A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)
Condition: Actinic Keratosis
MeSH terms: Keratosis, Actinic; Keratosis
Intervention: KX2-391 Ointment 1%; Placebo
Intervention description: Dose: 1% (250 mg single-use packets); Dosage form: Ointment; Route of administration: Topical; Dosage form: Ointment; Route of administration: Topical
Intervention MeSH terms: Tirbanibulin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study tested KX2-391 Ointment 1% against a placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: All Central Vendors and the sponsor were masked. The sponsor was unblind at the end of Day 57.
Enrollment: 351.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Actinic Keratosis; Keratosis; Keratosis, Actinic; Precancerous Conditions; Neoplasms; Sun Damaged Skin; Actinic Keratoses

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.
    

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.