PEP005 Gel - Biological Effects in Actinic Keratosis Assessed by Reflectance Confocal Microscopy

A Phase 1, Two-stage, Single-centre, Open Label, Within- and Between-subject Comparison Trial to Explore the Biological Effects of PEP005 (Ingenol Mebutate) Gel, 0.05%, Applied Once Daily for 2 Consecutive Days in Subjects With Actinic Keratosis on the Upper Extrem-ity. A Single-arm First Stage Followed by a Two-arm, Parallel Group, Randomized, Placebo (Vehicle) -Controlled Second Stage

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01449513

Enrollment

Registered

2011-10-10

Start date

2011-09-30

Completion date

2012-05-31

Last updated

2025-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Actinic Keratosis

Brief summary

This trial will be conducted to explore the biological effects in the skin following treatment with PEP005 Gel, 0.05% administered for two consecutive days, assessed by reflectance confocal microscopy.

Interventions

DRUGIngenol mebutate

0.05% Ingenol mebutate Gel once daily for 2 consecutive days

DRUGPlacebo Gel

Gel vehicle of PEP005

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Male or female subjects at least 18 years of age 2. Subjects with AK lesions and subclinical AK lesions within a contiguous 25 cm2 area on the upper extremity 3. Subjects must have a 25 cm2 area of normal skin on the inner upper arm 4. Female subjects must be of either:• Non-childbearing potential, post-menopausal, or have a confirmed clinical history of sterility or • Childbearing potential, with a confirmed negative urine pregnancy test prior to exposure. 5. Female subjects of childbearing potential must be willing to consent to using high effective methods of contraception 6. Ability to follow trial instructions and likely to complete all trial requirements 7. Obtained written informed consent prior to any trial-related procedures

Exclusion criteria

1. Location of the selected treatment areas:• Within 5 cm of an incompletely healed wound or infected area of the skin • Within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma(SCC) 2. History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the investigational product 3. Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety during the course of the trial, as determined by Investigator clinical judgment 4. Anticipated need for in-patient hospitalisation or in-patient surgery during the trial period. 5. Current participation in any other interventional clinical trial 6. Subjects who have received treatment with any non-marketed drug product within the last two months 7. Previous enrolment in this clinical trial 8. Prohibited Therapies and/or Medications 2 weeks prior to the Screening visit within 2 cm of selected treatment area:•Cosmetic or therapeutic procedures •Use of acid-containing therapeutic products • Use of topical salves or topical steroids 9. Prohibited Therapies and/or Medications: within 4 weeks prior to the Screening visit: • Treatment with immunomodulators, cytotoxic drugs or interferon/interferon inducers,systemic medications that suppress the immune system, or with UVB 10. Prohibited Therapies and/or Medications: within 8 weeks prior to the Screening visit: • Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy: within 2 cm of the selected treatment areas. 11. Use of systemic retinoids

Design outcomes

Primary

Measure	Time frame	Description
Change in Degree of Infiltration	Baseline to Day 2	Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by Reflectance Confocal Microscopy (RCM) in actinic keratosis (AK) skin.This RCM imaging technique is a relatively new non-invasive, real-time evaluation method to generate horizontal skin sections at a resolution comparable to routine histology. The degree of infiltration of the epidermis by inflammatory cells will be based on inflammation/small bright cells (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on inflammatory cells in the dermis (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.
Change in Degree of Necrosis	Baseline to Day 2	Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

Countries

Germany

Participant flow

Recruitment details

Start date: 27-Sep-2011 (FSFV - first subject first visit) Completion date: 22-May-2012 (LSLV - last subject last visit)

Participants by arm

Arm	Count
Ingenol Mebutate Gel (PEP005 Gel) Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	16
Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area	8
Total	24

Baseline characteristics

Characteristic	Vehicle	Ingenol Mebutate Gel (PEP005 Gel)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	8 Participants	14 Participants	22 Participants
Age, Categorical Between 18 and 65 years	0 Participants	2 Participants	2 Participants
Age, Continuous	69.9 years STANDARD_DEVIATION 3.5	70.8 years STANDARD_DEVIATION 7.5	70.5 years STANDARD_DEVIATION 6.3
Region of Enrollment Germany	8 participants	16 participants	24 participants
Sex: Female, Male Female	1 Participants	8 Participants	9 Participants
Sex: Female, Male Male	7 Participants	8 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	16 / 16	1 / 8
serious Total, serious adverse events	1 / 16	0 / 8

Outcome results

Primary

Change in Degree of Infiltration

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by Reflectance Confocal Microscopy (RCM) in actinic keratosis (AK) skin.This RCM imaging technique is a relatively new non-invasive, real-time evaluation method to generate horizontal skin sections at a resolution comparable to routine histology. The degree of infiltration of the epidermis by inflammatory cells will be based on inflammation/small bright cells (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on inflammatory cells in the dermis (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Time frame: Baseline to Day 2