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

• ClinicalTrials.gov Identifier: NCT02838628
• Recruitment Status: Completed
• First Posted: July 20, 2016
• Results First Posted: April 14, 2021
• Last Update Posted: April 14, 2021
• Sponsor: Almirall, S.A.
• Collaborator: Athenex, Inc.
• Information provided by (Responsible Party): Almirall, S.A.

Tracking Information

• First Submitted Date: July 18, 2016
• First Posted Date: July 20, 2016
• Results First Submitted Date: February 16, 2021
• Results First Posted Date: April 14, 2021
• Last Update Posted Date: April 14, 2021
• Actual Study Start Date: April 11, 2016
• Actual Primary Completion Date: January 11, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 19, 2021)

Percentage of Participants With Complete Response of Actinic Keratosis [ Time Frame: 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.

Original Primary Outcome Measures (submitted: July 18, 2016)

Complete response rate [ Time Frame: 57 Days ]

Activity will be evaluated by determining complete response rate. Complete response rate will be defined as the proportion of subjects achieving 100% complete clearance of all treated AK lesions on the face or scalp at Day 57.

Current Secondary Outcome Measures (submitted: March 19, 2021)

• Percentage of Participants With Partial Response of Actinic Keratosis [ Time Frame: 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.
• Overall Change From Baseline in Actinic Keratosis Lesion Counts at Day 8, 15, 29 and 57 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
• Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) [ Time Frame: 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.
• Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: July 18, 2016)

• Number of participants with abnormal laboratory values and/or adverse events that are related to treatment [ Time Frame: 15 Months ]
  Number of participants with abnormal laboratory values and/or adverse events that are related to treatment
• The amount of KX2-391 Ointment 1% in the blood stream [ Time Frame: 57 Days ]
  The measurement of KX2-391 Ointment levels in the blood stream over time

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp
• Official Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Actinic Keratosis

Intervention

Drug: 50 mg of KX2-391 Ointment 1%

Dose: 50 mg; Route of administration: Topical

Study Arms

• 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.
  Intervention: Drug: 50 mg of KX2-391 Ointment 1%
• 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.
  Intervention: Drug: 50 mg of KX2-391 Ointment 1%

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 15, 2019): 168
• Original Estimated Enrollment (submitted: July 18, 2016): 80
• Actual Study Completion Date: December 22, 2017
• Actual Primary Completion Date: January 11, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02838628
• Other Study ID Numbers: KX01-AK-002; U1111-1173-5677 ( Other Identifier: UTN )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Almirall, S.A.
• Original Responsible Party: Kinex Pharmaceuticals Inc.
• Current Study Sponsor: Almirall, S.A.
• Original Study Sponsor: Kinex Pharmaceuticals Inc.
• Collaborators: Athenex, Inc.

Investigators

• Study Chair: Jane Fang, MD; Kinex Pharmaceuticals Inc.

• PRS Account: Almirall, S.A.
• Verification Date: March 2021