A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp (AK003)

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

This Phase III study is designed to evaluate the efficacy and safety of KX2-391 Ointment 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.

Study Overview

• Status: Completed
• Conditions: Actinic Keratoses
• Intervention / Treatment: Drug: Placebo; Drug: KX2-391 Ointment 1%

Detailed Description

This study was a double-blinded, multicenter, activity, and safety study of KX2-391 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 was performed.

• Study Type: Interventional
• Enrollment (Actual): 351
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Advanced Research Associates
  • California
    • Fremont, California, United States, 94538
      • Center for Dermatology Clinical Research
    • Rancho Mirage, California, United States, 92270
      • Contour Dermatology
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Western States Clincial Research, Inc.
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Skin Care Research, Inc
    • Clearwater, Florida, United States, 33756
      • Olympian Clinical Research
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Ormond Beach, Florida, United States, 32174
      • Leavitt Medical Associates of Florida d/b/a Ameriderm Research
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Arlington Dermatology
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Deaconess Clinic Downtown
    • Plainfield, Indiana, United States, 46168
      • The Indiana Clinical Trials Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Research
  • Massachusetts
    • Beverly, Massachusetts, United States, 01915
      • ActivMed Practices & Research, Inc.
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Clinical Study Center
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Skin Specialists PC
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • JDR Dermatology Research
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Psoriasis Treatment Center of Central New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Academic Dermatology Associates
  • New York
    • New York, New York, United States, 10013
      • Mount Sinai Beth Israel
    • Rochester, New York, United States, 14623
      • Skin Search of Rochester, Inc.
  • North Carolina
    • Cary, North Carolina, United States, 27511
      • PMG Research of Cary
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem,LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Synexus US
  • Texas
    • College Station, Texas, United States, 77845
      • J&S Studies, Inc.
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research, Inc.
    • Webster, Texas, United States, 77598
      • Center for Clinical Studies
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Dermatology Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Males and females greater than or equal to (≥) 18 years old
2. A defined area on the face or scalp contains 4 to 8 clinically typical, visible, and discrete AK lesions
3. Participants who in the judgment of the Investigator, are in good general health
4. Females must be postmenopausal [greater than (>) 45 years of age with at least 12 months of amenorrhea], surgically sterile (by hysterectomy, bilateral oophorectomy, or tubal ligation); or, if of childbearing potential, must be using 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 through 90 days after their last dose of study treatment.
6. All participants must agree not to donate sperm or eggs or attempt conception from Screening through 90 days following their last dose of study treatment
7. Willing to avoid excessive sun or UV exposure
8. Able to comprehend and are willing to sign the informed consent form (ICF).

Exclusion Criteria

1. Clinically atypical and/or rapidly changing AK lesions on the treatment area

2. Location of the selected 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 squamous cell carcinoma (SCC)
3. Been previously treated with KX2-391 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 (eg, 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 (eg, 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 (eg, azathioprine), cytotoxic drugs (eg, cyclophosphamide, vinblastine, chlorambucil, methotrexate) or interferons/interferon inducers
   • Treatment with systemic medications that suppress the immune system (eg, cyclosporine, prednisone, methotrexate, alefacept, infliximab)
8. Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene) within 6 months prior to the Screening visit
9. A history of sensitivity and/or allergy to any of the ingredients in the study medication
10. A skin disease (eg, atopic dermatitis, psoriasis, eczema) or condition (eg, scarring, open wounds) that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the participants to unacceptable risk by study participation
11. Other significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the Investigator, would expose the participant to unacceptable risk by study participation
12. Females who are pregnant or nursing
13. Participated in an investigational drug trial during which an investigational study medication was administered within 30 days or 5 half-lives of the investigational product, whichever is longer, before dosing

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
Placebo Comparator: Placebo; Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp	Drug: Placebo; Vehicle Ointment was used in participants with Clinically typical AK on the face or scalp.
Experimental: KX2-391 Ointment 1%; KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp	Drug: KX2-391 Ointment 1%; The experimental drug, KX2-391 Ointment 1% was 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 was 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
Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57	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.	Day 57
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57	Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).	Days 8, 15, 29 and 57
Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57	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.	3, 6, 9 and 12 months post-Day 57
Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)	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).	Day 57
Number of Participants With Pigmentation and Scarring in the Treatment Area	Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.	Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57
Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests	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.	Baseline (Day 1 predose) up to Day 57
Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis	Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.	From Baseline (Day 1 predose) up to Day 57
Number of Participants With Clinically Significant Safety Observations- Vital Signs	Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.	From Baseline (Day 1 predose) up to Day 57
Number of Participants With Clinically Significant Safety Observations- Physical Examination	A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.	From Baseline (Day 1 predose) up to Day 57
Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)	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.	From Baseline (Day 1 predose) up to Day 57
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	An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the 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.	From Day 57 up to 12-months post-Day 57

Collaborators and Investigators

• Sponsor: Almirall, S.A.
• Collaborators: Athenex, Inc.
• Investigators: Study Chair: Jane Fang, MD, Athenex, Inc.

Publications and helpful links

General Publications

• Blauvelt A, Kempers S, Lain E, Schlesinger T, Tyring S, Forman S, Ablon G, Martin G, Wang H, Cutler DL, Fang J, Kwan MR; Phase 3 Tirbanibulin for Actinic Keratosis Group. Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis. N Engl J Med. 2021 Feb 11;384(6):512-520. doi: 10.1056/NEJMoa2024040.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2017
• Primary Completion (Actual): May 3, 2018
• Study Completion (Actual): April 24, 2019

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Neoplasms; Actinic Keratosis; Actinic Keratoses; Skin Diseases; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tirbanibulin
• Other Study ID Numbers: KX01-AK-003; U1111-1191-8233 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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