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

Actinic Keratoses Clinical Trial

— AK003  

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: NCT03285477
• Other study ID #: KX01-AK-003
• Secondary ID: U1111-1191-8233
• Status: Completed
• Phase: Phase 3
• Start date: September 18, 2017
• Est. completion date: April 24, 2019

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 351
• Est. completion date: April 24, 2019
• Est. primary completion date: May 3, 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, 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

Related Conditions & MeSH terms

• Actinic Keratoses
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• Placebo
Vehicle Ointment was used in participants with Clinically typical AK on the face or scalp.
• KX2-391 Ointment 1%
The experimental drug, KX2-391 Ointment 1% was used in participants with Clinically typical AK on the face or scalp.

Locations

Country	Name	City	State
United States	Academic Dermatology Associates	Albuquerque	New Mexico
United States	Arlington Dermatology	Arlington Heights	Illinois
United States	ActivMed Practices & Research, Inc.	Beverly	Massachusetts
United States	Skin care Research, Inc	Boca Raton	Florida
United States	PMG Research of Cary	Cary	North Carolina
United States	OnSite Clinical Solutions, LLC	Charlotte	North Carolina
United States	CTI Clinical Research Center	Cincinnati	Ohio
United States	Olympian Clinical Research	Clearwater	Florida
United States	J&S Studies, Inc.	College Station	Texas
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey
United States	Deaconess Clinic Downtown	Evansville	Indiana
United States	Center For Dermatology Clinical Research	Fremont	California
United States	Minnesota Clinical Study Center	Fridley	Minnesota
United States	Advanced Research Associates	Glendale	Arizona
United States	Synexus US	Greer	South Carolina
United States	JDR Dermatology Research	Las Vegas	Nevada
United States	Coastal Clinical Research, Inc.	Mobile	Alabama
United States	DelRicht Research	New Orleans	Louisiana
United States	Mount Sinai Beth Israel	New York	New York
United States	Skin Specialists PC	Omaha	Nebraska
United States	Leavitt Medical Associates of Florida d/b/a Ameriderm Research	Ormond Beach	Florida
United States	Austin Institute for Clinical Research, Inc.	Pflugerville	Texas
United States	The Indiana Clinical Trials Center	Plainfield	Indiana
United States	Contour Dermatology	Rancho Mirage	California
United States	Skin Search of Rochester, Inc.	Rochester	New York
United States	Dermatology Research Center, Inc.	Salt Lake City	Utah
United States	Center for Clinical Studies	Webster	Texas
United States	Western States Clincial Research, Inc.	Wheat Ridge	Colorado
United States	PMG Research of Winston-Salem,LLC	Winston-Salem	North Carolina

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 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
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