Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Keratosis, Actinic

Keratosis

Skin Diseases

Precancerous Conditions

Chiari Malformation Type 2

Open-label, dose-escalation, 2-day treatment

LEO 43204 dose 0.1% once daily for two consecutive days

LEO 43204 dose 0.075% once daily for two days

LEO 43204

Placebo

Gary Goldenberg, MD

Part 1: To identify Maximum Tolerated Dose (MTD) levels of LEO 43204 after once daily treatment for two consecutive days

Part 2: To evaluate the efficacy of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle

Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis

The number participants experiencing a DLT was used to identify the maximum tolerated dose(MTD) levels of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level at which less than 4 out of 12 participants experienced a DLT.

A DLT was defined as one or more of the following three LSRs:

* Crusting Grade 4
* Erosion/Ulceration Grade 4
* Vesiculation/Pustulation Grade 4

or two or more of the following five LSRs:

* Crusting Grade 3
* Swelling Grade 4
* Erosion/Ulceration Grade 3
* Vesiculation/Pustulation Grade 3

or other clinically relevant signs or symptoms observed, which the Investigator judged to be counted as a DLT.

The LSRs consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category was given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity.

Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) identified in the treatment area.

Complete clearance was defined as a 100% reduction from baseline in AK count.

Partial clearance was defined as at least 75% reduction from baseline in AK count.

LEO Pharma

Once daily treatment for two consecutive days with LEO 43204 gel 0.018%

Part 1: LEO 43204 Gel 0.018%

Once daily treatment for two consecutive days with LEO 43204 gel 0.025%

Part 1: LEO 43204 Gel 0.025%

Once daily treatment for two consecutive days with LEO 43204 gel 0.037%

Part 1: LEO 43204 Gel 0.037%

Once daily treatment for two consecutive days with LEO 43204 gel 0.05%

Part 1: LEO 43204 Gel 0.05%

Once daily treatment for two consecutive days with LEO 43204 gel 0.075%

Part 1: LEO 43204 Gel 0.075%

Once daily treatment for two consecutive days with LEO 43204 gel 0.1%

Part 1: LEO 43204 Gel 0.1%

Once daily treatment for two consecutive days LEO 43204 vehicle gel

Part 2: LEO 43204 Vehicle Gel

Once daily treatment for two consecutive days LEO 43204 gel 0.075%

Part 2: LEO 43204 Gel 0.075%

Once daily treatment for two consecutive days LEO 43204 gel 0.1%

Part 2: LEO 43204 Gel 0.1%

Total

Age, Categorical

Sex: Female, Male

Canada

United States

Region of Enrollment

Clinical Trial Disclosure Specialist

Part 1: Participants Experiencing Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs)

Negative binominal regression with log baseline count as offset variable and treatment group and analysis site as factors.

Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Count

Log binomial regression with factors treatment group and baseline AK count as a covariate.

Part 2: Participants With Complete Clearance of AKs (Last Observation Carried Forward [LOCF])

Part 2: Participants With Partial Clearance of AKs (LOCF)

Once daily treatment for two consecutive days with LEO 43204 gel 0.018% on sun exposed area of 250 cm2 on the arm between wrist and shoulder.

Once daily treatment for two consecutive days with LEO 43204 gel 0.025% on sun exposed area of 250 cm2 on the arm between wrist and shoulder.

Once daily treatment for two consecutive days with LEO 43204 gel 0.037% on sun exposed area of 250 cm2 on the arm between wrist and shoulder.

Once daily treatment for two consecutive days with LEO 43204 gel 0.05% on sun exposed area of 250 cm2 on the arm between wrist and shoulder.

Once daily treatment for two consecutive days with LEO 43204 gel 0.075% on sun exposed area of 250 cm2 on the arm between wrist and shoulder.

Once daily treatment for two consecutive days with LEO 43204 gel 0.1% on sun exposed area of 250 cm2 on the arm between wrist and shoulder.

Once daily treatment for two consecutive days with LEO 43204 vehicle gel on sun exposed area of 250 cm2 on the extremities or trunk (except chest).

Once daily treatment for two consecutive days with LEO 43204 gel 0.075% on sun exposed area of 250 cm2 on the extremities or trunk (except chest).

Once daily treatment for two consecutive days with LEO 43204 gel 0.1% on sun exposed area of 250 cm2 on the extremities or trunk (except chest).

Part 1 Open-label, Dose-escalation Phase

Part 2 Double-blind Phase

Symptoms and General Pathology

Alopecia

Alopecia Areata

Open-label, dose escalation, 2 days treatment

Jonathan Weiss, MD

To identify the Maximum Tolerated Dose levels of LEO 43204 after once daily treatment for two consecutive days and to evaluate efficacy of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle

Safety and Efficacy of Doses of LEO 43204 Once Daily for Two Consecutive Days on Full Balding Scalp in Subjects With Actinic Keratosis

Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Full Balding Scalp in Subjects With Actinic Keratosis

The number participants experiencing a DLT was used to identify the maximum tolerated dose (MTD) of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level with less than 4 out of 12 participants experiencing a DLT.

A DLT was defined as:

* Erosion/ulceration Grade 4 on the Local Skin Response (LSR) scale
* Other clinically relevant signs or symptoms observed, which the International Co-ordinating Investigator judges to be counted as a DLT.

The Local Skin Responses consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category are given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity.

Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) in the selected treatment area.

Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in AK count.

Partial clearance of AKs at Week 8 was defined as at least 75% reduction from baseline in AK count.

Part 1 - Dose escalation

Once daily application with LEO 43204 gel 0.018% for two consecutive days on balding scalp.

Part 1 - 0.018% Cohort

Part 1 - Dose escalation

Once daily application with LEO 43204 gel 0.025%for two consecutive days on balding scalp.

Part 1 - 0.025% Cohort

Part 1 - Dose escalation

Once daily application with LEO 43204 gel 0.036% for two consecutive days on balding scalp.

Part 1 - 0.037% Cohort

Part 1 - Dose escalation

Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp.

Part 1 - 0.05% Cohort

Part 1 - Dose escalation

Once daily application with LEO 43204 gel 0.075% for two consecutive days on balding scalp.

Part 1 - 0.075% Cohort

Part 2 - Dose finding

Once daily application with LEO 43204 gel vehicle for two consecutive days on balding scalp.

Part 2 - Vehicle

Part 2 - Dose finding

Once daily application with LEO 43204 gel 0.037% for two consecutive days on balding scalp.

Part 2 - 0.037%

Part 2 - Dose finding

Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp.

Part 2 - 0.05%

Part 1 - Dose escalation

Once daily application with LEO 43204 gel 0.025% for two consecutive days on balding scalp.

Part 1 - Dose escalation

Once daily application with LEO 43204 gel 0.037% for two consecutive days on balding scalp.

Germany

Part 1: Number of Participants Experiencing a Dose-limiting Toxicity (DLT)

Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Lesion Count

Log binomial regression with treatment group as factor and baseline AK count included as covariate.

Part 2: Participants With Complete Clearance of AKs

Part 2: Participants With Partial Clearance of AKs

Part 1 - Dose escalation

Once daily application with LEO 43204 gel (ingenol disoxate) 0.018% for two consecutive days on balding scalp.

Overall Study

LEO 43204 will be applied topically to the skin under open conditions 10 times

LEO 43204 vehicle will be applied topically to the skin under open conditions 10 times

LEO 43204 Vehicle

This is a randomized, single-center, controlled, within-subject comparison study assessing the sensitization potential of the investigational product, LEO 43204 gel under open conditions in healthy volunteers.

LEO 43204 Gel and Vehicle Gel will be applied to adjacent sites on the infrascapular area of the back. Evaluation of dermal reactions at the application sites will be assessed clinically using a visual scale that rates the degree of erythema, edema and other signs of cutaneous irritation.

Following induction, subjects will have a 10 to 14-day Rest Phase, after which they will enter the Challenge Phase, which consists of one 48-hour application to a naive site on the opposite side of the back. Observations at the naive site during Challenge and the patterns of reactivity during the Induction Phase will provide a basis for an interpretation of contact sensitization.

A total of 10 applications will be made over a period of approximately 6-8 weeks.

A Clinical Study to Evaluate the Sensitizing Potential of LEO 43204 Gel

A Randomized, Controlled Study to Evaluate the Sensitizing Potential of LEO 43204 Gel and Gel Vehicle in Healthy Volunteers Using a Repeat Insult Patch Test Design

Facies

Daniel M Siegel, MD

The objective of the trial is to investigate the Safety of LEO 43204 0.018%, 0.037% and 0.1% for actinic keratosis applied once daily for three consecutive days on face/chest, scalp and trunk/extremities, respectively.

Safety of LEO 43204 for Actinic Keratosis Applied on Face/Chest, Scalp and Trunk/Extremities, Respectively

Safety of LEO 43204 0.018%, 0.037% and 0.1% for Actinic Keratosis Applied Once Daily for Three Consecutive Days on Face/Chest, Scalp and Trunk/Extremities, Respectively

For face/chest, a DLT was defined as one or more of the following three LSRs:

* Crusting Grade 4
* Erosion/Ulceration Grade 4
* Vesiculation/Pustulation Grade 4

Or two or more of the following five LSRs:

* Erythema Grade 4
* Crusting Grade 3
* Swelling Grade 4
* Erosion/Ulceration Grade 3
* Vesiculation/Pustulation Grade 3

For scalp a DLT was defined as erosion/ulceration Grade 4

For trunk/extremities a DLT was defined as one or more of the following three LSRs:

* Crusting Grade 4
* Erosion/Ulceration Grade 4
* Vesiculation/Pustulation Grade 4

Or two or more of the following four LSRs:

* Crusting Grade 3
* Swelling Grade 4
* Erosion/Ulceration Grade 3
* Vesiculation/Pustulation Grade 3

The number of clinically visible actinic keratosis lesions (AKs) identified in the treatment area was recorded at baseline (Day 1), Week 4, and Week 8. This analysis excluded lesions identified at baseline as hypertrophic/hyperkeratotic.

Hypertrophic/Hyperkeratotic lesions were identified at baseline (Day 1), Week 4 and Week 8.

Complete clearance was defined as no clinically visible AKs. This analysis excluded lesions identified at baseline as hypertrophic/hyperkeratotic.

Treatment with LEO 43204 0.018% gel once daily for 3 consecutive days on the full face or a contiguous area on the chest of approximately 250 cm2.

LEO 43204 0.018% Face/Chest

Treatment with LEO 43204 0.037% gel once daily for 3 consecutive days on the full balding scalp of an area greater than 25 cm2 and up to approximately 250 cm2.

LEO 43204 0.037% Scalp

Treatment with LEO 43204 0.1% gel once daily for 3 consecutive days on a contiguous area of approximately 250 cm2 on trunk or extremities (excluding chest).

LEO 43204 0.1% Trunk/Extremities

Age, Continuous

The baseline analysis population was based on the full analysis set, defined as all participants who assigned to treatment and who met the inclusion criteria.

Number of Participants Experiencing DLTs (Dose Limiting Toxicities) Based on LSRs (Local Skin Reactions)

Week 4

Week 8

Percent Reduction in AK Count Excluding Lesions Identified at Baseline as Hypertrophic/Hyperkeratotic

For this efficacy analysis only participants with lesions identified as hypertrophic/hyperkeratotic at baseline were included in the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis	NCT02120456	Actinic Keratos...	LEO 43204 Placebo	18 Years -	LEO Pharma
Safety and Efficacy of Doses of LEO 43204 Once Daily for Two Consecutive Days on Full Balding Scalp in Subjects With Actinic Keratosis	NCT02100813	Actinic Keratos...	LEO 43204 Placebo	18 Years -	LEO Pharma
Safety and Efficacy of Doses of LEO 43204 Once Daily for Two Consecutive Days on Full Balding Scalp in Subjects With Actinic Keratosis	NCT02100813	Actinic Keratos...	LEO 43204 Placebo	18 Years -	LEO Pharma
A Clinical Study to Evaluate the Sensitizing Potential of LEO 43204 Gel	NCT02650505	Actinic Keratos...	LEO 43204 LEO 43204 Vehic...	18 Years - 65 Years	LEO Pharma
Safety of LEO 43204 for Actinic Keratosis Applied on Face/Chest, Scalp and Trunk/Extremities, Respectively	NCT02305888	Actinic Keratos...	LEO 43204	18 Years -	LEO Pharma

Spots Global Cancer Trial Database for leo 43204

Every month we try and update this database with for leo 43204 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for leo 43204

Every month we try and update this database with for leo 43204 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for leo 43204 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.