
difficulty with examination (e.g. eczema).
10. Systemic immunomodulatory treatment such as interferon,
azathioprine, cyclosporine, retinoids, any oral or injectable
corticosteroids, or inhaled or nasal corticosteroids with dosages of >1200 μg/day beclomethasone or equivalent within 4 weeks before start of study treatment.
11. History of any malignant tumour with high tumour burden or any systemic antitumour treatment (incl. radiotherapy).
12. History of any malignant skin tumour having metastasised or where metastasis could be expected.
13. History of severe cardiovascular, pulmonary, hepatic, renal,
gastrointestinal, haematological, endocrine, metabolic, mental,
neurological, or other disease within the last two years.
14. Mentally incapacitated patient.
15. Present or history of drug or alcohol abuse within the last 3 years.
Administrative reasons:
16. Exposure to an investigational product within the last 3 months.
17. Lack of ability or willingness to give informed consent.
18. Age below 18 years.
19. Lack of willingness to have personal study related data collected, archived or transmitted according to protocol.
20. Anticipated non-availability for study visits/procedures.
21. Vulnerable subjects (such as persons kept in detention). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable ("endpoint") is the (patient) recurrence rate with respect to the STA. A patient is classified as recurrent when cleared at Week 20 and having later on at least one clinically diagnosed AK lesion in the STA. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
20 weeks after start of treatment cycle until month 12. |
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E.5.2 | Secondary end point(s) |
Include the time to recurrence, long-term outcome with respect to
development of SCC (in situ and/or invasive), need of rescue treatment, haematological changes, and cosmetic outcome, and adverse events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Depending on the endpoint either 20 weeks after start of each treatment cycle, at least half-yearly or at any visit until month 36. |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |