Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp
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| ClinicalTrials.gov Identifier: NCT02838628 |
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Recruitment Status :
Completed
First Posted : July 20, 2016
Results First Posted : April 14, 2021
Last Update Posted : April 14, 2021
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Sponsor:
Almirall, S.A.
Collaborator:
Athenex, Inc.
Information provided by (Responsible Party):
Almirall, S.A.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Actinic Keratosis | Drug: 50 mg of KX2-391 Ointment 1% | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 168 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | April 11, 2016 |
| Actual Primary Completion Date : | January 11, 2017 |
| Actual Study Completion Date : | December 22, 2017 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: 50 mg of KX2-391 Ointment 1%
Dose: 50 mg; Route of administration: Topical |
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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.
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Drug: 50 mg of KX2-391 Ointment 1%
Dose: 50 mg; Route of administration: Topical |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Males and females ≥18 years old
- Clinical diagnosis of stable, clinically typical actinic keratosis
- A define treatment area on the face or scalp
- 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
- Males who have not had a vasectomy must agree to use barrier contraception
- Participants who in the judgment of the Investigator, are in good general health
- Willing to avoid excessive sun exposure
- Able to comprehend and are willing to sign an informed consent form (ICF)
Exclusion Criteria:
- Clinically atypical and/or rapidly changing AK lesions on the treatment area
- 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
- 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
- Used any topical therapies, treatments, or surgical or destructive modalities on the treatment area within, at the most 90 days, before Visit 1
- Currently, or has experienced cutaneous malignancy, sunburn or body art on the treatment area within, at the most 180 days, before Visit 1
- A history of sensitivity and/or allergy to any of the ingredients in the study medication
- 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
- 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
- Females who are pregnant or nursing
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02838628
Locations
| United States, California | |
| Center for Dermatology Clinical Research | |
| Fremont, California, United States, 94538 | |
| eStudy Site | |
| La Mesa, California, United States, 91942 | |
| Palmtree Clinical Research, Inc. | |
| Palm Springs, California, United States, 92262 | |
| United States, Colorado | |
| Horizons Clinical Research Center | |
| Denver, Colorado, United States, 80220 | |
| United States, Florida | |
| Clinical Research of South Florida | |
| Coral Gables, Florida, United States, 33134 | |
| International Dermatology Research | |
| Miami, Florida, United States, 33144 | |
| Compass Research | |
| Orlando, Florida, United States, 32806 | |
| Forward Clinical Trials, Inc. | |
| Tampa, Florida, United States, 33624 | |
| Palm Beach Research Center | |
| West Palm Beach, Florida, United States, 33409 | |
| United States, Minnesota | |
| Minnesota Clinical Study Center | |
| Fridley, Minnesota, United States, 55432 | |
| United States, South Carolina | |
| Dermatology and Laser Center of Charleston | |
| Charleston, South Carolina, United States, 29414 | |
| United States, Tennessee | |
| Institute of Clinical Research - Tennessee, LLC | |
| Murfreesboro, Tennessee, United States, 37130 | |
| United States, Texas | |
| J&S Studies, Inc. | |
| College Station, Texas, United States, 77845 | |
| The Center for Skin Research | |
| Houston, Texas, United States, 77056 | |
| Clinical Trials of Texas, Inc. | |
| San Antonio, Texas, United States, 78229 | |
| Dermatology Clinical Research Center | |
| San Antonio, Texas, United States, 78229 | |
Sponsors and Collaborators
Almirall, S.A.
Athenex, Inc.
Investigators
| Study Chair: | Jane Fang, MD | Kinex Pharmaceuticals Inc. |
Study Documents (Full-Text)
Documents provided by Almirall, S.A.:
Documents provided by Almirall, S.A.:
Study Protocol [PDF] September 26, 2016
Statistical Analysis Plan [PDF] August 1, 2018
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Almirall, S.A. |
| ClinicalTrials.gov Identifier: | NCT02838628 |
| Other Study ID Numbers: |
KX01-AK-002 U1111-1173-5677 ( Other Identifier: UTN ) |
| First Posted: | July 20, 2016 Key Record Dates |
| Results First Posted: | April 14, 2021 |
| Last Update Posted: | April 14, 2021 |
| Last Verified: | March 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Keratosis, Actinic Keratosis Skin Diseases Precancerous Conditions |
Neoplasms Tirbanibulin Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |