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

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.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: 50 mg of KX2-391 Ointment 1%

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.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fremont, California, United States, 94538
      • Center for Dermatology Clinical Research
    • La Mesa, California, United States, 91942
      • eStudy Site
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research, Inc.
  • Colorado
    • Denver, Colorado, United States, 80220
      • Horizons Clinical Research Center
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Miami, Florida, United States, 33144
      • International Dermatology Research
    • Orlando, Florida, United States, 32806
      • Compass Research
    • Tampa, Florida, United States, 33624
      • Forward Clinical Trials, Inc.
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Clinical Study Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Dermatology and Laser Center of Charleston
  • Tennessee
    • Murfreesboro, Tennessee, United States, 37130
      • Institute of Clinical Research - Tennessee, LLC
  • Texas
    • College Station, Texas, United States, 77845
      • J&S Studies, Inc.
    • Houston, Texas, United States, 77056
      • The Center for Skin Research
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78229
      • Dermatology Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: KX2-391 50 mg (Days 1 to 5); Participants were applied 50 milligrams (mg) of KX2-391 Ointment 1% topically on face or scalp in 25 centimeter square (cm^2) treatment area, once daily for 5 consecutive days.	Drug: 50 mg of KX2-391 Ointment 1%; Dose: 50 mg; Route of administration: Topical
EXPERIMENTAL: 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.	Drug: 50 mg of KX2-391 Ointment 1%; Dose: 50 mg; Route of administration: Topical

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Partial Response of Actinic Keratosis	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.	Day 57
Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57	Overall changes from baseline in actinic keratosis lesion counts has been reported.	Baseline, Days 8, 15, 29 and 57
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.	Baseline up to Day 57 (Treatment and follow-up period)
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.	From Day 57 up to 12-months post-Day 57 (Recurrence follow-up period)
Number of Participants With Maximal Post Baseline Local Skin Reactions (LSRs)	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).	Day 57
Number of Participants With Clinically Significant Abnormalities in Laboratory	Laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance was determined by the investigator.	Baseline to Day 57
Number of Participants With Clinically Significant Abnormalities in 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.	Baseline up to Day 57
Number of Participants With Clinically Significant Abnormalities in 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.	Baseline up to Day 57
Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE)	A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.	Baseline up to Day 57
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.	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 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.	Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)
Minimum Observed Plasma Concentration (Cmin) of KX2-391	Cmin was defined as minimum observed plasma concentration obtained directly from the concentration versus time curve.	Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)
Accumulation Ratio (R)	Ratio calculated from AUC and Cmax found on the last day of treatment and Day 1.	Pre-dose, 0.5, 1 and 4 hours post-dose on Days 1, 3 (Cohort 2) and 5 (Cohort 1)

Collaborators and Investigators

• Sponsor: Almirall, S.A.
• Collaborators: Athenex, Inc.
• Investigators: Study Chair: Jane Fang, MD, Kinex Pharmaceuticals Inc.

Publications and helpful links

General Publications

• Kempers S, DuBois J, Forman S, Poon A, Cutler E, Wang H, Cutler D, Fang J, Kwan R. Tirbanibulin Ointment 1% as a Novel Treatment for Actinic Keratosis: Phase 1 and 2 Results. J Drugs Dermatol. 2020 Nov 1;19(11):1093-1100. doi: 10.36849/JDD.2020.5576.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 11, 2016
• Primary Completion (ACTUAL): January 11, 2017
• Study Completion (ACTUAL): December 22, 2017

Study Registration Dates

• First Submitted: July 18, 2016
• First Submitted That Met QC Criteria: July 18, 2016
• First Posted (ESTIMATE): July 20, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 14, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tirbanibulin
• Other Study ID Numbers: KX01-AK-002; U1111-1173-5677 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No