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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-005018-13 | EudraCT Number |
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The purpose of the study is to demonstrate that ingenol mebutate gel is efficacious in treating Actinic Keratoses (AKs) present 8 weeks after initial field treatment or emerging in a previously cleared field.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ingenol mebutate gel, 0.015% | Active Comparator | Topical field treatment once daily for 3 consecutive days on the face or scalp |
|
| Vehicle gel | Placebo Comparator | Topical field treatment once daily for 3 consecutive days on the face or scalp |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ingenol mebutate gel, 0.015% | Drug | Topical field treatment once daily for 3 consecutive days within a 25 cm2 treatment area on the face or scalp of AKs present or emerging after an initial treatment with ingenol mebutate gel, 0.015% |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Complete Clearance of AKs 8 Weeks After Randomisation | The complete clearance rates 8 weeks after randomisation was compared between ingenol mebutate gel, 0.015% and vehicle gel. Complete clearance was defined as no clinically visible AKs in the Selected Treatment Area (STA) | 8 weeks after randomisation |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With 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 | The analysis was done separately for the field recalcitrant subgroup, the field recurrent subgroup, and overall for all treated subject (Analysis 1, 2, and 3, respectively) | From last treatment cycle through to Month 12 |
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Inclusion Criteria:
Subjects must provide informed consent
Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous 25 cm2 treatment area on the face or scalp
Subject at least 18 years of age
Female subjects must be of either:
Female subjects of childbearing potential must be willing to consent to using highly effective methods of contraception
Exclusion Criteria:
Location of the selected treatment area:
Prior treatment with ingenol mebutate gel on face or scalp (previous treatment on trunk and extremities acceptable)
Selected treatment area lesions that have atypical clinical appearance
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
Anticipated need for hospitalization or out-patient surgery prior to Day 15 in the first treatment cycle
Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel
Presence of sunburn within the selected treatment area
Current enrollment or participation in a clinical trial within 30 days of entry into this study
Subjects previously entered first treatment in the trial
Female subjects who are breastfeeding
Subjects who are institutionalised by court order or by the local authority
In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol
Prohibited Therapies and/or Medications within 2 weeks prior to Day 1
Prohibited Therapies and/or Medications: within 4 weeks prior to Day 1
Prohibited Therapies and/or Medications within 8 weeks prior to Day 1
Prohibited Therapies and/or Medications within 6 months prior to Day 1
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| Name | Affiliation | Role |
|---|---|---|
| Claus Garbe, MD | University Hospital Tuebingen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St John of God Dermatology | Subiaco | 6008 | Australia | |||
| Stratica Medical |
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| Label | URL |
|---|---|
| Clinical Trials at LEO Pharma | View source |
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A total of 463 subjects were enrolled, 13 of whom were screening failures. 450 subjects were allocated to open label treatment with ingenol mebutate gel (1st cycle) and subsequently administered a 2nd cycle in a randomised vehicle controlled setting, if eligible for repeat use
First Subject First Visit: 04-Jun-2012 Last Subject Last Visit: 05-Feb-2014
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| ID | Title | Description |
|---|---|---|
| FG000 | Ingenol Mebutate Gel, 0.015% (1st & 2nd Cycle) | Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm^2 treatment area on the face or scalp, followed by observation and/or repeat use (2nd cycle) once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area, in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) with follow-up until Week 52 |
| FG001 | Vehicle Gel (2nd Cycle) | Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm^2 treatment area on the face or scalp, followed by observation and/or repeat use (2nd cycle) once daily for 3 consecutive days with vehicle gel of the same treatment area, in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) with follow-up until Week 52 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1. Cycle & Observation Period D1 to W52 |
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| 2. Cycle Recalcitrant Subgroup W8 to W52 |
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| 2. Cycl Recurrent Subgroup W26/44 to W52 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ingenol Mebutate 0.015% Gel (1.& 2. Cycle) | Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm^2 treatment area on the face or scalp, followed by observation and/or controlled repeat use (2nd cycle) treatment of recalcitrant or recurrent AK lesions |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Complete Clearance of AKs 8 Weeks After Randomisation | The complete clearance rates 8 weeks after randomisation was compared between ingenol mebutate gel, 0.015% and vehicle gel. Complete clearance was defined as no clinically visible AKs in the Selected Treatment Area (STA) | Posted | Number | participants | 8 weeks after randomisation |
|
8-week treatment periods (1st or 2nd cycle)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ingenol Mebutate 0.015% Gel (1. Cycle) | Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel within a 25 cm2 treatment area on the face or scalp |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosure Manager | LEO Pharma A/S | +45 44945888 | ctr.disclosure@leo-pharma.com |
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| ID | Term |
|---|---|
| D055623 | Keratosis, Actinic |
| ID | Term |
|---|---|
| D011230 | Precancerous Conditions |
| D009369 | Neoplasms |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
