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 demonstrate that ingenol mebutate gel is efficacious in treating AKs present 8 weeks after initial field treatment (field recalcitrant) or emerging in a previously cleared field (field recurrent).
Efficacy will be evaluated separately for the two sub-groups of “field recalcitrant” and “field recurrent”.
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E.2.2 | Secondary objectives of the trial |
To demonstrate that ingenol mebutate gel repeat use shows a higher complete clearance rate at Month 12 compared with single use of ingenol mebutate gel plus vehicle gel use in patients with multiple AKs on face or scalp.
To evaluate the safety profile of ingenol mebutate gel second use compared with ingenol mebutate gel first use in patients with multiple AKs on face or scalp.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Following verbal and written information about the trial, subject must provide informed consent documented by signing the Informed Consent Form (ICF) prior to any trial-related procedures
2. Subjects with 4 to 8 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, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or,
b. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to study treatment, to rule out pregnancy.
5. Female subjects of childbearing potential must be willing to consent to using highly effective methods of contraception (Pearl index < 1%) at study entry until completion of the Second Treatment Cycle (i.e. 8 weeks after randomisation) or until Week 44 for those subjects not randomised. These methods of contraception are defined as:
• abstinence (when this is in line with the preferred and usual lifestyle of the subject)
• vasectomised partner (partner should be the sole partner for the subject)
• an intrauterine device
• double barrier method defined as two distinct methods (either two actual barrier meth-ods or one actual barrier method and one hormonal method)
• hormonal contraceptive (oral hormonal birth control, estrogenic vaginal ring, percuta-neous contraceptive patches, implants and injectables) for at least one menstrual cycle prior to enrolment (Day 1)
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E.4 | Principal exclusion criteria |
1. Location of the selected treatment area:
• on any location other than the face or scalp
• on the periorbital skin
•within 5 cm of an incompletely healed wound
• within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)
2. Prior treatment with ingenol mebutate gel on face or scalp (previous treatment on trunk and extremities acceptable).
3. Selected treatment area lesions that have atypical clinical appearance.
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 (e.g., eczema, psoriasis).
5. Anticipated need for hospitalization or out-patient surgery prior to Day 15 in the first treatment cycle.
6. Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel.
7. Presence of sunburn within the selected treatment area
8. Current enrolment or participation in a clinical trial within 30 days of entry into this study.
9. Subjects previously entered first treatment in the trial.
10. Female subjects who are breastfeeding.
11. Subjects who are institutionalised by court order or by the local authority
12. 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) |
Complete clearance of AKs, defined as no clinically visible AKs in the selected treatment area, 8 weeks after randomisation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint of evaluation is after completion of the Second Treatment Cycle, corresponding to 8 weeks after randomisation. |
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E.5.2 | Secondary end point(s) |
1. Complete clearance through to Month 12, defined as no clinically visible AKs and no lesions treated in the selected treatment area at any time from last treatment cycle through to Month 12.
2. Change in AK count in the selected treatment area from randomisation to 8 weeks after randomisation.
3. Adverse events occurring within first and second treatment cycles.
4. Change in composite LSR score at Day 4 between first and second ingenol mebutate gel treatment cycles
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint of evaluation:
Regarding 1: Completion of the last treatment cycle at all visits through to Month 12
Regarding 2: At randomisation and at 8 weeks after randomisation
Regarding 3: The period from Day 1 to Day 57 in a Treatment Cycle.
Regarding 4: Day 4 in each Treatment Cycle. |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
The first treatment is opel Label: the second treatment is double blind |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
France |
Germany |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |