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Clinical Trial of Ingenol Mebutate Gel 0.015% & 0.05% in Actinic Keratosis

Primary Purpose

Actinic Keratosis

Status

Completed

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

ingenol mebutate gel 0.015%

ingenol mebutate gel 0.05%

About this trial

This is an interventional treatment trial for Actinic Keratosis focused on measuring Korean

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female aged ≥ 19 years
Histopathologically diagnosed AK patients with at least 1 macroscopic and discrete lesion within a contiguous 25 cm2 (e.g. 5 cm x 5 cm) of treatment area
The treatment area including the lesion must be accessible to apply the investigational product. However, the lesions on lips, mucosa, outer ear (concha) and those around eyes are excluded.
Subjects who signed the written informed consent prior to perform any study-related procedures or assessments, including photographs of their treatment area for documentation and efficacy assessment.

Exclusion Criteria:

Hypersensitivity to any components of the investigational product
History or evidence of skin conditions that could interfere with evaluation of the investigational product(e.g., eczema, unstable psoriasis, xeroderma pigmentosa, inflammatory or infectious disease around the selected treatment area)
Unhealed wound within 5 cm, or basal cell carcinoma or squamous cell carcinoma within 10 cm from the selected treatment area.
Subjects who received or expected to receive any of the following pharmacotherapy and non-pharmacotherapy or procedures during the treatment and follow-up period
Subjects who have following disorder or abnormal laboratory result
Pregnant, lactating, and childbearing potential women who are unwilling to practice effective contraception; for example, oral contraceptives, hormonal methods, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods (i.e., condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilization, and abstinence.
Subjects who previously underwent another clinical trial within 30 days or 5-times the half-life of previous investigational product prior to baseline (the longer period of time must be considered).
Other conditions by investigator's discretion to be inappropriate for this clinical study.

Sites / Locations

Korea University Ansan Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

ingenol mebutate gel 0.015%

ingenol mebutate gel 0.05%

Arm Description

Applied on face and scalp for three days.

Applied on trunk and extremities for two days.

Outcomes

Primary Outcome Measures

CC Rate of AK Lesions in the Selected Treatment Area

Complete Clearance (CC) means that clearance of all visible AK lesions in the selected treatment area and Investigator-rated actinic keratiosis(AK) lesion complete clearance (CC) rate at the selected treatment area on day 57 was analyzed.

Secondary Outcome Measures

Percentage Change of the Number of AK Lesions in the Selected Treatment Area

Percentage change from baseline in the number of actinic keratiosis(AK) lesions in the selected treatment area on Day 57 was analyzed.

Sustained CC Rate in CC Group

Sustained Complete Clearance means that Complete Clearance was maintained until Month 6 in complete clearance (CC) group and sustained complete clearance(CC) rate at month 6 for complete clearance(CC) group was analyzed.

Recurrence Rate in CC Group

Recurrence rate in complete clearance(CC) group was analyzed.

Percentage Change of the Number of AK Lesions in the Selected Treatment Area of CC Group

Percentage change from baseline in the number of actinic keratiosis(AK) lesions at Month 6 in the selected treatment area in complete clearance(CC) Group was analyzed.

Change From Baseline in Quality of Life (Skindex-29)

Skindex-29 is a self-administered QoL questionnaire comprised of 29 items scored on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=often, 4=all the time) covering 3 domains: emotional (10 items), symptomatic (7 items), and functional (12 items), with domain scores ranging from 0 to 40, 28, and 48, respectively. Lower scores for each of the domains represents a better Quality of life.

Treatment Satisfaction Questionnaire for Medication (TSQM)

Participants personally completed the tool to evaluate satisfaction with drug treatment. It consisted of 4 areas of Effectiveness, side effect, convenience, and global satisfaction, with a total of 14 sub-items. The full mark is 100, and it is divided in four stages as follows. Very good: 76 -100 score Good: 51-75 score Not bad: 26-50 score Bad: 0-25 score Scores for each area ranged from 0 to 100, with higher scores indicating that fewer side effects had occurred and greater treatment satisfaction.

Cosmetic Outcomes Assessment (COA)

The investigator rated the subject's Cosmetic Outcomes Assessment(COA) using 5 grades (Very good, Good, No change, Bad, Very bad), and results were as follows.

Time to Relapse in CC Group

Time to relapse in complete clearance(CC) Group was analyzed. Median survival time with 95% confidence interval was calculated by Kaplan-Meier method.

Full Information

NCT ID

NCT02716714

First Posted

January 28, 2016

Last Updated

April 16, 2018

Sponsor

Korea University

Collaborators

LEO Pharma, Chonnam National University Hospital, Severance Hospital, Ajou University School of Medicine, Asan Medical Center, Samsung Medical Center, Seoul National University Bundang Hospital, Dong-A University Hospital, Korea University Anam Hospital, Seoul National University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02716714

Brief Title

Clinical Trial of Ingenol Mebutate Gel 0.015% & 0.05% in Actinic Keratosis

Official Title

A Multi-center, OPen, InvEstigator Initiated Phase IV Clinical TRial to Evaluate the Efficacy and SaFety of Ingenol Mebutate Gel 0.015% on Face and Scalp & 0.05% on Trunk and Extremities in KorEan Patient With ACtinic KeraTosis (PERFECT)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Completed

Study Start Date

April 2015 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Korea University

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study evaluate the efficacy and safety of ingenol mebutate gel 0.015% on face and scalp & 0.05% on trunk and extremities in Korean patient with actinic keratosis.

Detailed Description

The mechanism of action of ingenol mebutate for actinic keratosis(AK) treatment involves a rapid induction of necrosis followed by neutrophil-mediated, antibody-dependent cellular cytotoxicity (ADCC) of residual lesion. As the ingenol mebutate infiltrates the cell membrane, it increases intracellular Ca2+ concentration which leads to mitochondrial swelling and disruption of mitochondrial membrane within hours. The release of intra-mitochondrial Ca2+ into the cytoplasm leads to depletion of adenosine triphosphate (ATP) and a rapid induction of cell death by necrosis. This process occurs within 1 hour of application, which explains why the treatment period requires only 2 or 3 days of treatment. As the next phase, the cellular necrosis is accompanied by a robust inflammatory response through the release of proinflammatory cytokines from skin cells and tumor cells undergoing necrosis. The release of these proinflammatory cytokines into the dysplastic cells mediates the process of neutrophil recruitment through paracrine signaling and activation of endothelial cells. Here, the neutrophil mediated ADCC occurs, where activated neutrophils attach to the fragment, crystallized (Fc) parts of antibodies of dysplastic cells and destroys the residual dysplastic epidermal cells. In this way, the ingenol mebutate eradicates any residual tumor cells and prevents recurrence of actinic keratosis.As described above, the rapid effect and dual mechanism of action of ingenol mebutate gel allows not only a short-course therapy (2 or 3 days of application) for the elimination of actinic keratosis but also, the benefit for eradication of any residual lesions preventing the recurrence and the progression of AK into squamous cell carcinoma (SCC).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Actinic Keratosis

Keywords

Korean

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

77 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ingenol mebutate gel 0.015%

Arm Type

Active Comparator

Arm Description

Applied on face and scalp for three days.

Arm Title

ingenol mebutate gel 0.05%

Arm Type

Active Comparator

Arm Description

Applied on trunk and extremities for two days.

Intervention Type

Drug

Intervention Name(s)

ingenol mebutate gel 0.015%

Other Intervention Name(s)

Picato® gel

Intervention Description

-Face or Scalp arm (Referred to Face/Scalp arm): Apply ingenol mebutate gel 0.015% once daily for 3 consecutive days

Intervention Type

Drug

Intervention Name(s)

ingenol mebutate gel 0.05%

Other Intervention Name(s)

Picato® gel

Intervention Description

-Trunk or Extremities arm (Referred to Trunk/Extremities arm): Apply ingenol mebutate gel 0.05% once daily for 2 consecutive days

Primary Outcome Measure Information:

Title

CC Rate of AK Lesions in the Selected Treatment Area

Description

Time Frame

at day 57

Secondary Outcome Measure Information:

Title

Percentage Change of the Number of AK Lesions in the Selected Treatment Area

Description

Percentage change from baseline in the number of actinic keratiosis(AK) lesions in the selected treatment area on Day 57 was analyzed.

Time Frame

Baseline and Day 57

Title

Sustained CC Rate in CC Group

Description

Time Frame

at 6 months

Title

Recurrence Rate in CC Group

Description

Recurrence rate in complete clearance(CC) group was analyzed.

Time Frame

at 6 months

Title

Percentage Change of the Number of AK Lesions in the Selected Treatment Area of CC Group

Description

Percentage change from baseline in the number of actinic keratiosis(AK) lesions at Month 6 in the selected treatment area in complete clearance(CC) Group was analyzed.

Time Frame

at 6 months from baseline

Title

Change From Baseline in Quality of Life (Skindex-29)

Description

Time Frame

at 29 and 57 days from baseline

Title

Treatment Satisfaction Questionnaire for Medication (TSQM)

Description

Time Frame

at 29 and 57 days from baseline

Title

Cosmetic Outcomes Assessment (COA)

Description

The investigator rated the subject's Cosmetic Outcomes Assessment(COA) using 5 grades (Very good, Good, No change, Bad, Very bad), and results were as follows.

Time Frame

at 29 and 57 days from baseline

Title

Time to Relapse in CC Group

Description

Time to relapse in complete clearance(CC) Group was analyzed. Median survival time with 95% confidence interval was calculated by Kaplan-Meier method.

Time Frame

at 6 months

Other Pre-specified Outcome Measures:

Title

Medication for Actinic Keratosis

Description

The count of participants in complete clearance(CC) group and Non-CC group who administered medication for actinic keratosis on the selected treatment area after Day 57 was collected.

Time Frame

from 57 days to 6 months

Title

Non-Drug Treatment/Surgery for Actinic Keratosis

Description

The count of participants in complete clearance(CC) group and Non-CC group who received non-drug treatment/surgery for actinic keratosis on the selected treatment area after Day 57 was collected.

Time Frame

from 57 days to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female aged ≥ 19 years Histopathologically diagnosed AK patients with at least 1 macroscopic and discrete lesion within a contiguous 25 cm2 (e.g. 5 cm x 5 cm) of treatment area The treatment area including the lesion must be accessible to apply the investigational product. However, the lesions on lips, mucosa, outer ear (concha) and those around eyes are excluded. Subjects who signed the written informed consent prior to perform any study-related procedures or assessments, including photographs of their treatment area for documentation and efficacy assessment. Exclusion Criteria: Hypersensitivity to any components of the investigational product History or evidence of skin conditions that could interfere with evaluation of the investigational product(e.g., eczema, unstable psoriasis, xeroderma pigmentosa, inflammatory or infectious disease around the selected treatment area) Unhealed wound within 5 cm, or basal cell carcinoma or squamous cell carcinoma within 10 cm from the selected treatment area. Subjects who received or expected to receive any of the following pharmacotherapy and non-pharmacotherapy or procedures during the treatment and follow-up period Subjects who have following disorder or abnormal laboratory result Pregnant, lactating, and childbearing potential women who are unwilling to practice effective contraception; for example, oral contraceptives, hormonal methods, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods (i.e., condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilization, and abstinence. Subjects who previously underwent another clinical trial within 30 days or 5-times the half-life of previous investigational product prior to baseline (the longer period of time must be considered). Other conditions by investigator's discretion to be inappropriate for this clinical study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ilhwan Kim, MD

Organizational Affiliation

Korea University Ansan Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Korea University Ansan Hospital

City

Ansan-si

State/Province

Gyeonggi-do

ZIP/Postal Code

15355

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual participant data for all primary and secondary outcome measures will be made within 6months of study completion.

Citations:

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Citation

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Clinical Trial of Ingenol Mebutate Gel 0.015% & 0.05% in Actinic Keratosis

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