Actinic Keratosis, Squamous Cell Carcinoma
Conditions
Brief summary
One of the main reasons for treating actinic keratoses (AK) is the wish to lower the risk of progression of AK to squamous cell carcinoma (SCC). This risk is in the order of 1 per 1000 AKs per year, which is in itself a small risk, but since patients can have dozens of AKs and the disease is chronic the cumulative risk for a patient can be substantial. In this extension protocol of trials LP0084-1193, -1194, -1195 and -1196, LEO will study the incidence of SCCs and other skin neoplasia in vehicle and ingenol disoxate treated patients over a period of 2 years, so that the total follow-up time for each patient will be 3 years and 2 months.
Interventions
DRUGingenol disoxate gel 0.018%
Ingenol disoxate gel is a novel ingenol derivative being developed for field treatment of AKs on treatment areas of up to 250 cm2 (40 in2) on the face, chest and scalp.
DRUGingenol disoxate gel 0.037%
Ingenol disoxate gel is a novel ingenol derivative being developed for field treatment of AKs on treatment areas of up to 250 cm2 (40 in2) on the face, chest and scalp.
OTHERVehicle gel
Vehicle to ingenol disoxate gel with no active ingredient
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent has been obtained. * The subject has been treated in one of the trials LP0084-1193, -1194, -1195, or -1196 and has been evaluated at the end of follow-up visit (month 14) of that trial.
Exclusion criteria
* The subject is in need of treatment with ingenol mebutate or ingenol disoxate in the selected treatment area . * The subject is enrolled in any other interventional clinical trial. For subjects where there is a gap between end of follow-up visit (month 14) in one of the trials LP0084-1193, -1194, -1195, or -1196 and participation in the current trial: * The subject has been treated with ingenol mebutate or ingenol disoxate in the selected treatment area after end of follow-up visit (month 14) in one of the trials LP0084-1193, -1194, -1195, or -1196 and until participation in the current trial. * The subject has been enrolled in any other interventional clinical trial after end of follow-up visit (month 14) in one of the trials LP0084-1193, -1194, -1195, or -1196 and until participation in the current trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Squamous Cell Carcinoma (SCC) in the Treatment Area | From Visit 2 (6 months after Month 14 of main trial) to first SCC in the treatment area, up to 24 months | Time to first squamous cell carcinoma (SCC) in the treatment area. Relative difference between groups (ingenol disoxate vs vehicle) expressed as hazard ratio. The indicated measured values are the observed incidence rates of the SCC in the treatment area which form the basis of the statistical analysis of the time to event analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Squamous Cell Carcinoma (SCC) or Other Skin Neoplasia in the Treatment Area | From Visit 2 (6 months after Month 14 of main trial) to first SCC or other skin neoplasia in the treatment area, up to 24 months | Time to first squamous cell carcinoma (SCC) or other skin neoplasia in the treatment area. Relative difference between groups (ingenol disoxate vs vehicle) expressed as hazard ratio. The indicated measured values are the observed incidence rates of the SCC in the treatment area which form the basis of the statistical analysis of the time to event analysis |
Countries
Canada, France, Germany, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
1234 participants were randomised and applied investigational medicinal product (IMP) in the trials LP0084-1193, -1194, -1195, -1196 (main trials, Period 1). A total of 563 participants from the main trials continued and were enrolled into this extension follow-up trial (LP0084-1369, Period 2).
