Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Keratosis, Actinic

Keratosis

Exanthema

Skin Diseases

Precancerous Conditions

0.0025% PEP005 Topical Gel (Day 1,2 application)

PEP005

0.01% PEP005 Topical Gel (Day 1,2 application)

0.05% PEP005 Topical Gel (Day 1,2 application)

0.0025% PEP005 Topical Gel (Day 1,8 application)

0.01% PEP005 Topical Gel (Day 1,8 application)

0.05% PEP005 Topical Gel (Day 1,8 application)

Greg Siller

The purpose of this study is to determine whether topical application of PEP005 is safe for the treatment of actinic keratoses.

Study to Determine the Safety of Two Applications of PEP005 Topical Gel to Actinic Keratoses

A Multi-center, Randomized, Double-blind, Parallel-group, Vehicle-controlled Study to Determine the Safety of PEP005 0.0025%, 0.01% and 0.05% Gel With Two Treatment Schedules, Day 1 & 2 or Day 1 & 8 Applications to Actinic Keratoses

Peplin

Janelle Katsamas

Lawrence Anderson, Dr

Peter Welburn, PhD

Actinic keratoses (AK) is a common skin condition characterized by rough, scaly patches or sores on the top layer of the skin which if left untreated can progress to skin cancer. Current treatments can cause scarring and hypopigmentation, be inconvenient, or require long treatment duration. Non-invasive alternative therapy for treatment of AK lesions is thus being researched.

Study to Determine the Safety of PEP005 0.025% and 0.05% Topical Gel in Patients With Actinic Keratoses

A Multi-center, Randomized, Double-blind, Double-dummy, Vehicle-controlled Sequential Cohort Study to Determine the Safety PEP005 0.025% and 0.05% Topical Gel in Patients With Actinic Keratoses.

3-4 Watts applied locally for up to a 3 second burst to each AK lesion, repeated 3 times per lesion. Burst is defined as a single delivery of microwave energy. There will be approximately 20 seconds between each repeat dose.

Localized microwave energy applied to the distinct AK lesion. Each subject will receive treatment for a maximum of 2 visits (4-week interval between treatment).

For AK lesions assessed as "Thin" AK (Olsen Grades 1 and 2): Set at 3W and apply locally for up to a 3 second burst and adjust the dose and duration. Repeat on the same AK lesion as is tolerable for the subject (3 repetitions). There will be approximately 20 seconds between each repeat dose.

For AK lesions assessed as "Thick" AK (Olsen Grade 3): Set at 4W and apply locally for up to a 3 second burst and adjust the dose and duration. Repeat on the same AK lesion as is tolerable for the subject (3 repetitions).

As the AK lesions may be larger than 3mm in diameter, the dose administered to one AK lesion may require overlapping applications with the applicator tip. Ensure there is approximately 20 seconds between each repeat dose administered

Swift System

Emblation

Professor Dirschka

N Reith

S Strack

Dr Waibel

This is a randomized, controlled, multi-center trial in subjects diagnosed with Actinic Keratosis (AK) where each subject serves as their own control. The trial will be conducted at 2 sites, one in Germany and one in the United States. Approximately 60 subjects will be randomized to ensure 51 subjects complete the study.

The primary objective of this trial is to evaluate the efficacy of the Swift Microwave Treatment on resolution of Actinic Keratosis lesions.

The secondary objectives of this trial is to evaluate the efficacy, safety and tolerability of Swift Microwave treatment as a therapy for Actinic Keratosis (AK).

Eligible subjects who provide written informed consent and have 10, 12 or 14 distinct Actinic Keratosis lesions located on their scalp or hands will be randomized onto the study. Randomization of AK lesions will be stratified by side. Subjects will be randomized to treatment on half the number of AK lesions mapped located on their scalp or hands. The mapped AK lesions not randomized for treatment will receive no treatment (control).

The microwave energy applied by the Swift device will be applied to the randomized AK lesion sites for up to 2 treatments, spaced out by a 4-week interval. Follow-up is 2-months after the first treatment is administered where the AK lesions are assessed for resolution. Further follow-up visits occur at 4-months, 6-months and 12-months after the first treatment was administered where the AK lesions will be assessed for resolution or reoccurence.

This is an open label study, however, there is a blinded site investigator at each site who will not be aware of the AK lesions that are randomized to treatment. The blinded site investigator will assess resolution and reoccurrence of the AK lesions. Photos of the AK lesions will be taken and these will be reviewed by three independent blinded assessors to assess cosmetic outcomes.

Microwave Treatment for Actinic Keratosis

Pivotal Study to Assess the Clinical Efficacy and Safety of Microwave Treatment for Actinic Keratosis

Definition:

Treatment Success: complete clearance of ≥75% Actinic Keratosis lesions treated per subject, i.e., at least 75% of the AK lesions treated are fully cleared (not partially cleared).

AK Lesions classified as Not Present, AK I (Grade I mild), AK II (Grade II, moderate) or AK III (Grade III severe)

The subject is asked to rate the worst pain experienced during treatment as None, Mild, Moderate or Severe

The subject is asked to rate the worst pain experienced during the 10 minute period after treatment is completed as None, Mild, Moderate or Severe

For subjects who experienced pain after treatment, the subject is asked to rate the duration of pain experienced during the 10 minute period after treatment using the following time period scales: a few seconds, up to 1 minute, up to 2 minutes, up to 3 minutes, Still Sore.

Photographs of each treated and non-treated AK lesion will be assessed by the independent blinded assessors for cosmetic outcome as "excellent" (slight redness or pigmentation change), "good" (moderate redness or pigmentation change), "fair" (slight-to-moderate scarring, atrophy or induration), or "poor" (extensive scarring, atrophy or induration). Each assessment compares the photos taken at the current visit against the photos taken at the previous visit. The assessments by each independent blinded assessor is recorded separately.

At Baseline, the subject will be asked to rate how their AK lesions affect their daily activities, lifestyle and mood as: none, mild, moderate and severe.

At 6-months post first treatment, the subject will be asked to rate how their daily activities, lifestyle and mood are now affected, when compared to before study treatment as: significantly better, better, unchanged, worse, significantly worse.

The results at baseline and at 6 months post first treatment will be evaluated.

The DLQI questionnaire measures how the AK lesions have affected the subject's life over the past week. The score at baseline and at 6 months post first treatment will be evaluated.

The subject will be asked to rate the AK lesions that were treated compared to before treatment as: significantly better, better, unchanged, worse, significantly worse.

Emblation Limited

Blackwell Device Consulting

Lawrence Anderson, MD, F.A.C.P

The purpose of this study is :

* To determine the maximum tolerated dose (MTD) for PEP005 Topical Gel in patients with actinic keratoses.
* To evaluate patients for clinical safety
* To determine the systemic absorption of PEP005 Topical Gel

Actinic keratoses (AK) is a common skin condition characterized by rough, scaly patches or sores on the top layer of the skin which if left untreated can progress to skin cancer. Current treatments can cause scarring and hypopigmentation, be inconvenient, or require long treatment duration. Non-invasive alternative therapy for treatment of AK lesions is thus being researched.

This is an open label, dose escalation, cohort study to determine the maximum tolerated dose (MTD) of PEP005 Topical Gel, administered once daily for two consecutive days (90 ul gel applied topically over a 3 x 3cm template surrounding a target lesion), to patients with actinic keratoses (AK). The study will be conducted in one centre in the US. Three patients will be entered initially at the lowest dose level (0.01%) with up to an additional three patients to be entered in the event of a dose limiting toxicity (DLT) in the initial patients. DLT are defined as 'severe' local skin reactions observed by the Investigator, either prior to treatment on Day 2 ( following treatment on Day 1 ) or observed on Day 8 (following treatment on Day 2). Based on findings from phase I studies and the low systemic absorption found in non-clinical toxicokinetic evaluations, no systemic toxicity is anticipated.Once determined A total of 10 patients will be treated at the MTD in order to confirm it's determination. Based on findings from the phase I study, the starting dose will be 0.01% PEP005 Gel.

Secondary objectives of the study are (1) evaluate the clinical efficiency of PEP005 Topical Gel, when administered once daily for two consecutive days and (2) determine the systemic absorption of PEP005 Topical Gel at the MTD . Hematologic and biochemical assessments will be undertaken at the screening visit and at days 8 and 29 . Adverse events will be assessed at every study visit. Clinical response to treatment will be assessed at Days 8, 15 and 29.

Study to Determine the Maximum Tolerated Dose and Safety of PEP005 Topical Gel

An Open-label, Dose Escalation, Cohort Study to Determine the Maximum Tolerated Dose and Safety of PEP005 Topical Gel When Applied on Day 1 and Day 2 to Actinic Keratoses on the Shoulders, Chest, Back or Arms Followed by a Post-Treatment Follow-up Period Lasting at Four Weeks

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Anti-Infective Agents

Fluorouracil

Imiquimod

Diclofenac

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Immunomodulating Agents

Adjuvants, Immunologic

Interferons

Adults with actinic keratosis eligible to receive topical treatment with one of the four treatments

Topical field treatment as prescribed by dermatologist

Ingenol mebutate

5-fluorouracil

Study Director Study Director

This non-interventional, multinational study of topical field treatment of actinic keratosis (AK) aims to collect real-life experience with ingenol mebutate as well as one or two other topical field therapies commonly used in the individual country. Physicians will report baseline characteristics, while the main study focus will be on patient reported outcomes 3-4 weeks after treatment completion (treatment satisfaction, adherence, resource utilization and Health Related Quality of Life.

Dermatology centres in Denmark, Norway, Sweden, the Netherlands, the United Kingdom and Canada will participate.

Actinic keratosis (AK) is caused by exposure to UV radiation and has the potential to regress to normal skin or to squamous cell carcinoma. AK treatment options include cryotherapy for solitary lesions and topical field therapy or photodynamic therapy for lesions in an area of sun-damaged skin. This prospective, non-interventional, multinational study aims to describe and compare in a real-life setting the treatment satisfaction, treatment adherence, resource utilization and quality of life during topical field treatment of AK with 5-fluorouracil, imiquimod, diclofenac and ingenol mebutate.

Dermatology centres in Denmark, Sweden, Norway, Canada, the United Kingdom and the Netherlands will aim to include a total of approximately 1600 patients, of which around 100 in each country will be patients scheduled to receive treatment with ingenol mebutate. In each country patients will in addition be recruited for one or two of the other treatment arms, as appropriate in the country.

Only adult patients scheduled to start treatment with imiquimod, 5-fluorouracil, diclofenac or ingenol mebutate who have given informed consent to use data from their medical records for the study and to report study data themselves will be included and followed for the duration of the scheduled treatment + 3-4 weeks.

Physician will report patient demographics and AK characteristics at baseline. Patients will at baseline report AK Quality of Life, including general attitude regarding sun damaged skin at baseline, and, if applicable, treatment satisfaction and adherence with latest previous AK treatment. At 3-4 weeks after end of treatment, the patients will report treatment satisfaction, adherence, resource utilization, health related Quality of Life.

Treating physicians report drug-related Adverse Events in accordance with national laws and regulations and normal clinical practice.

The Real Life Topical Field Treatment of Actinic Keratosis Study

The Real Life Topical Field Treatment of Actinic Keratosis Study. An Observational Study Focusing on Patient Reported Outcomes

Treatment Satisfaction Questionnaire of Medication TSQM 9

Work Productivity and Activity Impairment Questionnaire

Occurrence and duration of redness of skin, dry skin, burning, or stinging

LEO Pharma

Dermatologic Agents

Aminolevulinic Acid

Methyl 5-aminolevulinate

WIthin each participant, two 50 cm2 adjacent test areas were randomized to laser or microdermabrasion pretreatment prior to daylight photodynamic therapy.

One 50 cm2 test area was randomized to pretreatment using a fractional 2940 nm Er:YAG laser (Joule®; Sciton Inc., Palo Alto, CA, USA). To remove hyperkeratosis, a fully-ablative 4 mm handpiece was optionally applied, followed by a single pass of a fractional Profrax 430 handpiece for all AKs. Subsequent field treatment consisted of a single pass of the Profrax 430 handpiece over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.

Ablative Fractional Carbon Dioxide (CO2) Laser

Another adjacent 50 cm2 test area was exposed to microdermabrasion using an MD pad with 58.5 µm-diameter particles (Ambu® Skin Prep Pads 2121M; Ambu A/S, Ballerup, Denmark). Lesion-directed treatment consisted of an increasing number of swipes concentrated to AK lesions. During field treatment, multiple swipes were applied in perpendicular directions over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.

Microdermabrasion

Merete Haedersdal, MD, Dr. Med

Comparison of treatment efficacy and safety of pretreatment with ablative fractional laser versus microdermabrasion combined with large-area photodynamic therapy with methyl aminolevulinate for actinic keratoses

For each study participant, two test areas (A and B) are demarcated in the same anatomical region, with each area containing no less than 5 actinic keratoses (AKs). Test areas are randomized to receive skin pretreatment of EITHER ablative fractional laser OR microdermabrasion prior to photodynamic therapy using methyl aminolevulinate.

Efficacy, local skin reactions and safety of both test areas are evaluated over a 12-15 week follow up period.

Laser and Microdermabrasion Before Photodynamic Therapy for Actinic Keratoses in Field-cancerized Skin

Pretreatment With Ablative Fractional Laser and Microdermabrasion Before Photodynamic Therapy for Actinic Keratoses in Field-cancerized Skin

Percentage clearance of baseline actinic keratoses (AKs), determined by the ratio of AK lesions that are clinically resolved 12-15 weeks after treatment compared to the AK number at baseline.

Number of new actinic keratoses (AKs) identified clinically 12-15 weeks after treatment and that were not present at the baseline evaluation.

Local skin reactions scale (min:0; better and max: 3; worse) used to grade each of the following parameters: erythema, edema, crusting, pustules, ulceration and scabbing, scaling.

The severity of each evaluated clinically on a 4-point scale where 0 = none, 1= mild, 2= moderate and 3= severe.

With 7 parameters the sum of all scores will produce a maximum composite score of 21.

Sun damage is evaluated clinically on a 4 point scale where 0 = none, 1= mild, 2= moderate and 3= severe sun damage.

Patient-reported pain during treatments is evaluated using the visual analog scale (VAS) where 0= no pain and 10= worst imaginable pain.

Side effects are evaluated over the course 12-15 weeks following treatment. In addition to unforeseen adverse events, specific side effects including the clinical presence of infection, scarring, hypopigmentation and hyperpigmentation are recorded.

Cosmetic appearance of treated areas is evaluated by investigators clinically (scores on a scale) using a 4-point scale where 0 = none, 1= acceptable, 2= good and 3= excellent outcome.

Cosmetic appearance is evaluated by patients at the end of the study (scores on a scale) using a 4 point scale where 0 = none, 1= acceptable, 2= good and 3= excellent

Patients were asked to report which pretreatment they preferred: Laser, microdermabrasion, or no preference

Galderma R&D

Bispebjerg Hospital

Professor and Senior Physician

Intra-individual design of 18 participants. "All study participants" are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).

Split-Person: Ablative Fractional Carbon Dioxide Laser or Microdermabrasion

Two 50 cm2 test areas (Test Area A and B) are demarcated on the skin of each study participant. One test area is randomized to receive the intervention: Ablative Fractional Carbon Dioxide (CO2) Laser prior to standard daylight photodynamic therapy. The other test area is randomized to receive the intervention: microdermabrasion prior to standard daylight photodynamic therapy.

Ablative Fractional Carbon Dioxide (CO2) Laser: Ablative Fractional Carbon Dioxide (CO2) Laser treatment is randomly allocated to one of two tests areas in each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy.

