Actinic Keratosis
Conditions
Brief summary
The purpose of this trial is to compare the rate of complete clearance of actinic keratosis (AK) using sequential cryotherapy and field treatment with PEP005 Gel compared to cryotherapy alone.
Interventions
PROCEDURECryotherapy
Cryotherapy of all visible AKs (4-8 lesions, baseline lesions) in the selected treatment area
DRUGVehicle
Field treatment with vehicle gel once daily for 3 consecutive days.
DRUGIngenol metabute
Field treatment with vehicle gel once daily for 3 consecutive days.
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be competent to understand the nature of the trial and provide informed consent. * Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous 25 cm2 treatment area on the face or scalp. * Subject at least 18 years of age. * Female subjects must be of either: * Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or, * Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to study treatment, to rule out pregnancy. * Female subjects of childbearing potential must be willing to use effective contraception.
Exclusion criteria
* Location of the selected treatment area: * on any location other than the face or scalp * within 5 cm of an incompletely healed wound * within 10 cm of a suspected basal cell carcinoma (BCC) or SCC * Prior treatment with PEP005 Gel on face or scalp. * Selected treatment area lesions that have: * atypical clinical appearance and/or * recalcitrant disease * History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the trial medication * 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 and efficacy. * Any abnormal vital signs measurements that are medically significant or would impact the safety of the subject or the interpretation of the trial results. * Anticipated need for hospitalization or out-patient surgery during the first 15 days after the first trial medication application. * Known sensitivity or allergy to any of the ingredients in PEP005 Gel * Recent excessive exposure to ultraviolet light * Current enrolment or participation in a clinical trial within 30 days of entry into this study * Subjects previously randomised in the trial * Female subjects who are breastfeeding Prohibited Therapies and/or Medications within 2 weeks prior to Visit 1 * Cosmetic or therapeutic procedures within 2 cm of the selected treatment area * Use of acid-containing therapeutic products within 2 cm of the selected treatment area * Use of topical medicated creams, ointments, lotions, gels, foams or sprays Prohibited Therapies and/or Medications: within 4 weeks prior to visit 1: * Treatment with immunomodulators, cytotoxic drugs or inter-feron /interferon inducers * Treatment with systemic medications that suppress the immune system * Treatment/therapy with ultraviolet light A (UVA) or ultraviolet light B (UVB). Prohibited Therapies and/or Medications within 8 weeks prior to visit 1: * Treatment with 5-FU, imiquimod, diclofenac sodium, or photodynamic therapy: within 2 cm of the selected treatment area. Prohibited Therapies and/or Medications within 6 months prior to visit 1 * Use of systemic retinoids or biologic / mono-clonal antibody therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Clearance of AKs at Week 11 | 11 weeks | To determine the 11-week rate of complete clearance of AKs (defined as no clinically visible AKs) in the selected treatment area using sequential cryotherapy and field treatment with PEP005 Gel compared to cryotherapy alone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Number of AKs at Week 11 | Baseline to week 11 | Percentage change from baseline in number of AKs at Week 11 |
| Partial Clearance of AKs at Week 11 | Week 11 | Partial clearance of AKs at Week 11, defined as 75% or greater reduction from baseline in the number of clinically visible AKs in the selected treatment area at Week 11 |
Countries
United States
Participant flow
Pre-assignment details
A total of 367 subjects were enrolled of whom 38 were screen failures. The remaining 329 subjects were randomised at Visit 1.
Participants by arm
| Arm | Count |
|---|---|
| PEP005 Gel, 0.015% Cryotherapy followed by PEP005 Gel, 0.015%
Cryotherapy of all visible AKs (4-8 lesions, baseline AKs) in the selected treatment area, 2-4 weeks healing time followed by field treatment with PEP005 gel, 0.015% once daily for 3 consecutive days | 167 |
| Vehicle Gel Cryotherapy followed by vehicle gel
Cryotherapy of all visible AKs (4-8 lesions, baseline AKs) in the selected treatment area, 2-4 weeks healing time followed by field treatment with vehicle gel once daily for 3 consecutive days. | 162 |
| Total | 329 |
Baseline characteristics
| Characteristic | PEP005 Gel, 0.015% | Vehicle Gel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 95 Participants | 101 Participants | 196 Participants |
| Age, Categorical Between 18 and 65 years | 72 Participants | 61 Participants | 133 Participants |
| Age, Continuous | 66.7 years STANDARD_DEVIATION 9.4 | 67.4 years STANDARD_DEVIATION 9.3 | 67 years STANDARD_DEVIATION 9.3 |
| Region of Enrollment United States | 167 participants | 162 participants | 329 participants |
| Sex: Female, Male Female | 29 Participants | 29 Participants | 58 Participants |
| Sex: Female, Male Male | 138 Participants | 133 Participants | 271 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 167 | 0 / 162 |
| serious Total, serious adverse events | 7 / 167 | 4 / 162 |
Outcome results
Primary
Complete Clearance of AKs at Week 11
To determine the 11-week rate of complete clearance of AKs (defined as no clinically visible AKs) in the selected treatment area using sequential cryotherapy and field treatment with PEP005 Gel compared to cryotherapy alone.
Time frame: 11 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEP005 Gel, 0.015% | Complete Clearance of AKs at Week 11 | 101 participants |
| Vehicle Gel | Complete Clearance of AKs at Week 11 | 80 participants |
Secondary
Partial Clearance of AKs at Week 11
Partial clearance of AKs at Week 11, defined as 75% or greater reduction from baseline in the number of clinically visible AKs in the selected treatment area at Week 11
Time frame: Week 11
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEP005 Gel, 0.015% | Partial Clearance of AKs at Week 11 | 130 participants |
| Vehicle Gel | Partial Clearance of AKs at Week 11 | 109 participants |
Secondary
Percentage Change From Baseline in Number of AKs at Week 11
Percentage change from baseline in number of AKs at Week 11
Time frame: Baseline to week 11
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PEP005 Gel, 0.015% | Percentage Change From Baseline in Number of AKs at Week 11 | 81.1 percentage of change | Standard Deviation 31.8 |
| Vehicle Gel | Percentage Change From Baseline in Number of AKs at Week 11 | 74.1 percentage of change | Standard Deviation 34.4 |