Participants by arm
| Arm | Count |
|---|---|
| Ingenol Disoxate Gel 0.018% ingenol disoxate gel 0.018%: Ingenol disoxate gel is a novel ingenol derivative being developed for field treatment of AKs on treatment areas of up to 250 cm2 (40 in2) on the face, chest and scalp. | 191 |
| Ingenol Disoxate Gel 0.037% ingenol disoxate gel 0.037%: Ingenol disoxate gel is a novel ingenol derivative being developed for field treatment of AKs on treatment areas of up to 250 cm2 (40 in2) on the face, chest and scalp. | 210 |
| Vehicle Gel Vehicle gel of ingenol disoxate gel | 162 |
| Total | 563 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| LP0084-1369 | Death | 1 | 0 | 2 |
| LP0084-1369 | Trial terminated by Sponsor | 190 | 210 | 160 |
Baseline characteristics
| Characteristic | Vehicle Gel | Total | Ingenol Disoxate Gel 0.018% | Ingenol Disoxate Gel 0.037% |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 119 Participants | 408 Participants | 134 Participants | 155 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 155 Participants | 57 Participants | 55 Participants |
| Age, Continuous | 69 years | 70 years | 69 years | 71 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 12 Participants | 9 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 162 Participants | 550 Participants | 182 Participants | 206 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Fitzpatrick skin type Type I | 28 Participants | 88 Participants | 34 Participants | 26 Participants |
| Fitzpatrick skin type Type II | 94 Participants | 319 Participants | 109 Participants | 116 Participants |
| Fitzpatrick skin type Type III | 35 Participants | 131 Participants | 42 Participants | 54 Participants |
| Fitzpatrick skin type Type IV | 4 Participants | 21 Participants | 4 Participants | 13 Participants |
| Fitzpatrick skin type Type V | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 162 Participants | 561 Participants | 190 Participants | 209 Participants |
| Region of Enrollment Canada | 53 participants | 158 participants | 43 participants | 62 participants |
| Region of Enrollment France | 4 participants | 12 participants | 2 participants | 6 participants |
| Region of Enrollment Germany | 17 participants | 61 participants | 19 participants | 25 participants |
| Region of Enrollment Spain | 6 participants | 23 participants | 17 participants | 0 participants |
| Region of Enrollment United Kingdom | 12 participants | 37 participants | 12 participants | 13 participants |
| Region of Enrollment United States | 70 participants | 272 participants | 98 participants | 104 participants |
| Sex: Female, Male Female | 30 Participants | 97 Participants | 67 Participants | 0 Participants |
| Sex: Female, Male Male | 132 Participants | 466 Participants | 124 Participants | 210 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 191 | 0 / 211 | 2 / 161 |
| other Total, other adverse events | 16 / 191 | 6 / 211 | 10 / 161 |
| serious Total, serious adverse events | 0 / 191 | 1 / 211 | 0 / 161 |
Outcome results
Primary
Time to First Squamous Cell Carcinoma (SCC) in the Treatment Area
Time to first squamous cell carcinoma (SCC) in the treatment area. Relative difference between groups (ingenol disoxate vs vehicle) expressed as hazard ratio. The indicated measured values are the observed incidence rates of the SCC in the treatment area which form the basis of the statistical analysis of the time to event analysis
Time frame: From Visit 2 (6 months after Month 14 of main trial) to first SCC in the treatment area, up to 24 months
Population: Full Analysis Set: 1234 subjects who were randomised and applied IMP in one of 4 Main Trials
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ingenol Disoxate Gel 0.018% | Time to First Squamous Cell Carcinoma (SCC) in the Treatment Area | 2.77 SCC events per 100 patient years |
| Ingenol Disoxate Gel 0.037% | Time to First Squamous Cell Carcinoma (SCC) in the Treatment Area | 0.88 SCC events per 100 patient years |
| Vehicle Gel | Time to First Squamous Cell Carcinoma (SCC) in the Treatment Area | 1.26 SCC events per 100 patient years |
Comparison: Relative difference between groups (ingenol disoxate vs vehicle) expressed as hazard ratiop-value: 0.4395% CI: [0.61, 3.9]likelihood ratio test
Secondary
Time to First Squamous Cell Carcinoma (SCC) or Other Skin Neoplasia in the Treatment Area
Time to first squamous cell carcinoma (SCC) or other skin neoplasia in the treatment area. Relative difference between groups (ingenol disoxate vs vehicle) expressed as hazard ratio. The indicated measured values are the observed incidence rates of the SCC in the treatment area which form the basis of the statistical analysis of the time to event analysis
Time frame: From Visit 2 (6 months after Month 14 of main trial) to first SCC or other skin neoplasia in the treatment area, up to 24 months
Population: Full Analysis Set: 1234 subjects who were randomised and applied IMP in one of 4 Main Trials
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ingenol Disoxate Gel 0.018% | Time to First Squamous Cell Carcinoma (SCC) or Other Skin Neoplasia in the Treatment Area | 10.24 SCC events per 100 patient years |
| Ingenol Disoxate Gel 0.037% | Time to First Squamous Cell Carcinoma (SCC) or Other Skin Neoplasia in the Treatment Area | 2.84 SCC events per 100 patient years |
| Vehicle Gel | Time to First Squamous Cell Carcinoma (SCC) or Other Skin Neoplasia in the Treatment Area | 3.19 SCC events per 100 patient years |
Comparison: relative difference between treatment groups (ingenol disoxate gel vs vehicle) expressed as hazard ratiop-value: <0.0195% CI: [1.17, 3.62]likelihood ratio test