E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Actinic keratosis is a lesion of the skin that may develop into a type of skin cancer. |
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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 | 18.1 |
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 assess tolerability and safety of topical LFX453 formulations in patients with actinic keratosis (AK)
• To assess efficacy of topical LFX453 formulations in treating AK compared to vehicle after 2 cycles of 4 week treatment. |
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E.2.2 | Secondary objectives of the trial |
• To determine the pharmacokinetics of topical LFX453 formulations
• To assess efficacy of LFX453 in treating AK compared to vehicle at week 8 and week 16 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent must be obtained before any assessment is performed.
• Male patients, and female patients of non-childbearing potential, age ≥ 18 to ≤ 75 years (at the time of the screening visit), and in general good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• Patients with at least five (5) clinically typical, visible or palpable non-hyperkeratotic AK lesions within a contiguous area of 25 cm2, or within 2 areas for a maximum total of 25cm2, on the face (at least 2 cm from the periocular areas, lips, nares and excluding ears) and/or balding scalp.
• Presence of at least one additional visible or palpable non hyperkeratotic AK lesion outside of the selected treatment area amenable to the collection of a skin biopsy, and located at least 2 cm from the limits of the area to receive treatment |
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E.4 | Principal exclusion criteria |
• Known hypersensitivity to any constituents of the study drugs (including local anesthetics) or known allergies to imiquimod or to drugs of similar chemical classes or history of serious allergic reaction.
• Presence of atopic dermatitis, eczema, psoriasis, rosacea or other possible confounding skin conditions on the face or balding scalp, even outside of the treatment area.
• Invasive tumors within the treatment area, e.g., merkel cell carcinoma, melanoma, squamous cell carcinoma (SCC), basal cell carcinoma, the latter being 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.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or Bowen’s disease or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Concurrent disease that suppresses the immune system. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- All safety endpoints (including physical exam, vital signs, ECG, safety laboratory)
- Number and type of (serious) adverse events
- Local tolerability assessment scores compared to baseline
- Proportion of patients achieving total clearance of AK 8 weeks after end of treatment
- Reduction from baseline of AK lesion count in treated area 8 weeks after end of treatment
- Proportion of patients achieving partial clearance of at least 75% of lesions after 8 weeks follow-up |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Concentrations of LFX453 measured in skin and plasma samples
- Reduction from baseline in AK lesion count in treated area at 4 weeks after end of first treatment cycle (week 8)
- Proportion of patients achieving total clearance of AK at 4 weeks after end of first treatment cycle (week 8) and at 4 weeks after end of second treatment cycle (week 16)
- Proportion of patients achieving partial clearance of at least 75% of lesions at week 8 and week 16 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |