Trial Outcomes & Findings for Efficacy and Safety of Ingenol Mebutate Gel 0.06% When Applied Once Daily for 2, 3 or 4 Consecutive Days to a Treatment Area of Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis (NCT NCT01998984)
NCT ID: NCT01998984
Last Updated: 2025-03-10
Results Overview
Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in number of AKs. The table presents the mean across 1000 multiple imputations. Missing values for AK count were imputed sequentially from a negative binomial regression model with treatment group, AK counts at the previous visit, and analysis site as covariates and log baseline AK count as offset.
COMPLETED
PHASE2
266 participants
At Week 8
2025-03-10
Participant Flow
Participants were followed for 8 weeks following the first application of investigational medicinal product (IMP) at Day 1 (4-day treatment period including an 8-week follow-up period).
266 participants were enrolled of which 224 participants were randomized to treatment
Participant milestones
| Measure |
Ingenol 2 Days
Ingenol mebutate gel 0.06% and vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg). Vehicle gel was applied for 2 days and ingenol mebutate gel 0.06% was applied for 2 days for a total 4 consecutive days.
|
Ingenol 3 Days
Ingenol mebutate gel 0.06% and vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg). Vehicle gel was applied for 1 day and ingenol mebutate gel 0.06% was applied for 3 days for a total 4 consecutive days.
|
Ingenol 4 Days
Ingenol mebutate gel 0.06% applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg) for 4 consecutive days.
|
Vehicle
Vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg) for 4 consecutive days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
55
|
59
|
49
|
61
|
|
Overall Study
COMPLETED
|
55
|
58
|
48
|
58
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
3
|
Reasons for withdrawal
| Measure |
Ingenol 2 Days
Ingenol mebutate gel 0.06% and vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg). Vehicle gel was applied for 2 days and ingenol mebutate gel 0.06% was applied for 2 days for a total 4 consecutive days.
|
Ingenol 3 Days
Ingenol mebutate gel 0.06% and vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg). Vehicle gel was applied for 1 day and ingenol mebutate gel 0.06% was applied for 3 days for a total 4 consecutive days.
|
Ingenol 4 Days
Ingenol mebutate gel 0.06% applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg) for 4 consecutive days.
|
Vehicle
Vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg) for 4 consecutive days.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Overall Study
Other
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Efficacy and Safety of Ingenol Mebutate Gel 0.06% When Applied Once Daily for 2, 3 or 4 Consecutive Days to a Treatment Area of Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis
Baseline characteristics by cohort
| Measure |
Ingenol 2 Days
n=55 Participants
2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel
|
Ingenol 3 Days
n=59 Participants
3 days treatment with ingenol mebutate 0.06% gel and 1 day treatment with vehicle gel
|
Ingenol 4 Days
n=49 Participants
4 days treatment with ingenol mebutate 0.06% gel
|
Vehicle
n=61 Participants
4 days treatment with vehicle gel
|
Total
n=224 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
67.7 years
n=5 Participants
|
68.1 years
n=7 Participants
|
68.8 years
n=5 Participants
|
68.6 years
n=4 Participants
|
68.3 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
80 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
144 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
24 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
92 Participants
n=21 Participants
|
|
Region of Enrollment
Australia
|
31 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
132 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: At Week 8Population: The analysis was based on the Full Analysis Set, which was defined as all randomized participants.
Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in number of AKs. The table presents the mean across 1000 multiple imputations. Missing values for AK count were imputed sequentially from a negative binomial regression model with treatment group, AK counts at the previous visit, and analysis site as covariates and log baseline AK count as offset.
Outcome measures
| Measure |
Ingenol 2 Days
n=55 Participants
2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel
|
Ingenol 3 Days
n=59 Participants
1 day treatment with vehicle gel and 3 days treatment with ingenol mebutate 0.06% gel
|
Ingenol 4 Days
n=49 Participants
4 days treatment with ingenol mebutate 0.06% gel
|
Vehicle
n=61 Participants
4 days treatment with vehicle gel
|
|---|---|---|---|---|
|
Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs)
|
12.7 percentage of participants
|
5.1 percentage of participants
|
26.8 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: At Week 8Population: The analysis was based on the Full Analysis Set, which was defined as all randomized participants.
The number of clinically visible AK lesions identified in the treatment area was to be recorded at Visit 1(≤14 days prior to Day 1). The analysis was based on 1000 imputations of actinic keratosis lesion count at Week 8 using a negative binomial regression model with factors treatment and analysis site and with log of baseline actinic keratosis lesion count as offset. The table shows the adjusted percentage reduction from baseline. Values for the Ingenol 4 days arm were calculated separately based on observed cases. On the basis of the data monitoring committee's recommendation the 4-day active treatment group was closed, and this arm was excluded from statistical models and comparisons in the secondary efficacy analyses.
Outcome measures
| Measure |
Ingenol 2 Days
n=55 Participants
2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel
|
Ingenol 3 Days
n=59 Participants
1 day treatment with vehicle gel and 3 days treatment with ingenol mebutate 0.06% gel
|
Ingenol 4 Days
n=48 Participants
4 days treatment with ingenol mebutate 0.06% gel
|
Vehicle
n=61 Participants
4 days treatment with vehicle gel
|
|---|---|---|---|---|
|
Percentage of Reduction in Actinic Keratosis (AK) Lesion Count From Baseline (Day 1) (Multiple Imputation)
|
64.5 percentage of reduction
Interval 57.8 to 70.2
|
68.3 percentage of reduction
Interval 62.4 to 73.4
|
73.6 percentage of reduction
Interval 65.8 to 81.5
|
11.9 percentage of reduction
Interval -2.2 to 24.1
|
SECONDARY outcome
Timeframe: At Week 8Population: The analysis was based on the Full Analysis Set, which was defined as all randomized participants.
