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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
LEO Pharma
ClinicalTrials.gov Identifier:
NCT01449513
First received: October 6, 2011
Last updated: May 6, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Actinic Keratosis
Drug: Ingenol mebutate
Drug: Placebo Gel
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by LEO Pharma:

Primary Outcome Measures:
  • Change in Degree of Infiltration [ Time Frame: Baseline to Day 2 ] [ Designated as safety issue: No ]

    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 Infiltration [ Time Frame: Baseline to Day 2 ] [ Designated as safety issue: No ]

    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 Sub actinic keratosis (AK) skin.

    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 Infiltration [ Time Frame: Baseline to Day 2 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in normal skin.

    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 Infiltration [ Time Frame: Baseline to Day 3 ] [ Designated as safety issue: No ]
    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 RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

  • Change in Degree of Infiltration [ Time Frame: Baseline to Day 3 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin.

    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 Infiltration [ Time Frame: Baseline to Day 3 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in normal skin

    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 Infiltration [ Time Frame: Baseline to Day 8 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

    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 Infiltration [ Time Frame: Baseline to Day 8 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

    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 Infiltration [ Time Frame: Baseline to Day 8 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in normal skin

    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 Infiltration [ Time Frame: Baseline to Day 57 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

    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 Infiltration [ Time Frame: Baseline to Day 57 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

    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 Infiltration [ Time Frame: Baseline to Day 57 ] [ Designated as safety issue: No ]

    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 RCM (Reflectance Confocal Microscopy) in normal skin

    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 [ Time Frame: Baseline to Day 2 ] [ Designated as safety issue: No ]
    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

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 2 ] [ Designated as safety issue: No ]
    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 Sub AK (actinic keratosis) skin

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 2 ] [ Designated as safety issue: No ]
    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 normal skin

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 3 ] [ Designated as safety issue: No ]
    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

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 3 ] [ Designated as safety issue: No ]
    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 Sub AK (actinic keratosis) skin

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 3 ] [ Designated as safety issue: No ]
    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 normal skin

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 8 ] [ Designated as safety issue: No ]
    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

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 8 ] [ Designated as safety issue: No ]
    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 Sub AK (actinic keratosis) skin

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 8 ] [ Designated as safety issue: No ]
    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 normal skin

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 57 ] [ Designated as safety issue: No ]
    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

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 57 ] [ Designated as safety issue: No ]
    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 Sub AK (actinic keratosis) skin

  • Change in Degree of Necrosis [ Time Frame: Baseline to Day 57 ] [ Designated as safety issue: No ]
    Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM in normal skin


Enrollment: 24
Study Start Date: September 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PEP005 Gel 0.05%
active ingredient of PEP005: Ingenol mebutate
Drug: Ingenol mebutate
0.05% Ingenol mebutate Gel once daily for 2 consecutive days
Other Name: PEP005
Placebo Comparator: Placebo Gel
Vehicle of PEP005 Gel
Drug: Placebo Gel
Gel vehicle of PEP005

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01449513

Locations
Germany
Charité - Universitätsmedizin Berlin
Berlin, Germany, 10117
Sponsors and Collaborators
LEO Pharma
Investigators
Principal Investigator: Eggert Stockfleth, Prof Dr med Charite University, Berlin, Germany
  More Information

No publications provided

Responsible Party: LEO Pharma
ClinicalTrials.gov Identifier: NCT01449513     History of Changes
Other Study ID Numbers: LP0041-03
Study First Received: October 6, 2011
Results First Received: October 8, 2013
Last Updated: May 6, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Neoplasms
Precancerous Conditions
Skin Diseases

ClinicalTrials.gov processed this record on July 05, 2015