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 is to determine the long-term outcome with respect to the risk of progression to SCC (in situ and/or invasive) of
treatment with Aldara® 5% cream (IMIQ) and Solaraze® 3% gel (DIC) with increased precision (meta-analysis with study X-03016-3271). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include recurrence rates, the time to recurrence, need of rescue treatment, and cosmetic outcome. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Immunocompetent patient.
2. A study treatment area 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 (see Section 7.1.1.2). 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 |
1. History of hypersensitivity 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 excessive hyperkeratosis 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. 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.
7. Any dermatological disease or condition that may exacerbate by treatment with
imiquimod or diclofenac (e.g. rosacea, psoriasis, atopic dermatitis).
8. Any dermatological disease or condition in the STA that causes difficulty with
examination (e.g. eczema).
9. 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.
10. History of any malignant tumour with high tumour burden or any systemic antitumour
treatment (incl. radiotherapy).
11. History of any malignant skin tumour having metastasised or in which metastasis within
the study period is likely.
12. History of severe cardiovascular, pulmonary, hepatic, renal, gastrointestinal,
haematological, endocrine, metabolic, mental, neurological, or other disease within the
last two years which might hinder regular treatment and supervision and might lead to
premature withdrawal from the study.
13. Mentally incapacitated patient.
14. Present or history of drug or alcohol abuse within the last 3 years.
Administrative reasons:
15. Exposure to an investigational product within the last 3 months.
16. Lack of ability or willingness to give informed consent.
17. Age below 18 years.
18. Lack of willingness to have personal study related data collected, archived or transmitted
according to protocol.
19. Anticipated non-availability for study visits/procedures.
20. Vulnerable subjects (such as persons kept in detention). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The histological finding of an in situ SCC or an invasive SCC after start of treatment will be considered as "histological progression", which is the primary efficacy variable ("endpoint"). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
20 weeks after start of each treatment cycle until month 36. |
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E.5.2 | Secondary end point(s) |
2) Histological classification.
3) Recurrence with respect to the study treatment area. A patient is classified as recurrent when cleared at Visit Week 20 and having later on at least one clinically diagnosed AK lesion in the STA.
4) Incidence of withdrawals from study treatment due to lack of efficacy.
5) Percent clinical clearance (complete = 100%, partial = 75%, and individual clearance) of baseline AK lesions in the study treatment area 8 weeks after end of treatment and at Week 20.
6) Lesion clearance 8 weeks after end of treatment and at Week 20.
7) Number of treatment cycles per patient in the STA during the study.
8) Number of patients with cryotherapy in the STA during the study.
9) Number of cryotherapies in the STA by patient.
10) Total number of lesions treated with cryotherapy in the STA during
the study.
11) Cosmetic outcome (investigator and patient) at Week 20 and then at
Month 12, 18, 24, 30 and 36.
12) Local skin reactions.
13) Adverse events of special interest.
14) Other adverse events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2) 20 weeks after start of each treatment cycle until month 36.
3,7) at least half-yearly until m36.
4,8,9,10) at any visit until m36.
5,6) 8 weeks after end of treatment and at Week 20.
11) at Week 20 and then at at least half-yearly until m36.
12,13,14) at each visit until m36. |
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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 | 20 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |