Neoplasms

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Carcinoma

Carcinoma, Squamous Cell

Facies

Keratosis, Actinic

Keratosis

Skin Diseases

Precancerous Conditions

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Imiquimod

Immunomodulating Agents

Immunologic Factors

Adjuvants, Immunologic

Interferons

Arm A: Ingenol mebutate gel 0.015% applied daily for 3 consecutive days to the selected treatment area followed by 8 weeks' rest. Retreatment for another 3 consecutive days if the treatment field is not completely cleared of AKs at Week 8

Arm B: Imiquimod 5% cream applied 3 days per week for 4 weeks to the selected treatment area followed by 4 weeks' rest. Retreatment for another 4 weeks if the treatment field is not completely cleared of AKs at Week 8

Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.

Ingenol Mebutate Gel, 0.015%

Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs

Imiquimod Cream, 5%

Rolf-Markus Szeimies, Prof.Dr.med.

The purpose of the study is to compare the risk of developing squamous skin cancer (SCC) or other types of cancer after treatment of AKs with ingenol mebutate gel or imiquimod cream. Subjects will be randomised to treatment with ingenol mebutate or imiquimod and will receive a second treatment cycle with the same treatment if the first treatment does not clear all AKs. Subjects will be followed over a period of three year (36 months) after first treatment

Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%

A Phase 4 Trial Comparing the Cumulative Incidence of SCC After Treatment With Ingenol Mebutate and Imiquimod for Multiple Actinic Keratoses on Face and Scalp. A Multi-centre, Randomised, Two-arm, Open Label, Active-controlled, Parallel Group, 36-month Trial

Cumulative incidence of SCC after treatment with ingenol mebutate gel and imiquimod cream.\> The primary response criterion is diagnosis of SCC (defined as invasive SCC i.e. excludes SCC in situ) in the treatment field across the 3-year trial period.\> Kaplan-Meier estimate based on time to SCC or censoring.

Cumulative incidence of SCC and other neoplasia after treatment with ingenol mebutate gel and imiquimod cream.\> The secondary response criterion is diagnosis of SCC and other neoplasia in the treatment field across the 3-year trial period.\> Kaplan-Meier estimate based on time to SCC and other neoplasia, or censoring.

To compare the complete clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)

To compare the partial (at least 75%) clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16)

To compare the complete clearance of AK lesions at 12 months, defined as no AK lesions in the selected treatment area at any time from the last treatment cycle at Week 8 or 16 through to Month 12.

LEO Pharma

Adverse events (AEs) were reported differently before and after Week 20. Week 20 is the first week of the follow-up period. Before Week 20, all AEs and serious AEs were recorded; after Week 20, all AEs inside the treatment area but only BCC/SCC and related SAEs outside the treatment area, were recorded.

As per above rules, there were deaths occuring after Week 20 without an associated AE recorded. However, all deaths in the trial are included under "All-Cause Mortality"

Ingenol mebutate gel 0.015% applied daily for 3 consecutive days to the selected treatment area followed by 8 weeks' rest. Retreatment for another 3 consecutive days if the treatment field is not completely cleared of AKs at Week 8.

Ingenol Mebutate Gel, 0.015%: Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.

Ingenol Mebutate Until Week 20

Imiquimod 5% cream applied 3 days per week for 4 weeks to the selected treatment area followed by 4 weeks' rest. Retreatment for another 4 weeks if the treatment field is not completely cleared of AKs at Week 8 Imiquimod Cream, 5%: Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs

Imiquimod Until Week 20

Ingenol mebutate Week 20 is the first week of the follow-up period.

Ingenol Mebutate After Week 20

Imiquimod Week 20 is the first week of the follow-up period.

Imiquimod After Week 20

Arm A: Ingenol mebutate gel 0.015% applied daily for 3 consecutive days to the selected treatment area followed by 8 weeks' rest. Retreatment for another 3 consecutive days if the treatment field is not completely cleared of AKs at Week 8\>

\> Ingenol Mebutate Gel, 0.015%: Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.

Ingenol Mebutate

Arm B: Imiquimod 5% cream applied 3 days per week for 4 weeks to the selected\> treatment area followed by 4 weeks' rest. Retreatment for another 4 weeks if the treatment field is not completely cleared of AKs at Week 8\>

\> Imiquimod Cream, 5%: Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United Kingdom

France

Germany

Region of Enrollment

In total, 485 subjects were randomised (full analysis set), but 1 subject (randomised in United Kingdom) was not treated. To support the primary safety endpoints, all baseline and safety results are based on the 484 subjects. Efficacy analysis are based on all 485 randomized subjects due to the intention-to-treat principle.

Disclosure

Safety analysis set: all treated subjects

Incidence of SCC

Incidence of SCC and Other Neoplasia

Arm A: Ingenol mebutate gel 0.015% applied daily for 3 consecutive days to the selected treatment area followed by 8 weeks' rest. Retreatment for another 3 consecutive days if the treatment field is not completely cleared of AKs at Week 8 \>

\> Ingenol Mebutate Gel, 0.015%: Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.

Arm B: Imiquimod 5% cream applied 3 days per week for 4 weeks to the selected

\> treatment area followed by 4 weeks' rest. Retreatment for another 4 weeks if the treatment field is not completely cleared of AKs at Week 8

\>

\> Imiquimod Cream, 5%: Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs

Full analysis set: all randomised subjects

Number of Participants With Complete Clearance of AK Lesions After Last Treatment

Number of Participants With Partial Clearance of AK Lesions

Full analysis set: all randomised subjects.

Number of Participants With Complete Clearance of AK Lesions at 12 Months

Overall Study

Fluorouracil

5-FU Cream

Efudex®

Vehicle

To compare the relative efficacy and safety and of 5-FU Cream to the marketed formulation Efudex® (5-FU) Cream, and to demonstrate the superior efficacy of the two active formulations over that of the Vehicle Control Cream, in the treatment of actinic keratosis.

To compare the safety and efficacy profiles of 5-FU Cream with Efudex® (5-FU) Cream, and to demonstrate the superior efficacy of the two active formulations over that of the Vehicle Control Cream, in the treatment of actinic keratosis.

Bioequivalence Study to Compare Sol-Gel Technologies' 5-FU Cream With Efudex® (5-FU) Cream

A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group Bioequivalence Study to Compare Sol-Gel Technologies' 5-FU Cream, With Efudex® (5-FU) Cream, and Both Active Treatments to a Vehicle Control, in the Treatment of Actinic Keratosis

Proportion of subjects, in the Per-Protocol (PP) population, with treatment success, defined as complete clearing (100% clearance of all AK lesions within the designated treatment area) at the End of Study visit

Sol-Gel Technologies, Ltd.

Low dose DFD07 once daily

High dose DFD07 once daily

High dose DFD07 twice daily

Placebo twice daily

Srinivas R. Sidgiddi, M.D.

Once or twice daily 12 week treatment in patients with Actinic Keratosis randomized to treatment in one of four arms.

A Study to Evaluate Two Concentrations of DFD-07 Cream, in Subjects With Actinic Keratosis (AK) of the Face and/or Scalp Over a 12-week Treatment Period

A Multi-Center, Randomized, Double-Blind, Parallel-Group, Vehicle-Controlled Study to Evaluate the Dose-Response Relationship of the Efficacy and Safety of Two Concentrations of DFD-07 Cream, in Subjects With Actinic Keratosis (AK) of the Face and/or Scalp Over a 12-week Treatment Period.

The proportion of subjects with complete clearance (absence of clinically visible or palpable AK lesions in the treatment area) of AK lesions at the End of Study Visit at 16 weeks (12 weeks treatment and 4 weeks treatment-free follow-up)

Proportion of subjects with partial clearance of AK lesions at week 16 (12 weeks treatment and 4 weeks treatment free follow up period)

Dr. Reddy's Laboratories Limited

DFD07 Cream (Celecoxib 1.25%) Once daily for 12 weeks followed by 4 weeks treatment-free period. In this group active treatment was applied once daily in the evening and Vehicle treatment was applied once daily in the morning for 12 weeks to maintain study blind.

DFD07 Cream (Celecoxib 1.25%) Once Daily

DFD07 Cream (Celecoxib 2.5%) Once daily for 12 weeks followed by 4 weeks treatment-free period. In this group active treatment was applied once daily in the evening and Vehicle treatment was applied once daily in the morning for 12 weeks to maintain study blind.

DFD07 Cream (Celecoxib 2.5%) Once Daily

DFD07 Cream (Celecoxib 2.5%) Twice daily for 12 weeks followed by 4 weeks treatment-free period

DFD07 Cream (Celecoxib 2.5%) Twice Daily

Vehicle Cream (Celecoxib 0%) Twice daily for 12 weeks followed by 4 weeks treatment-free period

Vehicle Cream (Celecoxib 0%) Twice Daily

DFD07 Cream (celecoxib 1.25%) once daily:

The active investigational product was applied once daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment. In this group, the randomized active DFD-07 (celecoxib 1.25%) Cream product was applied once daily in the evening, while the Vehicle for DFD-07 Cream was applied once daily in the morning to keep the blinding between groups.

DFD07 Cream 1.25% Once Daily

DFD07 Cream (celecoxib 2.5%) once daily:

The active investigational product was applied once daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment. In this group, the randomized active DFD-07 (celecoxib 2.5%) Cream product was applied once daily in the evening, while the Vehicle for DFD-07 Cream was applied once daily in the morning to keep the blinding between groups.

DFD07 Cream 2.5% Once Daily

DFD07 Cream (celecoxib 2.5%) twice daily:

The active investigational product was applied twice daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment.

DFD07 Cream 2.5% Twice Daily

Vehicle Cream (celecoxib 0%) twice daily:

The Vehicle Cream was applied twice daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment.

Vehicle Cream Twice Daily

United States

Dr. Srinivas Sidgiddi

Intent To Treat (ITT) population defined as all subjects who were randomized and dispensed study medication.

Proportion of Subjects With Complete Clearance of AK Lesions at the End of Study Visit at 16 Weeks

Proportion of Subjects With Partial Clearance at Week 16

Low dose DFD07 (1.25%) once daily:

The active investigational product was applied once daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment. The dose for the study product was a maximum of 0.5 g per application to the entire 5 cm x 5 cm area on the face and/or scalp for a maximum dose of 0.5 g per day. In this group, the randomized active DFD-07 (celecoxib) Cream product was applied once daily in the evening, while the Vehicle for DFD-07 Cream was applied once daily in the morning to keep the blinding between groups.

DFD07 - 1.25% Once Daily

High dose DFD07 (2.5%) once daily:

The active investigational product was applied once daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment. The dose for the study product was a maximum of 0.5 g per application to the entire 5 cm x 5 cm area on the face and/or scalp for a maximum dose of 0.5 g per day. In this group, the randomized active DFD-07 (celecoxib) Cream product was applied once daily in the evening, while the Vehicle for DFD-07 Cream was applied once daily in the morning to keep the blinding between groups.

DFD07 - 2.5% Once Daily

High dose DFD07 (2.5%) twice daily: The active investigational product was applied twice daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment. The dose for the study product was a maximum of 0.5 g per application to the entire 5 cm x 5 cm area on the face and/or scalp for a maximum dose of 1.0 g per day.

DFD07 - 2.5% Twice Daily

Vehicle twice daily:

The Vehicle product was applied twice daily for 12 weeks to cover the entire lesional area (5 cm x 5 cm) on the face and/or scalp identified by the Investigator for treatment. The dose for the Vehicle product was a maximum of 0.5 g per application to the entire 5 cm x 5 cm area on the face and/or scalp for a maximum dose of 1.0 g per day.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%	NCT01926496	Actinic Keratos...	Ingenol Mebutat... Imiquimod Cream...	18 Years -	LEO Pharma
Bioequivalence Study to Compare Sol-Gel Technologies' 5-FU Cream With Efudex® (5-FU) Cream	NCT03727074	Actinic Keratos...	5-FU Cream Efudex® Vehicle	18 Years -	Sol-Gel Technologies, Ltd.
Bioequivalence Study to Compare Sol-Gel Technologies' 5-FU Cream With Efudex® (5-FU) Cream	NCT03727074	Actinic Keratos...	5-FU Cream Efudex® Vehicle	18 Years -	Sol-Gel Technologies, Ltd.
A Study to Evaluate Two Concentrations of DFD-07 Cream, in Subjects With Actinic Keratosis (AK) of the Face and/or Scalp Over a 12-week Treatment Period	NCT03116698	Actinic Keratos...	Low dose DFD07 ... High dose DFD07... High dose DFD07... Placebo twice d...	18 Years - 65 Years	Dr. Reddy's Laboratories Limited
Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%	NCT01926496	Actinic Keratos...	Ingenol Mebutat... Imiquimod Cream...	18 Years -	LEO Pharma
A Study to Evaluate Two Concentrations of DFD-07 Cream, in Subjects With Actinic Keratosis (AK) of the Face and/or Scalp Over a 12-week Treatment Period	NCT03116698	Actinic Keratos...	Low dose DFD07 ... High dose DFD07... High dose DFD07... Placebo twice d...	18 Years - 65 Years	Dr. Reddy's Laboratories Limited

Spots Global Cancer Trial Database for actinic keratosis (ak)