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

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

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.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: KX01 ointment 1%; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • Toho University Medical Center Sakura Hospital
  • Fukuoka, Japan
    • Kiryu Dermatology Clinic
  • Fukuoka, Japan
    • Tomoko Matsuda dermatology Clinic
  • Kagawa, Japan
    • Takamatsu Red Cross Hospital
  • Kagoshima, Japan
    • Hashiguchi Dermatology
  • Kagoshima, Japan
    • Katahira Dermatology and Urology
  • Kanagawa, Japan
    • National Hospital Organization Sagamihara National Hospital
  • Kanagawa, Japan
    • Nippon Medical School Musashi Kosugi Hospital
  • Kumamoto, Japan
    • Kumamoto University Hospital
  • Kumamoto, Japan
    • Noguchi Dermatology Clinic
  • Kumamoto, Japan
    • Suizenji Dermatology Clinic
  • Miyazaki, Japan
    • Futaba Dermatology and Skin Surgery Clinic
  • Miyazaki, Japan
    • Toyama Hifuka
  • Okayama, Japan
    • Okayama Saiseikai Outpatient Center Hospital
  • Osaka, Japan
    • Medical Corporation Ayumi Sakurakai Dermatology Ophthalmology Kume Clinic
  • Osaka, Japan
    • Mochidahifuka
  • Tokyo, Japan
    • Juntendo University Hospital
  • Tokyo, Japan
    • Ntt Medical Center Tokyo
  • Toyama, Japan
    • Toyama Prefectural Central Hospital
  • Yamanashi, Japan
    • University of Yamanashi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Japanese Males and females ≥20 years old

2. A treatment area on the face or scalp that:

   1. is a contiguous area measured 25 cm2
   2. contains more than 1 clinically typical, visible, and discrete AK lesions

3. Subjects who, in the judgment of the Investigator or Sub-investigator, are in good general health based on:

   1. medical history
   2. physical examination (PE) findings
   3. vital signs
   4. clinical chemistry, hematology, and urinalysis results
4. 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.
5. 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.
6. 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.
7. 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.
8. Willing to avoid excessive sunlight or ultraviolet (UV) light exposure, including the use of tanning beds, to the face or scalp

Exclusion Criteria:

1. 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

2. 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
3. Been previously treated with KX01 Ointment
4. Anticipated need for in-patient hospitalization or in-patient surgery from Day 1 to Day 57
5. 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

6. 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

7. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PharmaEssentia
• Collaborators: PharmaEssentia Japan K.K.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Actual): November 20, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Actinic Keratosis; Skin disease
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: B21-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No