Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp

A Phase 2a, Open-Label, Multicenter, Activity and Safety Study of KX2-391 Ointment 1% in Subjects With Actinic Keratosis on the Face or Scalp

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02838628

Enrollment

168

Registered

2016-07-20

Start date

2016-04-11

Completion date

2017-12-22

Last updated

2021-04-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Actinic Keratosis

Brief summary

In this study, the activity, safety, and pharmacokinetics (PK) of KX2-391 Ointment was evaluated in adult participants with a clinical diagnosis of stable, clinically typical actinic keratosis (AK) on the face or scalp.

Detailed description

This study was an open-label, multicenter, activity, safety, tolerability, and PK study of KX2-391 Ointment administered topically to the face or scalp of participants with AK. The study consists of Screening, Treatment, and Follow-up Periods. Eligible participants were received 3 or 5 consecutive days of topical treatment, applied at the study site. Blood samples for PK analysis were collected. Activity (lesion counts) and safety evaluations were performed.

Interventions

DRUG50 mg of KX2-391 Ointment 1%

Dose: 50 mg; Route of administration: Topical

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Males and females ≥18 years old 2. Clinical diagnosis of stable, clinically typical actinic keratosis 3. A define treatment area on the face or scalp 4. Females must be postmenopausal, surgically sterile or otherwise incapable of pregnancy for at least 1 year; or must be using highly effective contraception for at least 90 days prior to treatment with KX2-391 Ointment 5. Males who have not had a vasectomy must agree to use barrier contraception 6. Participants who in the judgment of the Investigator, are in good general health 7. Willing to avoid excessive sun exposure 8. Able to comprehend and are willing to sign an informed consent form (ICF)

Exclusion criteria

1. Clinically atypical and/or rapidly changing AK lesions on the treatment area 2. Malignancy within 5 years prior to Screening except basal or squamous cell carcinoma not on the treatment area that were treated with curative intent and are without recurrence 3. Used any of retinoids at the most 90 days before Visit 1 glucocorticosteroids and methotrexate or other anti-metabolites within, at the most 28 days, before Visit 1 4. Used any topical therapies, treatments, or surgical or destructive modalities on the treatment area within, at the most 90 days, before Visit 1 5. Currently, or has experienced cutaneous malignancy, sunburn or body art on the treatment area within, at the most 180 days, before Visit 1 6. A history of sensitivity and/or allergy to any of the ingredients in the study medication 7. A skin disease or condition that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the participant to an unacceptable risk by study participation 8. 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 9. Females who are pregnant or nursing 10. Participated in an investigational drug trial during which an investigational study medication was administered within 14 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 Response of Actinic Keratosis	Day 57	Complete response rate was defined as the percentage of participants achieving 100% clearance in the treatment area on the face or scalp at Day 57.

Secondary

Measure	Time frame	Description
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57	Baseline, Days 8, 15, 29 and 57	Overall changes from baseline in actinic keratosis lesion counts has been reported.
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)	Baseline up to Day 57 (Treatment and follow-up period)	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational Product (IP). An AE did not necessarily have a causal relationship with the medicinal product. An SAE was defined as any untoward medical occurrence that at any dose, resulted in death, was life-threatening (i.e, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). TEAEs were defined as either those AEs with an onset after dosing or those pre-existing conditions that worsened after dosing. TEAEs included both serious and non-serious TEAEs.
Number of Participants With Any Treatment-emergent Adverse Events During Recurrence Follow-up Period	From Day 57 up to 12-months post-Day 57 (Recurrence follow-up period)	An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an IP. An AE did not necessarily have a causal relationship with the medicinal product. An SAE was defined as any untoward medical occurrence that at any dose, resulted in death, was life-threatening (i.e, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). TEAEs were defined as either those AEs with an onset after dosing or those pre-existing conditions that worsened after dosing. TEAEs included both serious and non-serious TEAEs.
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs)	Day 57	Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. Local skin reactions assessment included signs of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration on the treatment area. These signs were assessed using a 5-point grading scale ranging from 0 (not present) to 4 (worst), where (grade 0 = absent, grade 1 = slight, grade 2 = moderate, grade 3 = severe, grade 4 = very severe).
Number of Participants With Clinically Significant Abnormalities in Laboratory	Baseline to Day 57	Laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance was determined by the investigator.
Number of Participants With Clinically Significant Abnormalities in Vital Signs	Baseline 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.
Percentage of Participants With Partial Response of Actinic Keratosis	Day 57	Partial response rate was defined as the percentage of participants achieving more than or equal to 75% clearance in the treatment area on the face or scalp at Day 57.
Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE)	Baseline up to Day 57	A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.
Maximum Observed Plasma Concentration (Cmax) of KX2-391 of KX2-391	Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)	Cmax was defined as the maximum observed plasma concentration obtained directly from the concentration versus time curve.
Area Under the Plasma Concentration Time Curve From Time 0 to the Last Sampling Time (AUCt) of KX2-391	Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)	Area under the plasma concentration versus time curve from time zero to the last sampling time (t) at which the concentration is at or above the LLOQ. AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
Minimum Observed Plasma Concentration (Cmin) of KX2-391	Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)	Cmin was defined as minimum observed plasma concentration obtained directly from the concentration versus time curve.
Accumulation Ratio (R)	Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)	Ratio calculated from AUC and Cmax found on the last day of treatment and Day 1.
Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs)	Baseline 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.

Countries

United States

Participant flow

Recruitment details

This study was conducted at 16 sites in United States from 11 April 2016 to 22 December 2017.

Pre-assignment details

A total of 168 participants (84 each cohort) were enrolled and treated in this study. This study consisted of 2 periods, first was Treatment and Follow-up period (up to Day 57) and second was Recurrence follow-up period (12 months post-Day 57).

Participants by arm

Arm	Count
KX2-391 50 mg (Days 1 to 5) Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 5 consecutive days.	84
KX2-391 50 mg (Days 1 to 3) Participants were applied 50 mg of KX2-391 Ointment 1% topically on face or scalp in 25 cm\^2 treatment area, once daily for 3 consecutive days.	84
Total	168

Withdrawals & dropouts

Period	Reason	FG000	FG001
Recurrence Follow-up Period	Adverse Event	1	0
Recurrence Follow-up Period	AK Recurrence	18	13
Recurrence Follow-up Period	Non-compliance	0	1
Recurrence Follow-up Period	Other un-specified	1	1
Recurrence Follow-up Period	Withdrawal by Subject	0	2

Baseline characteristics

Characteristic	KX2-391 50 mg (Days 1 to 5)	KX2-391 50 mg (Days 1 to 3)	Total
Age, Continuous	69.0 Years STANDARD_DEVIATION 8.93	67.7 Years STANDARD_DEVIATION 8.32	68.3 Years STANDARD_DEVIATION 8.63
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	9 Participants	12 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants	75 Participants	156 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Number of AK Lesions	5.8 Lesions STANDARD_DEVIATION 1.41	5.4 Lesions STANDARD_DEVIATION 1.19	5.6 Lesions STANDARD_DEVIATION 1.32
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 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	84 Participants	83 Participants	167 Participants
Sex: Female, Male Female	8 Participants	12 Participants	20 Participants
Sex: Female, Male Male	76 Participants	72 Participants	148 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 84	0 / 84
other Total, other adverse events	37 / 84	19 / 84
serious Total, serious adverse events	4 / 84	3 / 84

Outcome results

Primary

Percentage of Participants With Complete Response of Actinic Keratosis

Complete response rate was defined as the percentage of participants achieving 100% clearance in the treatment area on the face or scalp at Day 57.

Time frame: Day 57

Population: Evaluable set included group of protocol-eligible participants who received 5 days (Cohort 1) or 3 days (Cohort 2) of study treatment and completed Day 1 and Day 57 AK lesion evaluations.

Arm	Measure	Value (NUMBER)
KX2-391 50 mg (Days 1 to 5)	Percentage of Participants With Complete Response of Actinic Keratosis	43 percentage of participants
KX2-391 50 mg (Days 1 to 3)	Percentage of Participants With Complete Response of Actinic Keratosis	32 percentage of participants

Secondary

Accumulation Ratio (R)

Ratio calculated from AUC and Cmax found on the last day of treatment and Day 1.

Time frame: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: PK Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

Arm	Measure	Value (MEAN)
KX2-391 50 mg (Days 1 to 5)	Accumulation Ratio (R)	NA ratio
KX2-391 50 mg (Days 1 to 3)	Accumulation Ratio (R)	NA ratio

Secondary

Area Under the Plasma Concentration Time Curve From Time 0 to the Last Sampling Time (AUCt) of KX2-391

Area under the plasma concentration versus time curve from time zero to the last sampling time (t) at which the concentration is at or above the LLOQ. AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.

Time frame: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: PK Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

Arm	Measure	Value (MEAN)
KX2-391 50 mg (Days 1 to 5)	Area Under the Plasma Concentration Time Curve From Time 0 to the Last Sampling Time (AUCt) of KX2-391	NA nanogramhour per milliliter (ngh/mL)
KX2-391 50 mg (Days 1 to 3)	Area Under the Plasma Concentration Time Curve From Time 0 to the Last Sampling Time (AUCt) of KX2-391	NA nanogramhour per milliliter (ngh/mL)

Secondary

Maximum Observed Plasma Concentration (Cmax) of KX2-391 of KX2-391

Cmax was defined as the maximum observed plasma concentration obtained directly from the concentration versus time curve.

Time frame: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: Pharmacokinetic (PK) Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

Arm	Measure	Value (MEAN)
KX2-391 50 mg (Days 1 to 5)	Maximum Observed Plasma Concentration (Cmax) of KX2-391 of KX2-391	NA nanograms/milliliter (ng/mL)
KX2-391 50 mg (Days 1 to 3)	Maximum Observed Plasma Concentration (Cmax) of KX2-391 of KX2-391	NA nanograms/milliliter (ng/mL)

Secondary

Minimum Observed Plasma Concentration (Cmin) of KX2-391

Cmin was defined as minimum observed plasma concentration obtained directly from the concentration versus time curve.

Time frame: Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Population: PK Analysis Set included the group of participants who received study treatment and completed at least one scheduled post-treatment PK evaluation.

Arm	Measure	Value (GEOMETRIC_MEAN)
KX2-391 50 mg (Days 1 to 5)	Minimum Observed Plasma Concentration (Cmin) of KX2-391	NA ng/mL
KX2-391 50 mg (Days 1 to 3)	Minimum Observed Plasma Concentration (Cmin) of KX2-391	NA ng/mL

Secondary

Number of Participants With Any Treatment-emergent Adverse Events During Recurrence Follow-up Period

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an IP. An AE did not necessarily have a causal relationship with the medicinal product. An SAE was defined as any untoward medical occurrence that at any dose, resulted in death, was life-threatening (i.e, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). TEAEs were defined as either those AEs with an onset after dosing or those pre-existing conditions that worsened after dosing. TEAEs included both serious and non-serious TEAEs.

Time frame: From Day 57 up to 12-months post-Day 57 (Recurrence follow-up period)

Population: Recurrence follow-up set included the group of participants who achieved complete clearance at Day 57.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
KX2-391 50 mg (Days 1 to 5)	Number of Participants With Any Treatment-emergent Adverse Events During Recurrence Follow-up Period	5 Participants
KX2-391 50 mg (Days 1 to 3)	Number of Participants With Any Treatment-emergent Adverse Events During Recurrence Follow-up Period	3 Participants

Secondary

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational Product (IP). An AE did not necessarily have a causal relationship with the medicinal product. An SAE was defined as any untoward medical occurrence that at any dose, resulted in death, was life-threatening (i.e, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). TEAEs were defined as either those AEs with an onset after dosing or those pre-existing conditions that worsened after dosing. TEAEs included both serious and non-serious TEAEs.

Time frame: Baseline up to Day 57 (Treatment and follow-up period)