A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp

• ingenol disoxate gel 0.018% (Drug), also known as LEO 43204: 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.
• ingenol disoxate gel 0.037% (Drug), also known as LEO 43204: 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.
• Vehicle gel (Other): Vehicle to ingenol disoxate gel with no active ingredient

Primary outcomes

• 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 outcomes

• 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

Sex: All

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.

Participant flow

Outcome results

• Time to First Squamous Cell Carcinoma (SCC) in the Treatment Area (Primary), Number, SCC events per 100 patient years: Ingenol Disoxate Gel 0.018% 2.77 (1.55 to 4.57); Ingenol Disoxate Gel 0.037% 0.88 (0.28 to 2.04); Vehicle Gel 1.26 (0.46 to 2.74) (p 0.43)
• Time to First Squamous Cell Carcinoma (SCC) or Other Skin Neoplasia in the Treatment Area (Secondary), Number, SCC events per 100 patient years: Ingenol Disoxate Gel 0.018% 10.24 (7.65 to 13.4); Ingenol Disoxate Gel 0.037% 2.84 (1.62 to 4.61); Vehicle Gel 3.19 (1.79 to 5.26) (p <0.01)

Adverse events

Time frame: From first visit in this trial until the end of the trial i.e a period of up to 9 months as the trial was prematurely discontinued

Serious adverse events by term

Other adverse events by term

Limitations and caveats: Early termination leading to small numbers of subjects analyzed

• Study Protocol (PDF, 2017-07-25)
• Statistical Analysis Plan (PDF, 2018-05-27)

NIH grants: 2017