A Multi-Center Study to Evaluate the Efficacy and Safety of KX01 Ointment 1% on Actinic Keratosis on Face or Scalp

Study Overview
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Brief Summary
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This Phase III study is designed to evaluate the efficacy and safety of KX01 Ointment in adult participants when applied to an area of skin containing more than 1, clinically typical Actinic Keratosis (AK) lesions on the face or scalp.

Detailed Description
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This study is a double-blinded, multicenter, activity, and safety study of KX01 Ointment administered topically to the face or scalp of participants with actinic keratosis. The study consists of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods. Eligible participants received 5 consecutive days of topical treatment, to be applied at the study site. Activity (lesion counts) and safety evaluations is performed.

Official Title
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A Phase 3, Double-Blind, Vehicle-Controlled, Randomized, Parallel Group, Multicenter, Efficacy, Safety and PK Study of KX01 Ointment 1% in Japanese Adult Subjects With Actinic Keratosis on the Face or Scalp

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: KX01 ointment 1%
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese Males and females ≥20 years old A treatment area on the face or scalp that: is a contiguous area measured 25 cm2 contains more than 1 clinically typical, visible, and discrete AK lesions Subjects who, in the judgment of the Investigator or Sub-investigator, are in good general health based on: medical history physical examination (PE) findings vital signs clinical chemistry, hematology, and urinalysis results Females must be postmenopausal (>45 years of age with at least 12 months of amenorrhea), surgically sterile (by hysterectomy, bilateral oophorectomy, or tubal ligation); or, women with childbearing potential must use highly effective contraception for at least 30 days or 1 menstrual cycle, whichever is longer, prior to study treatment and must agree to continue to use highly effective contraception for at least 30 days following their last dose of study treatment. Highly effective contraception includes oral hormonal contraceptives, hormonal contraceptive implant, injection or patch, intrauterine device, or complete abstinence from sexual intercourse. Sexually active males who have not had a vasectomy and whose partner is reproductively capable must agree to use barrier contraception from Screening until 90 days after their last dose of study treatment. All subjects must agree not to donate sperm or eggs or attempt conception from Screening until 90 days following their last dose of study treatment. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 prior to randomization. Willing to avoid excessive sunlight or ultraviolet (UV) light exposure, including the use of tanning beds, to the face or scalp Exclusion Criteria: Clinically atypical and / or rapidly changing AK lesions on the treatment area, e.g., hypertrophic, hyperkeratotic, recalcitrant disease (had cryosurgery on two previous occasions) and / or cutaneous horn Location of the treatment area is: On any location other than the face or scalp Within 5 cm of an incompletely healed wound Within 5 cm of a suspected basal cell carcinoma (BCC) or SCC Been previously treated with KX01 Ointment Anticipated need for in-patient hospitalization or in-patient surgery from Day 1 to Day 57 Treatment with 5-fluorouracil (5-FU), imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other treatments for AK within the treatment area or within 2 cm of the treatment area, within 8 weeks prior to the Screening visit Use of the following therapies and / or medications within 2 weeks prior to the Screening visit: Cosmetic or therapeutic procedures (e.g., use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) within the treatment area or within 2 cm of the selected treatment area Acid-containing therapeutic products (e.g., salicylic acid or fruit acids, such as alpha- and beta-hydroxyl acids and glycolic acids), topical retinoids, or light chemical peels within the treatment area or within 2 cm of the selected treatment area Topical salves (non-medicated / non-irritant lotion and cream are acceptable) or topical steroids within the treatment area or within 2 cm of the selected treatment area; artificial tanners within the treatment area or within 5 cm of the selected treatment area Use of the following therapies and / or medications within 4 weeks prior to the Screening visit: Treatment with immunomodulators (e.g., azathioprine), cytotoxic drugs (e.g., cyclophosphamide, vinblastine, chlorambucil, methotrexate), or interferons / interferon inducers

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study tests KX01 Ointment 1% against a placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KX01 Ointment 1%<br>KX01 Ointment 1% is applied topically once daily for 5 consecutive days on face or scalp | Drug: KX01 ointment 1%<br>* The experimental drug, KX01 Ointment 1% is used in participants with Clinically typical AK on the face or scalp.<br>|
| Placebo Comparator: Placebo<br>Vehicle Ointment is applied topically once daily for 5 consecutive days on face or scalp | Drug: Placebo<br>* Vehicle Ointment is used in participants with Clinically typical AK on the face or scalp.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with complete (100%) clearance of Actinic Keratosis (AK) lesions | Complete clearance rate is defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area. | Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Clearance Rate of AK Lesions at Day 57 | Partial clearance rate of AK lesions is defined as the proportion of subjects on Day 57 with a ≥ 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area. | Day 57 | 
| Recurrence rate of AK lesions in subjects who achieved complete clearance at Day 57 | For subjects who achieve 100% clearance of AK lesions in the treatment area on Day 57, a Investigator or Sub-investigator will perform a count of clinically visible AK lesions (lesion count) during the Recurrence Follow-up Period at the 3-, 6-, 9- and 12-month visits. In principle, the Investigator or Sub-investigator performing the lesion count should be the same Investigator or Sub-investigator who evaluated the subject previously during the study. | 3, 6, 9 and 12 months post-Day 57 | 
| Number of participants with local skin reactions (LSR) in the treatment area | At Baseline (Day 1 predose), LSRs on the treatment area will be assessed by the Investigator or Sub-investigator. The same Investigator or Sub-investigator will conduct the LSR assessment at all visits for an individual subject. LSR signs on the treatment area include the following: erythema, flaking / scaling, crusting, swelling, vesiculation / pustulation, and erosion / ulceration. These signs will be assessed using a 4-point grading scale. | Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57 | 
| Number of participants with pigmentation and scarring in the treatment area | At the time of LSR assessment, hypo- and hyper-pigmentation and scarring on the treatment area will be assessed by the Investigator or Sub-investigator as being present or absent. Pigmentation and scarring will be assessed at Baseline (Day 1 predose). In principle, the same Investigator or Sub-investigator will assess pigmentation and scarring at all visits for an individual subject. | Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57 | 
| Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs), events of special interest |  | From Baseline (Day 1 predose) up to Day 57 | 
| Number of participants with AEs within the treatment area after Day 57 up to 12 months post-Day 57 |  | After Day 57 up to 12 months post-Day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic Keratosis, Skin disease