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| Vehicle gel | Drug | Topical field treatment once daily for 3 consecutive days within a 25 cm2 treatment area on the face or scalp of AKs present or emerging after an initial treatment with ingenol mebutate gel, 0.015% |
|
| The Change in AK Count From Randomisation to 8 Weeks After Randomisation | The change in AK count from randomisation to 8 weeks after randomisation was determined for the field recalcitrant and the field recurrent subgroups | 8 weeks after randomisation |
| Edmonton |
| Alberta |
| T5K 1X3 |
| Canada |
| Skin Care Centre | Vancouver | British Columbia | V5Z 4E8 | Canada |
| Dermadvances Research | Winnipeg | Manitoba | R3C 1R4 | Canada |
| Durondel C.P. Inc./Dermatology Clinic | Moncton | New Brunswick | E1C 8X3 | Canada |
| UltraNova Skincare | Barrie | Ontario | L4M 6L2 | Canada |
| SKiN Centre for Dermatology | Peterborough | Ontario | K9J 1Z2 | Canada |
| Windsor Clinical Research Inc. | Windsor | Ontario | N8W 5L7 | Canada |
| Innovaderm Research Inc. | Montreal | Quebec | H2K 4L5 | Canada |
| Centre de Recherche Dermatologique | Québec | Quebec | G1V 4X7 | Canada |
| CHU de Nantes | Nantes | Loire-Atlantique 6 | 44000 | France |
| Universitätsklinikum Tübingen | Tübingen | 72076 | Germany |
| Central Manchester University Hosptial | Manchester | Greater Manchester | M13 9WL | United Kingdom |
| Adverse Event |
|
| Other |
|
| Exclusion Criteria Emerging during Study |
|
| Protocol Violation |
|
| Lost to Follow-up |
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| NOT COMPLETED |
|
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| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Vehicle Gel Field Recalcitrant Subgroup |
Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 8 with follow-up until Week 52 |
| OG002 | Ingenol Mebutate Gel 0.015% Field Recurrent Subgroup | Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52 |
| OG003 | Vehicle Gel Field Recurrent Subgroup | Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52 |
|
|
|
| Secondary | Number of Participants With 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 | The analysis was done separately for the field recalcitrant subgroup, the field recurrent subgroup, and overall for all treated subject (Analysis 1, 2, and 3, respectively) | Posted | Number | participants | From last treatment cycle through to Month 12 |
|
|
|
|
| Secondary | The Change in AK Count From Randomisation to 8 Weeks After Randomisation | The change in AK count from randomisation to 8 weeks after randomisation was determined for the field recalcitrant and the field recurrent subgroups | Posted | Mean | Standard Deviation | AK count | 8 weeks after randomisation |
|
|
|
|
| 7 |
| 450 |
| 197 |
| 450 |
| EG001 | Ingenol Mebutate 0.015% Gel (2. Cycle) | Repeat use once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (25 cm2 treatment area on the face or scalp) in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) | 1 | 134 | 61 | 134 |
| EG002 | Vehicle Gel (2. Cycle) | Repeat use once daily for 3 consecutive days with vehicle gel of the same treatment area (25 cm2 treatment area on the face or scalp) in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) | 3 | 69 | 19 | 69 |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Myocardial infarction | Cardiac disorders | MedDRA (15.1) |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (15.1) |
|
| Prostatism | Reproductive system and breast disorders | MedDRA (15.1) |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) |
|
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) |
|
| Headache | Nervous system disorders | MedDRA (15.1) |
|
| Eyelid oedema | Eye disorders | MedDRA (15.1) |
|
| Periorbital oedema | Eye disorders | MedDRA (15.1) |
|
| Application site pain | General disorders | MedDRA (15.1) |
|
| Application site pruritus | General disorders | MedDRA (15.1) |
|
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA (15.1) |
|
| Nasopharyngitis | Infections and infestations | MedDRA (15.1) |
|
| Oral herpes | Infections and infestations | MedDRA (15.1) |
|
LEO acknowledges the investigators right to publish the entire results of the study, irrespective of outcome. LEO retains the right to have any publication submitted to LEO for review. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO.
| D017437 |
| Skin and Connective Tissue Diseases |
| The analysis type was superiority between groups. In total 62 subjects were included | Cochran-Mantel-Haenszel | Cochran-Mantel-Haenszel ratio of clearance rates (Ingenol mebutate relative to Vehicle) adjusted for anatomical location and country | 0.10 | A closed test procedure was chosen where the evaluation process stopped when the first non-significant results were observed thus securing that the overall significance level did not exceed 5% for multiple testing | Risk Ratio (RR) | 2.24 | 2-Sided | 95 | 0.78 | 6.47 | Superiority or Other (legacy) |
| Subjects randomised to vehicle were not included in the estimate of the overall clearance rate for the repeat-use regimen, from last treatment throught to Month 12. Instead, the subjects randomised to ingenol mebutate were given higher weights to reflect the hypothetical scenario where all randomised subjects were given active treatment during the repeat use cycle | Percent cleared subjects | 50.0 | 2-Sided | 95 | 44.0 | 56.1 | Estimation based on completers only. | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| The analysis type was superiority between groups. In total 141 subjects were included | ANCOVA | Sensitivity analysis using complete cases | <0.001 | A closed test procedure was chosen where the evaluation process stopped when the first non-significant results were observed thus securing that the overall significance level did not exceed 5% for multiple testing | Mean Difference (Net) | -1.01 | 2-Sided | 95 | -1.52 | -0.51 | Sensitivity analysis using complete cases | Superiority or Other (legacy) |
| The analysis type was superiority between groups. In total 62 subjects were included | ANCOVA | Analysed using ANCOVA adjusted for anatomical location, country and AK count at randomisation | 0.008 | Formal statistical significance could not be established because of the closed test procedure where the first secondary endpoint tested (12 months clearance) did not reach statistical significance in the recurrent subgroup | Mean Difference (Net) | -0.69 | 2-Sided | 95 | -1.19 | -0.19 | Using BOCF as the imputation method, the difference in the adjusted mean AK count between the ingenol mebutate and vehicle groups | Superiority or Other (legacy) |