Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Skin Neoplasms

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Participants who have a history of squamous cell skin cancer (n=23) will be exposed to acute solar simulated light (SSL). Participants must have sun damage on the forearm, based on a standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36). Each subject will act as his/her own control to minimize inter-subject variability. Subjects from each cohort will be matched based on age and gender.

Participants without a history of squamous cell skin cancer (n=23) will be exposed to acute solar simulated light (SSL). Participants must have sun damage on the forearm, based on a standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36). Each subject will act as his/her own control to minimize inter-subject variability.

Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.

Solar Simulated Light

Stephanie Soto

UACC IIT

Clara Curiel-Lewandrowski, MD

The purpose of this research study is to look at how the proteins and genes in people's skin change when they're exposed to simulated sunlight. The researchers want to see if there are differences between people who've had skin cancer and those who haven't despite having a similar type of skin and history of sun exposure. Since this study is designed to simulate sun exposure to small areas of skin, mild to moderate sunburn and tanned spots at the site of the simulated sunlight exposure is a risk. In addition to simulated sun exposure, patients will also have four 6 mm punch skin biopsies performed. Brief discomfort may be felt when the local painkiller (lidocaine) is injected prior to skin biopsies; however, it is usually minimal. Participation in the study involves 4 visits to the clinic over the course of 4 weeks. Each visit will take no longer than 90 minutes.

SUV PDL1/PD1 in Sun Damaged & Sun Protected Human Skin of Participants

An Assessment of Acute Solar UV-induced PD-L1/PD1 Expression in Sun Damaged & Sun Protected Human Skin of Participants With and Without History of SCC

The primary objective will be the relative increase in PD-L1 protein expression levels in the epidermal keratinocytes of subjects in two risk cohorts (Cohort A (history of \> 2 cSCC) and Cohort B (no history of cSCC)) after acute solar simulated light treatment compared to unexposed skin within the same subject. Proteomic evaluation will be performed by reverse phase protein microarray and confirmatory IHC (immunohistochemistry) stain.

Reverse phase protein microarray will be implemented to evaluate changes in CD70/CD27 protein expression and immunohistochemistry assays will analyze changes in these signaling pathways over time.

Nanostring DSP (Digital Spatial Profiling). Whole transcriptomic analysis will assess these markers as well as query signaling pathways which may be differentially affected by UV in each group. The research team will perform NanoString spatial whole transcriptomic analysis on SD (sun damaged) skin samples in the 20 participants from each cohort by evaluating both pre- and post- SSL exposure, resulting in 2 matched pairs per study subject. The research team will also use DermTech RNA-seq for skin sampling and gene expression analysis on a subset of sun damaged skin samples.

The objective is to integrate the proteomic and genomic data to evaluate possible synergistic relationship between them in describing the risk of cSCC based on PD-L1/PD1 and other co-expressed genes/protein expression.

National Cancer Institute (NCI)

University of Arizona

Symptoms and General Pathology

Facies

Keratosis, Actinic

Keratosis

Precancerous Conditions

Skin Diseases

All Drugs and Chemicals

Tirbanibulin

Enzyme Inhibitors

KX2-391 Ointment was applied once daily for 5 consecutive days on the face or scalp.

The Vehicle Ointment was applied once daily for 5 consecutive days on the face or scalp.

Dose: 1% (250 mg single-use packets); Dosage form: Ointment; Route of administration: Topical

KX2-391 Ointment 1%

Dosage form: Ointment; Route of administration: Topical

Placebo

Jane Fang, MD

This Phase III study was designed to evaluate the efficacy and safety of KX2-391 Ointment 1% in adult participants when applied to an area of skin containing 4-8 stable, clinically typical actinic keratosis (AK) lesions on the face or scalp.

This study was a double-blinded, multicenter, efficacy, and safety study of KX2-391 ointment administered topically to the face or scalp of participants with AK.

The study consisted of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods. Eligible participants received up to 5 consecutive days of topical treatment. Efficacy (lesion counts) and safety evaluations were performed.

This study tested KX2-391 Ointment 1% against a placebo.

All Central Vendors and the sponsor were masked. The sponsor was unblind at the end of Day 57.

A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)

A Phase 3, Double-Blind, Vehicle-Controlled, Randomized, Parallel Group, Multicenter, Efficacy and Safety Study of KX2-391 Ointment 1% in Adult Subjects With Actinic Keratosis on the Face or Scalp

Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.

Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (\>=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.

Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).

Recurrence rate was estimated based on Kaplan-Meier method, with recurrence define as appearance of any AK lesions in the treatment area, including those recurred or newly identified.

Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. The LSR assessment was an Investigator's (or sub-investigator's) assessment of the following signs on the treatment area: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. The LSRs were graded on a 4-point scale ranging from 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense).

Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.

An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. TEAEs (serious and non-serious) were defined as either those AEs with onset after first dose or those pre-existing AEs that worsen after first dose. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.

An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.

Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.

Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.

A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.

ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. Clinical significance was determined by the investigator.

Athenex, Inc.

Almirall, S.A.

Safety population included all randomized participants who received at least one dose of study treatment.

Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm\^2 on face or scalp.

KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days in a treatment area of 25 cm\^2 on face or scalp.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Number of AK lesions at baseline

Intent-to-treat (ITT) population included all randomized participants.

Head of Global Clinical Development

Statistical significance in the study for Day 57 complete clearance rate was analyzed using a Cochran-Mantel-Haenszel model controlling for treatment location (face or scalp) and treatment group (Placebo versus KX2-391 Ointment 1%).

ITT population included all randomized participants.

Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions

Statistical significance in the study for Day 57 partial clearance rate was analyzed using a Cochran-Mantel-Haenszel model controlling for treatment location (face or scalp) and treatment group (Placebo versus KX2-391 Ointment 1%).

Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57

Day 8

Day 15

Day 29

Day 57

Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57

3 months post-Day 57

6 months post-Day 57

9 months post-Day 57

12 months post-Day 57

Recurrence follow-up population included all participants in the ITT Population who achieved complete clearance at the Day 57 visit. The recurrence rate was evaluated only for KX2-391 Ointment 1% arm, pre-specified in protocol.

Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57

Erythema-Grade 0

Erythema-Grade 1

Erythema-Grade 2

Erythema-Grade 3

Flaking/Scaling-Grade 0

Flaking/Scaling-Grade 1

Flaking/Scaling-Grade 2

Flaking/Scaling-Grade 3

Crusting-Grade 0

Crusting-Grade 1

Crusting-Grade 2

Crusting-Grade 3

Swelling-Grade 0

Swelling-Grade 1

Swelling-Grade 2

Swelling-Grade 3

Vesiculation/Pustulation-Grade 0

Vesiculation/Pustulation-Grade 1

Vesiculation/Pustulation-Grade 2

Vesiculation/Pustulation-Grade 3

Erosion/Ulceration-Grade 0

Erosion/Ulceration-Grade 1

Erosion/Ulceration-Grade 2

Erosion/Ulceration-Grade 3

Safety analysis set included participants who received at least one dose of study treatment.

Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)

Hypopigmentation: Baseline

Hypopigmentation: Day 5

Hypopigmentation: Day 8

Hypopigmentation: Day 15

Hypopigmentation: Day 29

Hypopigmentation: Day 57

Hyperpigmentation: Baseline

Hyperpigmentation: Day 5

Hyperpigmentation: Day 8

Hyperpigmentation: Day 15

Hyperpigmentation: Day 29

Hyperpigmentation: Day 57

Scarring: Baseline

Scarring: Day 5

Scarring: Day 8

Scarring: Day 15

Scarring: Day 29

Scarring: Day 57

Safety Population included all randomized participants who received at least one dose of study treatment.

Number of Participants With Pigmentation and Scarring in the Treatment Area

Participants with AE

Participants with any TEAE

Participants with any SAE

Participants with events of special interest

Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests

Participants with any AE

Recurrence follow-up population included all participants in the ITT Population who achieved complete clearance at the Day 57 visit.

Number of Participants With Adverse Events, Serious Adverse Events, Events of Special Interests Within the Treatment Area After Day 57 and up to 12 Months Post-Day 57

Hematology

Blood chemistry

Urinalysis

Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis

Number of Participants With Clinically Significant Safety Observations- Vital Signs

Number of Participants With Clinically Significant Safety Observations- Physical Examination

Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)

Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 centimeter square (cm\^2) on face or scalp.

Treatment and Response Assessment Period

Recurrence Follow-up Period

Participants will apply tirbanibulin 10 mg/g ointment once daily for 5 consecutive days beginning on Day 1. All participants will be evaluated for efficacy, safety, and tolerability at Day 8, 15, 29, and 57. Participants who do not achieve complete clearance (CC) at Day 57 will receive a second 5-day course of the treatment. Participants receiving a second treatment course will also be evaluated for efficacy, safety, and tolerability at Day 64, 71, and 85.

Participants will apply vehicle ointment once daily for 5 consecutive days beginning on Day 1. All participants will be evaluated for efficacy, safety, and tolerability at Day 8, 15, 29, and 57. Participants who do not achieve CC at Day 57 will receive a second 5-day course of the treatment. Participants receiving a second treatment course will also be evaluated for efficacy, safety, and tolerability at Day 64, 71, and 85.

Participants will apply tirbanibulin ointment topically on the face or balding scalp with AK.

Participants will apply vehicle ointment topically on the face or balding scalp with AK.

Vehicle ointment

Davide Carluccio

Ana Lucía Matamoros Díaz

The purpose of the study is to evaluate the efficacy and safety of tirbanibulin 10 milligrams per gram (mg/g) ointment when applied to a treatment field (TF) larger than 25 centimeter square (cm\^2) and up to 100 cm\^2 in adult participants with actinic keratosis (AK).

A Study to Evaluate the Efficacy and Safety of Tirbanibulin Ointment in Adult Participants With Actinic Keratosis

A Phase 3, Multicentre, Randomised, Double-blind, Vehicle-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Tirbanibulin 10 mg/g Ointment Applied to a Treatment Field Larger Than 25 cm^2 and up to 100 cm^2 in Adult Patients With Actinic Keratosis

Percentage change from baseline in the AK lesion count will be assessed.

PC is defined as proportion of participants achieving more than or equal to (\>=) 75 percent (%) clearance of AK lesions in the TF on the face or scalp at Day 57.

CC is defined as proportion of participants achieving 100 percent clearance of AK lesions in the TF on the face or scalp at Day 57.

Number of new lesions that are not present at baseline, occurring per participant in the TF at specific timepoints will be assessed.

Number of lesions per participant in the TF at specific timepoints will be assessed.

Skindex-16 is used for participants to rate skin conditions that have occurred within the previous week. It is a short 16-item patient-completed assessment that are classified into three domains: symptoms \[four items, 1-4\], emotions, \[seven items, 5-11\] and functioning \[five items, 12-16\]. All items are scored on a seven-point numerical analogue scales (0=never bothered to 6=always bothered). Each item is then transformed to a linear scale from 0 (never bothered) to 100 (always bothered), where higher the score = more severe in impairment. The total score is the average of all 16 items scores ranging from 0 \[best Health Related Quality of Life (HRQoL)\] to 96 (worst HRQoL), where higher score indicates worst quality of life.

Cosmetic Outcome is rated on a 4-point scale as excellent (no or mild redness or change in pigmentation), good (moderate redness or change in pigmentation), fair (slight-to-moderate scarring, atrophy, or induration), and poor (extensive scarring, atrophy, or induration).

The TSQM-14 is a participant-rated scale used to assess subjective satisfaction with medication. The TSQM-14 provided scores on 4 domains: effectiveness (questions 1 to 3) side effects (4 to 8), convenience (9 to 11), and global satisfaction (12 to 14). With the exception of item 4 (presence of side effects; yes or no), all items have five or seven responses, scored from one (least satisfied) to five or seven (most satisfied). Scores for each domain were transformed into a final score ranging from 0 to 100, with higher numbers indicating a higher level of satisfaction.

Local tolerability score is evaluated by the investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication is applied. These symptoms are assessed by using a 4-point scale of 0-3, where 0 (absent) and 3 (severe). The higher score indicates severe symptoms.

Maximum local tolerability score by treatment course for each individual sign (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. Local tolerability score for each signs are assessed by using a 4 - point scale of 0 - 3, where 0 = none and 3 = severe. The higher score indicates severe symptoms.

Time to maximum local tolerability score for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration will be assessed. Maximum local tolerability score by treatment course for each individual sign (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. Local tolerability score for each signs are assessed by using a 4 - point scale of 0 - 3, where 0 = none and 3 = severe. The higher score indicates severe symptoms.

Local tolerability signs composite score (0-18) at Specific Timepoints, defined as the sum of the scores graded from 0 (none) to 3 (severe) on all six individual tolerability sign categories (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. The higher score indicates severe symptoms.

Maximum local tolerability signs composite score (0-18) in treatment course, defined as the sum of the scores graded from 0 (none) to 3 (severe) on all six individual tolerability sign categories (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. The higher score indicates severe symptoms.

Time to maximum local tolerability signs composite score is observed in treatment course for each individual sign (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. Maximum local tolerability signs composite score (0-18) in treatment course, defined as the sum of the scores graded from 0 (none) to 3 (severe) on all six individual tolerability sign categories (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. The higher score indicates severe symptoms.

Absence or presence of pigmentation (that is, hypopigmentation and hyperpigmentation) and scarring in the TF will be assessed.

An AE is defined as any untoward medical occurrence in a clinical trial participant, regardless of the administration of the IMP and its causal relationship to it. unfavorable and unintended medical occurrence during the participant's participation in the trial, including deterioration of a pre-existing medical condition, an abnormal value in a laboratory assessment, or an abnormal finding in the physical examination. An SAE is any untoward medical occurrence that at any dose resulted in death; is life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in participant hospitalization; is congenital anomaly/birth defect or otherwise considered medically important. AESIs included skin cancers \[including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma\] appearing within or outside the TF during the study.

Number of participants with clinically significant laboratory abnormalities (included hematology, blood chemistry and urinalysis) will be assessed. Clinically Significant Abnormal values will be determined by the investigator.

Number of participants with vital signs (including measurement of systolic and diastolic blood pressure, heart rate, respiratory rate, and tympanic temperature) will be assessed. Abnormal values will be determined by the investigator.

Pharmaceutical Solutions

Dermatologic Agents

Aminolevulinic Acid

Photosensitizing Agents

Levulan® Kerastick® for Topical Solution will be applied to a designated area for 3 hours without occlusion prior to illumination with blue light using the standard FDA approved treatment time for the BLU-U device of 16 minutes 40 seconds.

Each subject will be randomized to undergo treatment to one side face and one dorsal forearm/hand treatment, while the other side will serve as untreated control. Treatments will be conducted at the beginning of study Day 1 (Initial Treatment), Day 30 after the initial treatment (+ 3 days), Day 180 after initial treatment (+ 30 days), 1 year after the initial treatment (+ 30 days), and every 6 months (+ 30 days) thereafter for 2 additional years.

Levulan® Kerastick® for Topical Solution will be applied to a designated area for 3 hours without occlusion prior to illumination with blue light

Levulan® Kerastick®

3 hours after Levulan® Kerastick® for Topical Solution is applied blue light illumination of designated area will be performed using the standard FDA approved treatment time of 16 minutes 40 seconds.

BLU-U Blue Light Photodynamic Therapy

Nathalie C. Zeitouni, MD

This is a pilot, phase 2, prospective, comparative study to evaluate the safety and efficacy of the combination of Levulan® Kerastick® for Topical Solution and blue light illumination using the BLU-U® Blue Light Photodynamic Therapy Illuminator (LevulanPDT).

The study hypothesis is that post solid organ transplantation patients, highly susceptible to non-melanoma skin cancer, can be treated safely and effectively through clinical cyclic application of PDT, lessening morbidity and possible mortality for this immunosuppressed patient population.

DUSA: Cyclic PDT for the Prevention of AK & NMSC in Solid Organ Transplant Recipients

Cyclic PDT for the Prevention of Actinic Keratosis and Non Melanoma Skin Cancer in Solid Organ Transplant Recipients

Number of AK will be counted for each site using the photographs of the treatment and the control areas. AKs will be graded by thickness.

Time to occurrence of AK will be calculated from the first visit to the development of an AK in the treatment areas and in the control areas.

Number of NMSC will be counted for each site using the photographs of the treatment and the control areas. NMSC, including basal cell carcinoma, Bowen's disease and squamous cell carcinoma, will be diagnosis and confirmed histologically by biopsy.

Time to occurrence of NMSC will be calculated from the first visit to the development of an NMSC in the treatment areas and in the control areas.

Pain will be assessed on the 10 point Visual Analogue Scale (VAS), as mild (0-3), moderate (4-7) or severe (8-10). Patients will be asked to rate the pain at the beginning, midway point (approximately 8 minutes later), and at the end of each PDT session.

The number of evaluable study participants who had a grade 3 or higher adverse event (AE) or any serious adverse event that's determined to be at least possibly or probably related to study treatment, or any AE which is at least possibly or probably related to study treatment that causes permanent study discontinuation.

DUSA Pharmaceuticals, Inc.

Medical Dermatology Specialists

Methyl 5-aminolevulinate

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SUV PDL1/PD1 in Sun Damaged & Sun Protected Human Skin of Participants	NCT06177106	Other Skin Chan...	Solar Simulated...	40 Years -	University of Arizona
A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)	NCT03285490	Actinic Keratos...	KX2-391 Ointmen... Placebo	18 Years -	Almirall, S.A.
SUV PDL1/PD1 in Sun Damaged & Sun Protected Human Skin of Participants	NCT06177106	Other Skin Chan...	Solar Simulated...	40 Years -	University of Arizona
A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)	NCT03285490	Actinic Keratos...	KX2-391 Ointmen... Placebo	18 Years -	Almirall, S.A.
A Study to Evaluate the Efficacy and Safety of Tirbanibulin Ointment in Adult Participants With Actinic Keratosis	NCT06135415	Keratosis, Acti...	Tirbanibulin Vehicle ointmen...	18 Years -	Almirall, S.A.
DUSA: Cyclic PDT for the Prevention of AK & NMSC in Solid Organ Transplant Recipients	NCT03110159	Skin Cancer Non-melanoma Sk... Sun Damaged Ski... Actinic Keratos...	Levulan® Kerast... BLU-U Blue Ligh...	18 Years -	Medical Dermatology Specialists
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

Spots Global Cancer Trial Database for sun damaged skin