Microdermabrasion: Microdermabrasion (processing of the skin with a sandpaper-like material) is randomly allocated to one of two tests areas in each study participant. Microdermabrasion treatment consists of targeted treatment of actinic keratoses and field treatment of the entire test area. Afterwards, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area then undergoes 2 hours of daylight photodynamic therapy.

Split Person Design: Pretreatment With Ablative Fractional Carbon Dioxide Laser or Microdermabrasion

Age, Categorical

Age, Continuous

Sex: Female, Male

Denmark

Region of Enrollment

Each participant had two skin areas that individually were randomized to receive either microdermabrasion or ablative fractional laser prior to photodynamic therapy. Thus, with 18 participants, we had 36 test areas.

Emily Wenande

Ablative Fractional Laser

Intra-individual design of 18 participants. "All study participants" are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants received both inventions (18 test areas received AFL and 18 test areas received MD).

Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion

Percentage AK clearance in test areas receiving either AFL (18) or microdermabrasion (18) assisted daylight PDT treatment

Complete Clearance (%) of Actinic Keratoses (AKs)

New Actinic Keratoses (AKs)

Ablative Frational Laser

Two 50 cm2 test areas (Test Area A and B) are demarcated on the skin of each study participant. One test area is randomized to receive the intervention: Ablative Fractional Carbon Dioxide (CO2) Laser prior to standard daylight photodynamic therapy. The other test area is randomized to receive the intervention: microdermabrasion prior to standard daylight photodynamic therapy.

Ablative Fractional Carbon Dioxide (CO2) Laser: Ablative Fractional Carbon Dioxide (CO2) Laser treatment is randomly allocated to one of two tests areas in each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitizing agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy.

Pretreatment

Severity of Local Skin Reactions (LSRs)

Degree of Sun Damage

Treatment-related Pain

Treatment-related Side Effects

Investigator-reported Cosmesis (Clinical Evaluation)

Patient-reported Cosmesis

No Preference

Patient Pretreatment Preference

Intra-individual design. "All study participants" are grouped into a single arm. Two adjacent skin areas (test areas) on each participant was allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy.

Description of intervention: Ablative Fractional CO2 laser: CO2 laser treatment is randomly allocated to one of two tests areas within each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitizing agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy.

Microdermabrasion: Microdermabrasion (processing of the skin with a sandpaper-like material) is randomly allocated to one of two tests areas in each study participant. Microdermabrasion treatment consists of targeted treatment of actinic keratoses and field treatment of the entire test area. Afterwards, application of methyl aminolevulinate (MAL), a topical photosensitizing agent, is performed. The test area then undergoes 2 hours of daylight photodynamic therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Determine the Safety of Two Applications of PEP005 Topical Gel to Actinic Keratoses	NCT00107965	Actinic Keratos...	PEP005 PEP005 PEP005 PEP005 PEP005 PEP005 PEP005 PEP005	18 Years -	Peplin
Study to Determine the Safety of PEP005 0.025% and 0.05% Topical Gel in Patients With Actinic Keratoses	NCT00375739	Actinic Keratos...	PEP005	18 Years -	Peplin
Microwave Treatment for Actinic Keratosis	NCT05636800	Keratosis, Acti...	Swift System	18 Years - 85 Years	Blackwell Device Consulting
Study to Determine the Maximum Tolerated Dose and Safety of PEP005 Topical Gel	NCT00239135	Keratosis	PEP005	18 Years -	Peplin
Study to Determine the Safety of PEP005 0.025% and 0.05% Topical Gel in Patients With Actinic Keratoses	NCT00375739	Actinic Keratos...	PEP005	18 Years -	Peplin
The Real Life Topical Field Treatment of Actinic Keratosis Study	NCT02362152	Actinic Keratos...	Ingenol mebutat... 5-fluorouracil Imiquimod Diclofenac	18 Years -	LEO Pharma
Laser and Microdermabrasion Before Photodynamic Therapy for Actinic Keratoses in Field-cancerized Skin	NCT03006185	Actinic Keratos... Sun Damaged Ski... Solar Keratosis Solar Skin Dama...	Ablative Fracti... Microdermabrasi...	18 Years -	Bispebjerg Hospital

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