Clinical trial NCT03285477: A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Actinic Keratoses
Keywords: Actinic Keratosis
Keratosis
Keratosis, Actinic
Skin Diseases
Actinic Keratoses
Precancerous Conditions
Neoplasms
Lead sponsor: Almirall, S.A.
Sponsor class: INDUSTRY
Collaborators: name: Athenex, Inc.
First posted: 2017-09-18
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study tested KX2-391 Ointment 1% against a placebo.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions
timeFrame: Day 57
Secondary outcomes:
measure: Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57
timeFrame: Day 57
measure: Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57
timeFrame: Days 8, 15, 29 and 57
measure: Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57
timeFrame: 3, 6, 9 and 12 months post-Day 57
measure: Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)
timeFrame: Day 57
measure: Number of Participants With Pigmentation and Scarring in the Treatment Area
timeFrame: Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57
measure: Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests
timeFrame: Baseline (Day 1 predose) up to Day 57
measure: 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
timeFrame: From Day 57 up to 12-months post-Day 57
measure: Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis
timeFrame: From Baseline (Day 1 predose) up to Day 57
measure: Number of Participants With Clinically Significant Safety Observations- Vital Signs
timeFrame: From Baseline (Day 1 predose) up to Day 57
measure: Number of Participants With Clinically Significant Safety Observations- Physical Examination
timeFrame: From Baseline (Day 1 predose) up to Day 57
measure: Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)
timeFrame: From Baseline (Day 1 predose) up to Day 57
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc.
state: Alabama
city: Glendale
country: United States
facility: Advanced Research Associates
state: Arizona
city: Fremont
country: United States
facility: Center For Dermatology Clinical Research
state: California
city: Rancho Mirage
country: United States
facility: Contour Dermatology
state: California
city: Wheat Ridge
country: United States
facility: Western States Clincial Research, Inc.
state: Colorado
city: Boca Raton
country: United States
facility: Skin care Research, Inc
state: Florida
city: Clearwater
country: United States
facility: Olympian Clinical Research
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Ormond Beach
country: United States
facility: Leavitt Medical Associates of Florida d/b/a Ameriderm Research
state: Florida
city: Arlington Heights
country: United States
facility: Arlington Dermatology
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic Downtown
state: Indiana
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center
state: Indiana
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Beverly
country: United States
facility: ActivMed Practices & Research, Inc.
state: Massachusetts
city: Fridley
country: United States
facility: Minnesota Clinical Study Center
state: Minnesota
city: Omaha
country: United States
facility: Skin Specialists PC
state: Nebraska
city: Las Vegas
country: United States
facility: JDR Dermatology Research
state: Nevada
city: East Windsor
country: United States
facility: Psoriasis Treatment Center of Central New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: Academic Dermatology Associates
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: Rochester
country: United States
facility: Skin Search of Rochester, Inc.
state: New York
city: Cary
country: United States
facility: PMG Research of Cary
state: North Carolina
city: Charlotte
country: United States
facility: OnSite Clinical Solutions, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem,LLC
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Greer
country: United States
facility: Synexus US
state: South Carolina
city: College Station
country: United States
facility: J&S Studies, Inc.
state: Texas
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research, Inc.
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies
state: Texas
city: Salt Lake City
country: United States
facility: Dermatology Research Center, Inc.
state: Utah
Study officials:
affiliation: Athenex, Inc.
name: Jane Fang, MD
role: STUDY_CHAIR
References:
citation: 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.