E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild and/or moderate Actinic Keratoses |
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E.1.1.1 | Medical condition in easily understood language |
Actinic (solar) keratosis |
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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 | 16.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10020648 |
E.1.2 | Term | Hyperkeratoses |
E.1.2 | System Organ Class | 100000004858 |
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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 |
Primary efficacy objective:
To show the non-inferior efficacy of Metvix® Natural Day Light Photo Dynamic Therapy (NDL-PDT) versus Metvix® conventional Photo Dynamic Therapy (c-PDT) in Subjects with mild and moderate AKs at Week 12 in terms of percent reduction in lesions count.
Primary safety objective:
To compare the Subject’s self-assessment of pain of Metvix® NDL-PDT with that of Metvix® c-PDT.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, who is at least 18 years of age or older,
- Clinical diagnosis of mild (Grade 1) and/or moderate (Grade 2) AKs on the face or the scalp on treated areas (TAs) according to Olsen et al scale (1991). (e.g.: thin and/or non-hyperkeratotic AKs),
- Subject with two symmetrical TAs (either two half scalps or two half faces excluding ears, chin, bridge of the nose, eyelids and lips inside the vermillion border): no more than a twofold difference in terms of total number of lesions between the two TAs
- TA comparable in terms of size: 6 by 16 cm at a maximum
- A minimum of 5 AKs (either mild, moderate or both) per TA
- No more than two lesions difference in number of moderate AKs between the two TAs.
- Female of non-childbearing potential, OR female of childbearing potential with a negative urine pregnancy test (UPT).
- If female of childbearing potential, they should:
- have been strictly abstinent 1 month prior to Baseline and agrees to remain abstinent for the duration of the clinical trial,
- and/or agree to use a highly effective and approved contraceptive method(s) during the duration of the clinical trial (bilateral tubal ligation OR combined oral contraceptives (oestrogens and progesterone) or implanted or injectable contraceptives with a stable dose for at least 1 month prior to Baseline OR vasectomized partner for at least 3 months prior to Baseline OR hormonal intra uterine device (IUD) inserted at least 1 month prior to Baseline.
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E.4 | Principal exclusion criteria |
- Subject with clinical diagnosis of at least one severe (Grade 3) AK on TAs according to Olsen et al (1991) scale (e.g. hyperkeratotic AKs),
- Subject with pigmented AK on the TAs,
- Immuno-compromised Subject for idiopathic, disease specific or therapeutic reasons;
- Subject with porphyria,
- Subject with clinical diagnosis of other skin disease (including non-melanoma skin cancer) on the TAs which, in the opinion of the investigator, might interfere with the interpretation of the clinical results,
- Subject with systemic diseases that, in the opinion of the investigator might interfere with the interpretation of the clinical results,
- History of hypersensitivity to nut products (e.g. peanut and almond oil) or soya,
- Subject with a known past history of skin cancer in the TAs
- Past history of skin melanoma
- The Subject has received, applied or taken the following treatments or Procedures within the specified time frame prior to the Baseline visit:
Topical treatment(s) on TAs:
5-Fluorouracil, diclofenac, imiquimod, retinoids, ingenol mebutat (Pep-005) : Duration 12 weeks
Surgical: elliptical excision, excision and reconstructive surgery, Mohs’ micrographic surgery, chemical peels/chemosurgery, cryosurgery, dermabrasion: Duration 12 weeks
PDT: Duration 12 weeks
Laser: Duration 12 weeks
Electrocoagulation: Duration 12 weeks
Radiotherapy and UV radiation therapy: Duration 12 weeks
Investigative therapies for Actinic Keratoses: Duration 12 weeks
Alpha-hydroxy acid, salicylic acid ointment, urea: Duration 2 weeks
Systemic treatment(s)
Systemic retinoids: Duration 12 weeks
Immunosuppressive drugs (such as glucocorticoids, cytostatic, antibodies, drugs acting on immunophilins, interferon, opioids , TNF binding proteins, Mycophenolate, small biologics agents):Duration 12 weeks
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint(s)
The primary efficacy endpoint is the lesion complete response rate, defined as the percentage of pre-existing and treated lesions at baseline that were assessed as clear at Week 12.
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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) |
Secondary efficacy endpoint(s)
- Lesion complete response rate for mild lesions only.
- Subject-side complete response rate defined as the percentage of subjects with all treated lesions clear in the corresponding TA, at Week 12.
- change in lesion severity
- number of new lesion
Primary Safety endpoint
- subject's self assessment of pain at baseline post-PDT procedures
Secondary Safety endpoint
- Incidence and severity of Adverse Events
- skin aspect of lesion in complete response
Other endpoint: weather and light asessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoint(s): at week 12
Safety primary endpoint: at Baseline post PDT-procedure
Secondary safety endpoint:
- adverse event: all along the study
- skin aspect at week 12 |
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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 | 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) | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Intraindividual comparison |
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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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |