Clinical trial NCT03285490: A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)
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 Keratosis
Keywords: Actinic Keratosis
Keratosis
Keratosis, Actinic
Precancerous Conditions
Neoplasms
Sun Damaged Skin
Actinic Keratoses
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 was designed to evaluate the efficacy and safety of KX2-391 Ointment 1% 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, efficacy, and safety study of KX2-391 ointment administered topically to the face or scalp of participants with AK.

The study consisted of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods. Eligible participants received up to 5 consecutive days of topical treatment. Efficacy (lesion counts) and safety evaluations were 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, were in good general health.
4. Females were 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, were using highly effective contraception for at least 30 days or 1 menstrual cycle, whichever was longer, prior to study treatment and agreed 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 had not had a vasectomy, and whose partner was reproductively capable, must had agreed to use barrier contraception from Screening through 90 days after their last dose of study treatment.
6. All participants must had agreed 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 ultraviolet exposure.
8. Able to comprehend and were 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 centimeters (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 (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 (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 were 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 (e.g., atopic dermatitis, psoriasis, eczema) or condition (e.g., scarring, open wounds) that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the participant 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 were 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 was 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: Phoenix
country: United States
facility: Alliance Dermatology
state: Arizona
city: Tucson
country: United States
facility: Synexus US
state: Arizona
city: Hot Springs
country: United States
facility: Burke Pharmaceutical Research
state: Arkansas
city: Murrieta
country: United States
facility: Dermatology Specialists, Inc.
state: California
city: Oceanside
country: United States
facility: Dermatology Specialists, Inc.
state: California
city: San Diego
country: United States
facility: Skin Surgery Medical Group, Inc.
state: California
city: Santa Rosa
country: United States
facility: Synexus
state: California
city: Greenwood Village
country: United States
facility: AboutSkin Dermatology
state: Colorado
city: Boynton Beach
country: United States
facility: Study Protocol, Inc
state: Florida
city: Miami Lakes
country: United States
facility: Sweet Hope Research Specialty, Inc.
state: Florida
city: Tampa
country: United States
facility: Forward Clinical Trials, Inc.
state: Florida
city: Carmel
country: United States
facility: Laser & Skin Surgery Center of Indiana
state: Indiana
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group
state: Indiana
city: Louisville
country: United States
facility: DS Research
state: Kentucky
city: Lake Charles
country: United States
facility: Clinical Trials of SWLA, LLC
state: Louisiana
city: Fort Gratiot
country: United States
facility: Hamzavi Dermatology
state: Michigan
city: Saint Joseph
country: United States
facility: Medisearch Clinical Trials
state: Missouri
city: Henderson
country: United States
facility: Henderson Dermatology Research
state: Nevada
city: Portsmouth
country: United States
facility: Activmed Practices & Research, Inc
state: New Hampshire
city: New York
country: United States
facility: Union Square Laser Dermatology
state: New York
city: Dublin
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Portland
country: United States
facility: Oregon Medical Research Center
state: Oregon
city: Charleston
country: United States
facility: Clinical Research Center of the Carolinas
state: South Carolina
city: Knoxville
country: United States
facility: Dermatology Associates Of Knoxville, PC
state: Tennessee
city: Springfield
country: United States
facility: Rivergate Dermatology Clinical Research
state: Tennessee
city: Austin
country: United States
facility: DermResearch
state: Texas
city: Houston
country: United States
facility: Suzanne Bruce and Associates, P.A., The Center for Skin Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Lynchburg
country: United States
facility: The Education & Research Foundation, Inc.
state: Virginia
city: Seattle
country: United States
facility: Dermatology Associates of Seattle
state: Washington
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.