E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Actinic keratosis on the face and scalp |
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E.1.1.1 | Medical condition in easily understood language |
Actinic keratosis 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 |
To compare the cumulative incidence of squamous cell carcinoma (SCC) after treatment with ingenol mebutate gel and imiquimod cream. |
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E.2.2 | Secondary objectives of the trial |
To compare the cumulative incidence of neoplasia and the short-term and 12-month efficacy of ingenol mebutate gel with imiquimod cream. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Signed Informed Consent Form (ICF) prior to any trial-related procedures
2.Subjects with 5 to 9 clinically typical, visible and discrete AKs within a contiguous 25 cm² treatment area on the face or scalp.
3.Subject at least 18 years of age
4.Female subjects must be of either:
a.Non-childbearing potential, or,
b.Childbearing potential, provided there is a confirmed negative urine pregnancy test
5.Female subjects of childbearing potential must be willing to use highly effective methods of contraception (Pearl index < 1%)
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E.4 | Principal exclusion criteria |
1.Location of the selected treatment area:
•on the periorbital skin
•on the perioral skin/around the nostrils
•within 5 cm of an incompletely healed wound
•within 10 cm of a suspected BCC or SCC or other neoplasia
2.Selected treatment area lesions that have atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horn).
3.History of SCC, BCC, malignant melanoma or other neoplasia in the selected treatment area.
4.History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the trial medication in the selected treatment area
5.Use of ingenol mebutate and/or imiquimod in and within 5 cm of the selected treatment area within 2 years prior to Screening (Visit 1)
6.Organ transplant recipients
7.Immunosuppressed subjects (for example HIV patients)
8.Female subjects who are breastfeeding.
9.Subjects who are institutionalised by court order or by the local authority
10.In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Diagnosis of SCC (defined as invasive SCC i.e. excludes SCC in situ) in the treatment field across the 3-year trial period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Completion of the 3 year trial period. |
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E.5.2 | Secondary end point(s) |
1.Diagnosis of SCC and other neoplasia in the treatment field over a 3-year period.
2.Complete clearance after the last treatment cycle (at Week 8 or 16)
3.Partial (at least 75%) clearance after the last treatment cycle (at Week 8 or 16)
4.Complete clearance at 12 months, defined as no AKs in the selected treatment area at any time from the last treatment cycle at Week 8 or 16 through to Month 12.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint of evaluation:
Regarding 1: Completion of the 3 year trial period.
Regarding 2: Completion of the last treatment cycle (week 8 or 16)
Regarding 3: Completion of the last treatment cycle (week8 or 16)
Regarding 4: At 12 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 | |
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 |