Partial clearance of AKs at Week 8, defined as at least 75% reduction from baseline in number of AKs, was analysed in the same way as the primary response criterion. The percent reduction at Week 8 from baseline was analyzed using a negative binomial regression for the AK count at Week 8 with treatment group and pooled sites as factors and baseline count as offset variable (using multiple imputations to account for missing values). The table presents the mean across 1000 multiple imputations. Missing values for AK count were imputed sequentially from a negative binomial regression model with treatment group, AK counts at the previous visit, and analysis site as covariates and log baseline AK count as offset.
Outcome measures
| Measure |
Ingenol 2 Days
n=55 Participants
2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel
|
Ingenol 3 Days
n=59 Participants
1 day treatment with vehicle gel and 3 days treatment with ingenol mebutate 0.06% gel
|
Ingenol 4 Days
n=49 Participants
4 days treatment with ingenol mebutate 0.06% gel
|
Vehicle
n=61 Participants
4 days treatment with vehicle gel
|
|---|---|---|---|---|
|
Percentage of Participants With Partial Clearance of AKs
|
47.3 percentage of participants
|
56.2 percentage of participants
|
60.4 percentage of participants
|
2.0 percentage of participants
|
Adverse Events
Ingenol 2 Days
Ingenol 3 Days
Ingenol 4 Days
Vehicle
Serious adverse events
| Measure |
Ingenol 2 Days
n=55 participants at risk
2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel
|
Ingenol 3 Days
n=59 participants at risk
1 day treatment with vehicle gel and 3 days treatment with ingenol mebutate 0.06% gel
|
Ingenol 4 Days
n=49 participants at risk
4 days treatment with ingenol mebutate 0.06% gel
|
Vehicle
n=61 participants at risk
4 days treatment with vehicle gel
|
|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
5.5%
3/55 • From Day 1 to Week 8 (Day 56)
|
6.8%
4/59 • From Day 1 to Week 8 (Day 56)
|
6.1%
3/49 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/61 • From Day 1 to Week 8 (Day 56)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Keratoacanthoma
|
0.00%
0/55 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/59 • From Day 1 to Week 8 (Day 56)
|
2.0%
1/49 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/61 • From Day 1 to Week 8 (Day 56)
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/55 • From Day 1 to Week 8 (Day 56)
|
1.7%
1/59 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/49 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/61 • From Day 1 to Week 8 (Day 56)
|
Other adverse events
| Measure |
Ingenol 2 Days
n=55 participants at risk
2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel
|
Ingenol 3 Days
n=59 participants at risk
1 day treatment with vehicle gel and 3 days treatment with ingenol mebutate 0.06% gel
|
Ingenol 4 Days
n=49 participants at risk
4 days treatment with ingenol mebutate 0.06% gel
|
Vehicle
n=61 participants at risk
4 days treatment with vehicle gel
|
|---|---|---|---|---|
|
General disorders
Application site pain
|
81.8%
45/55 • From Day 1 to Week 8 (Day 56)
|
84.7%
50/59 • From Day 1 to Week 8 (Day 56)
|
87.8%
43/49 • From Day 1 to Week 8 (Day 56)
|
4.9%
3/61 • From Day 1 to Week 8 (Day 56)
|
|
General disorders
Application site pruritus
|
34.5%
19/55 • From Day 1 to Week 8 (Day 56)
|
45.8%
27/59 • From Day 1 to Week 8 (Day 56)
|
28.6%
14/49 • From Day 1 to Week 8 (Day 56)
|
3.3%
2/61 • From Day 1 to Week 8 (Day 56)
|
|
General disorders
Application site discomfort
|
3.6%
2/55 • From Day 1 to Week 8 (Day 56)
|
5.1%
3/59 • From Day 1 to Week 8 (Day 56)
|
4.1%
2/49 • From Day 1 to Week 8 (Day 56)
|
1.6%
1/61 • From Day 1 to Week 8 (Day 56)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
1.8%
1/55 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/59 • From Day 1 to Week 8 (Day 56)
|
6.1%
3/49 • From Day 1 to Week 8 (Day 56)
|
1.6%
1/61 • From Day 1 to Week 8 (Day 56)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
1.8%
1/55 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/59 • From Day 1 to Week 8 (Day 56)
|
6.1%
3/49 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/61 • From Day 1 to Week 8 (Day 56)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/55 • From Day 1 to Week 8 (Day 56)
|
5.1%
3/59 • From Day 1 to Week 8 (Day 56)
|
2.0%
1/49 • From Day 1 to Week 8 (Day 56)
|
0.00%
0/61 • From Day 1 to Week 8 (Day 56)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Prior to submitting or presenting a manuscript relating to the clinical trial to a publisher, reviewer or other outside person, the investigator shall provide to LEO Pharma A/S a copy of all such manuscripts, and LEO Pharma A/S shall have rights to review and comment. Upon the request of LEO Pharma A/S the investigator shall remove any confidential information (other than results generated by the investigator) prior to submitting or presenting the manuscripts.
- Publication restrictions are in place
Restriction type: OTHER