Actinic Keratoses
Conditions
Keywords
Actinic Keratosis, Keratosis, Keratosis, Actinic, Skin Diseases, Actinic Keratoses, Precancerous Conditions, Neoplasms
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.
Interventions
DRUGPlacebo
Vehicle Ointment was used in participants with Clinically typical AK on the face or scalp.
The experimental drug, KX2-391 Ointment 1% was used in participants with Clinically typical AK on the face or scalp.
Sponsors
Athenex, Inc.
Almirall, S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All Central Vendors and the sponsor were masked. The sponsor was unblind at the end of Day 57.
Intervention model description
This study tested KX2-391 Ointment 1% against a placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions | Day 57 | Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | 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). |
| Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57 | 3, 6, 9 and 12 months post-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. |
| Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Day 57 | 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). |
| Number of Participants With Pigmentation and Scarring in the Treatment Area | Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57 | Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed. |
| Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Baseline (Day 1 predose) up to 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. 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. |
| Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57 | 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. |
| Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis | From Baseline (Day 1 predose) up to Day 57 | Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator. |
| Number of Participants With Clinically Significant Safety Observations- Vital Signs | From Baseline (Day 1 predose) up to Day 57 | Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator. |
| Number of Participants With Clinically Significant Safety Observations- Physical Examination | From Baseline (Day 1 predose) up to Day 57 | A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator. |
| Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs) | From Baseline (Day 1 predose) up to Day 57 | 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. |
| 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 | From Day 57 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 31 sites in United States from 18 September 2017 to 24 April 2019.
Pre-assignment details
A total of 351 participants were enrolled in the study, 176 participants were randomized to the Vehicle control (121 face, 55 scalp treatment) and 175 participants were randomized to KX2-391 Ointment 1 percent (%) (119 face, 56 scalp treatment).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp | 176 |
| KX2-391 Ointment 1% KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp | 175 |
| Total | 351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Recurrence Follow-up Period | AK recurrence during the Recurrence Follow-Up Period | 5 | 51 |
| Recurrence Follow-up Period | Lost to Follow-up | 0 | 1 |
| Recurrence Follow-up Period | Withdrawal of consent | 1 | 3 |
| Treatment and Response Assessment Period | Death | 1 | 0 |
| Treatment and Response Assessment Period | Withdrawn of Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | KX2-391 Ointment 1% | Total |
|---|---|---|---|
| Age, Continuous | 70.2 years STANDARD_DEVIATION 9.41 | 69.5 years STANDARD_DEVIATION 8.55 | 69.9 years STANDARD_DEVIATION 8.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 171 Participants | 173 Participants | 344 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of AK Lesions | 5.9 Lesions STANDARD_DEVIATION 1.35 | 5.8 Lesions STANDARD_DEVIATION 1.28 | 5.8 Lesions STANDARD_DEVIATION 1.31 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 175 Participants | 175 Participants | 350 Participants |
| Sex: Female, Male Female | 22 Participants | 28 Participants | 50 Participants |
| Sex: Female, Male Male | 154 Participants | 147 Participants | 301 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 176 | 0 / 175 |
| other Total, other adverse events | 62 / 176 | 68 / 175 |
| serious Total, serious adverse events | 2 / 176 | 1 / 175 |
Outcome results
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.
Time frame: Day 57
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions | 5 percentage of participants |
| KX2-391 Ointment 1% | Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions | 44 percentage of participants |
Comparison: Statistical significance in the study for Day 57 complete clearance rate was analyzed using a Cochran-Mantel-Haenszel model controlling for treatment location (face or scalp) and treatment group (Placebo versus KX2-391 Ointment 1%).p-value: <0.0001Cochran-Mantel-Haenszel
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.
Time frame: Baseline (Day 1 predose) up to Day 57
Population: Safety analysis population included all randomized participants who received at least one dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with AE | 62 Participants |
| Placebo | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with any TEAE | 57 Participants |
| Placebo | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with SAE | 2 Participants |
| Placebo | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with events of special interest | 4 Participants |
| KX2-391 Ointment 1% | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with events of special interest | 5 Participants |
| KX2-391 Ointment 1% | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with AE | 66 Participants |
| KX2-391 Ointment 1% | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with SAE | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests | Participants with any TEAE | 57 Participants |
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.
Time frame: From Day 57 up to 12-months post-Day 57
Population: Recurrence Follow-up Population includes participants achieved complete clearance at the Day 57 visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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 | Participants with any AE | 0 Participants |
| Placebo | 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 | Participants with any SAE | 0 Participants |
| Placebo | 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 | Participants with events of special interest | 0 Participants |
| KX2-391 Ointment 1% | 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 | Participants with any AE | 4 Participants |
| KX2-391 Ointment 1% | 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 | Participants with any SAE | 1 Participants |
| KX2-391 Ointment 1% | 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 | Participants with events of special interest | 0 Participants |
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.
Time frame: From Baseline (Day 1 predose) up to Day 57
Population: Safety analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs) | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs) | 0 Participants |
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.
Time frame: From Baseline (Day 1 predose) up to Day 57
Population: Safety Population included all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis | Hematology | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis | Blood chemistry | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis | Urinalysis | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis | Hematology | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis | Blood chemistry | 1 Participants |
| KX2-391 Ointment 1% | Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis | Urinalysis | 3 Participants |
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.
Time frame: From Baseline (Day 1 predose) up to Day 57
Population: Safety analysis population included all randomized participants who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Safety Observations- Physical Examination | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Clinically Significant Safety Observations- Physical Examination | 0 Participants |
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.
Time frame: From Baseline (Day 1 predose) up to Day 57
Population: Safety analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Safety Observations- Vital Signs | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Clinically Significant Safety Observations- Vital Signs | 0 Participants |
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).
Time frame: Day 57
Population: Safety analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 2 | 14 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 1 | 84 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 2 | 11 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 0 | 72 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 1 | 90 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 0 | 81 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 0 | 140 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 1 | 33 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 2 | 3 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 0 | 163 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 1 | 12 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 2 | 1 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 0 | 174 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 1 | 2 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 2 | 0 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 3 | 0 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 0 | 168 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 1 | 8 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 2 | 0 Participants |
| Placebo | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 3 | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 2 | 5 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 0 | 6 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 0 | 107 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 1 | 48 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 2 | 2 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 2 | 116 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 1 | 55 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erythema-Grade 3 | 5 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 1 | 15 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 0 | 16 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 2 | 12 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 1 | 70 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 3 | 1 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 2 | 78 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Swelling-Grade 3 | 1 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Flaking/Scaling-Grade 3 | 11 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 3 | 0 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 0 | 84 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 0 | 158 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 1 | 69 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Erosion/Ulceration-Grade 0 | 155 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 2 | 20 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Vesiculation/Pustulation-Grade 1 | 14 Participants |
| KX2-391 Ointment 1% | Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) | Crusting-Grade 3 | 2 Participants |
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.
Time frame: Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57
Population: Safety analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 15 | 7 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 5 | 19 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 8 | 21 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 15 | 23 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 29 | 23 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: 57 | 20 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Baseline | 27 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 5 | 24 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 8 | 23 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 15 | 26 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 29 | 25 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 57 | 23 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Baseline | 10 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 5 | 8 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 29 | 7 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 57 | 7 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 8 | 9 Participants |
| Placebo | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Baseline | 21 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 5 | 8 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Baseline | 21 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 15 | 20 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 5 | 11 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 15 | 8 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 8 | 10 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 29 | 18 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 15 | 12 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 57 | 7 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: Day 29 | 17 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 57 | 12 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hypopigmentation: 57 | 13 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 29 | 9 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Baseline | 22 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Baseline | 12 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 5 | 18 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Scarring: Day 8 | 7 Participants |
| KX2-391 Ointment 1% | Number of Participants With Pigmentation and Scarring in the Treatment Area | Hyperpigmentation: Day 8 | 17 Participants |
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).
Time frame: Days 8, 15, 29 and 57
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 8 | 0.0 lesion count |
| Placebo | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 15 | 0.0 lesion count |
| Placebo | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 29 | -1.0 lesion count |
| Placebo | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 57 | -1.0 lesion count |
| KX2-391 Ointment 1% | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 57 | -5.0 lesion count |
| KX2-391 Ointment 1% | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 8 | -1.0 lesion count |
| KX2-391 Ointment 1% | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 29 | -4 lesion count |
| KX2-391 Ointment 1% | Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 | Day 15 | -4.0 lesion count |
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.
Time frame: Day 57
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57 | 16 percentage of participants |
| KX2-391 Ointment 1% | Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57 | 68 percentage of participants |
Comparison: Statistical significance in the study for Day 57 partial clearance rate was analyzed using a Cochran-Mantel-Haenszel model controlling for treatment location (face or scalp) and treatment group (Placebo versus KX2-391 Ointment 1%).p-value: <0.0001Cochran-Mantel-Haenszel
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.
Time frame: 3, 6, 9 and 12 months post-Day 57
Population: Recurrence Follow-up Population includes participants achieved complete clearance at the Day 57visit. The recurrence rate was evaluated only for KX2-391 Ointment 1% arm, pre-specified in protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57 | 3 Months Post-Day 57 | 33 percentage of participants |
| Placebo | Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57 | 6 Months Post-Day 57 | 30 percentage of participants |
| Placebo | Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57 | 9 Months Post-Day 57 | 33 percentage of participants |
| Placebo | Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57 | 12 months Post-Day 57 | 18 percentage of participants |