OQL011, Dose I, ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2)

OQL011, Dose II, ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2)

OQL011, Dose III, ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2)

Vehicle ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2)

OQL011 is an ointment containing active ingredient.

OQL011

Vehicle ointment is an ointment containing no active ingredient.

Vehicle Ointment

Mario E. Lacouture, MD

Hand-Foot Skin Reaction (HFSR) is a common adverse event induced by Vascular Endothelial Growth Receptor Inhibitor (VEGFRi) treatment in cancer patients. The main purpose of this study is to evaluate the safety and efficacy of OQL011 compared to vehicle ointment in treating patients with moderate to severe VEGFRi-associated HFSR. This study will also identify an optimal dosage for Phase III study and explore the pharmacokinetics profile of OQL011 in HFSR patients.

A Study to Investigate OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients

A Phase II Study to Evaluate the Safety and Efficacy of OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients

There is no plan to make individual participant data (IPD) available to other researchers.

The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.

HF-QoL questionnaire is comprised of a 20-item symptom domain and an 18-item daily activity domain. Each item is rated on a 5-point scale from 0 (not at all) to 4 (always or extremely) during the previous week. The HF-QoL symptom and daily activity total scores are transformed to a scale of 0 to 100, based on the sum of each unit-weighted item score divided by the maximum score. Higher scores on the HF-QoL indicate worse quality of life or greater symptom burden. (refer to R. T. Anderson et al., The Oncologist 2015;20:831-838)

The subject records pain associated with HFSR using 100 mm VAS ranging from "no pain" at 0 mm to "unbearable pain" at 100 mm on the paper VAS.

The subject records pain associated with HFSR using score 0 to 10 ranging from "no pain" for Score 0 to "unbearable pain" for Score 10.

OnQuality Pharmaceuticals (USA) LLC

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Keratosis, Actinic

Keratosis

Precancerous Conditions

Skin Diseases

All Drugs and Chemicals

Tirbanibulin

Enzyme Inhibitors

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Investigate OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients	NCT04088318	Hand-Foot Skin ...	OQL011 Vehicle Ointmen...	18 Years -	OnQuality Pharmaceuticals (USA) LLC
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.
A Study to Investigate OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients	NCT04088318	Hand-Foot Skin ...	OQL011 Vehicle Ointmen...	18 Years -	OnQuality Pharmaceuticals (USA) LLC

Spots Global Cancer Trial Database for vehicle ointment