A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)

Actinic Keratosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03285490
• Other study ID #: KX01-AK-004
• Secondary ID: U1111-1191-8287
• Status: Completed
• Phase: Phase 3
• Start date: September 15, 2017
• Est. completion date: April 24, 2019

Study information

• Verified date: February 2021
• Source: Almirall, S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 351
• Est. completion date: April 24, 2019
• Est. primary completion date: May 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Actinic Keratosis
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• KX2-391 Ointment 1%
Dose: 1% (250 mg single-use packets); Dosage form: Ointment; Route of administration: Topical
• Placebo
Dosage form: Ointment; Route of administration: Topical

Locations

Country	Name	City	State
United States	DermResearch	Austin	Texas
United States	Study Protocol, Inc	Boynton Beach	Florida
United States	Laser & Skin Surgery Center of Indiana	Carmel	Indiana
United States	Clinical Research Center of the Carolinas	Charleston	South Carolina
United States	Aventiv Research Inc.	Dublin	Ohio
United States	Hamzavi Dermatology	Fort Gratiot	Michigan
United States	AboutSkin Dermatology	Greenwood Village	Colorado
United States	Henderson Dermatology Research	Henderson	Nevada
United States	Burke Pharmaceutical Research	Hot Springs	Arkansas
United States	Suzanne Bruce and Associates, P.A., The Center for Skin Research	Houston	Texas
United States	Dawes Fretzin Clinical Research Group	Indianapolis	Indiana
United States	Dermatology Associates Of Knoxville, PC	Knoxville	Tennessee
United States	Clinical Trials of SWLA, LLC	Lake Charles	Louisiana
United States	DS Research	Louisville	Kentucky
United States	The Education & Research Foundation, Inc.	Lynchburg	Virginia
United States	Sweet Hope Research Specialty, Inc.	Miami Lakes	Florida
United States	Dermatology Specialists, Inc.	Murrieta	California
United States	Union Square Laser Dermatology	New York	New York
United States	Dermatology Specialists, Inc.	Oceanside	California
United States	Alliance Dermatology	Phoenix	Arizona
United States	Oregon Medical Research Center	Portland	Oregon
United States	Activmed Practices & Research, Inc	Portsmouth	New Hampshire
United States	Medisearch Clinical Trials	Saint Joseph	Missouri
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Skin Surgery Medical Group, Inc.	San Diego	California
United States	Synexus	Santa Rosa	California
United States	Dermatology Associates of Seattle	Seattle	Washington
United States	Rivergate Dermatology Clinical Research	Springfield	Tennessee
United States	Forward Clinical Trials, Inc.	Tampa	Florida
United States	Synexus US	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Almirall, S.A.	Athenex, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 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. 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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