KX01 Ointment Phase 1 Study in Patients With Plaque Type Psoriasis

A Phase 1, Dose Escalation Trial to Evaluate the Safety, Tolerability and Activity of Topical Administrations of Three Different Strengths of KX01 Ointment in Patients With Plaque Type Psoriasis

This is a Phase I dose escalation study to assess the safety, tolerability and activity of three different strengths of topical KX01 in the treatment of patients with plaque-type psoriasis.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: KX01 0.01% (0.1 mg/g); Drug: KX01 0.1% (1.0 mg/g); Drug: KX01 1% (10 mg/g) for 5 days; Drug: KX01 1% (10 mg/g) for consecutive 5 days and 2 days rest for 1 cycle, and repeat up to 4 cycles; Drug: Placebo

Detailed Description

This is a Phase I dose escalation study to assess the safety, tolerability and activity of three different strengths of topical KX01 (Tirbanibulin Ointment) in the treatment of patients with plaque-type psoriasis. The study will be performed in four stages as below.

Stage I: 6 patients (KX01 0.01% [0.1 mg/g]) + 2 patients (placebo); Stage II: 6 patients (KX01 0.1% [1.0 mg/g] + 2 patients (placebo); Stage III: 6 patients (KX01 1% [10 mg/g]) for 5 days; Stage IV: 6 patients (KX01 1% [10 mg/g]), duration escalation for up to 4 cycles.

If there's no major safety concern in the previous stage with an unanimous consent by the sponsor and the principle investigator, the study proceeded to the next stage.

The primary objective is to evaluate the safety and tolerability of three different strengths of KX01 ointment in patients with plaque-type psoriasis. The secondary objective is to gain evidence regarding the activity of three different strengths of KX01 ointment in patients with plaque-type psoriasis.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patients with plaque-type psoriasis, 20 years and older.
• Patient has a confirmed diagnosis of chronic plaque-type psoriasis for at least six months. For stage 4, PGA should be ≧3 &≦5 at baseline.
• A single lesion of ≥ 16 square centimetre and ≤ 625 square centimetre in size for Stage 1 and 2, and ≥ 16 square centimetre and ≤ 100 square centimetre in size for Stage 3 and 4 are selected as the target lesion (assessed at screening and Day 1).
• Medical history, vital signs, physical examination, standard 12-lead ECG and laboratory investigations have to be clinically insignificant or within laboratory reference ranges for the relevant laboratory tests, unless the investigator consider the deviation for out of range values to be irrelevant for the purpose of the study.
• No other disorders that, in the investigator's opinion, will prevent the patient from safely participating in this study or interfere with the evaluation of the patient's psoriasis.
• Patient is able to discontinue the use of any systemic medication or therapy for psoriasis.
• For females, either of the following conditions will be met: 1. Not of childbearing potential: Surgically sterilized, undergone a hysterectomy, amenorrhea for ≥ 12 months and considered post-menopausal; 2. Of childbearing potential: Negative serum pregnancy test at screening and not lactating, Either abstaining from sexual activity, or have to agree to use an accepted method of contraception, and agree to continue with the same method throughout the study.
• Male patients with partners of childbearing potential have to be willing to use contraception during the study and three months after end of treatment and is not to donate sperm for the duration of the study and for 3 months thereafter.
• Patient have to be able to provide written informed consent prior to the initiation of any study related procedures and able to comply with all the requirements of the study.

Exclusion Criteria:

• History of hypersensitivity to the investigational medicinal product (IMP) or to medicinal products with similar chemical structures.
• Presence of a skin disorder other than psoriasis in the target areas to be evaluated, including forms of inflammatory or non-inflammatory skin disorders that might interfere with determining efficacy or tolerability of the IMP.
• Severe forms of psoriasis or forms of psoriasis other than plaque psoriasis.
• All systemic psoriasis medications, including psoralens and ultraviolet A radiation treatments or other systemic immunosuppressive medication, are not allowed within five half-lives or 4 weeks (whichever is longer) prior to the first administration of the IMP.
• The use of topical therapies for psoriasis, including ultraviolet light B, on the target lesion to be studied within two weeks prior to the first administration of the IMP.
• Previous treatment with anti-tumor necrosis factor/interleukin (IL)-12/IL-23 or any other monoclonal antibodies within three months prior to the first administration of the IMP.
• Presence or history of any clinically significant acute or chronic disease which could interfere with the patient's participation or study outcome and at discretion of the clinical investigator.
• Patient with drug-induced psoriasis and is unable to discontinue the causal agent(s).
• Patient using prescription or non-prescription systemic drugs (e.g. vitamins and dietary, herbal supplements, paracetamol, aspirin or non-steroidal anti-inflammatory drugs [NSAIDs]) that might have an effect on psoriasis and is unable to maintain the stable dose or discontinue the dose during the study period.
• Participation in another study with an experimental drug, where the last administration of the previous IMP is within 4 weeks (or within five elimination half-lives for chemical entities or two elimination half-lives for antibodies or insulin, whichever is longer) before administration of IMP in this study, at the discretion of the investigator.
• A positive serum pregnancy test (beta human chorionic gonadotropin) or lactation.
• Vulnerable patients, e.g. persons in detention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KX01 0.01% in stage I; Six patients in the stage 1 will receive KX01 0.01% (0.1 mg/g) for 2 weeks, followed by 1-week wash-out, another 2-week treatment, and then 2-week follow-up.	Drug: KX01 0.01% (0.1 mg/g); Stage 1: 6 patients (KX01 0.01% [0.1 mg/g])
Placebo Comparator: Placebo in stage 1; Two patients in the stage 1 will receive placebo treatment for 2 weeks, followed by 1-week wash-out, another 2-week treatment, and then 2-week follow-up.	Drug: Placebo; Contains same excipients with KX01 but do not contain Tirbanibulin
Experimental: KX01 0.1% in stage 2; Six patients in the stage 2 will receive KX01 0.1% (1.0 mg/g) for 4 weeks, followed by 2-week follow-up.	Drug: KX01 0.1% (1.0 mg/g); Stage 2: 6 patients (KX01 0.1% [1.0 mg/g])
Placebo Comparator: Placebo in stage 2; Two patients in the stage 2 will receive placebo treatment for 4 weeks, followed by 2-week follow-up.	Drug: Placebo; Contains same excipients with KX01 but do not contain Tirbanibulin
Experimental: KX01 1% for 5 days in stage 3; Six patients in stage 3 will receive 1% KX01 (10 mg/g) once daily for consecutive 5 days and then receive post-treatment follow-up on Day 6, 15 and 29.	Drug: KX01 1% (10 mg/g) for 5 days; Stage 3: 6 patients (KX01 1% [10 mg/g]) for 5 days
Experimental: KX01 1% for consecutive 5 days and 2 days rest for 1 cycle, and repeat up to 4 cycles in stage 4; Six patients in stage 4 will be treated with daily KX01 1% (10 mg/g) ointment for consecutive 5 days and 2 days rest for 1 cycle, and repeat up to 4 cycles. And post-treatment follow-up visits will be conducted 14 days (Follow-up visit 1) and 28 days (Follow-up visit 2) after the end of cycle 4 treatment.	Drug: KX01 1% (10 mg/g) for consecutive 5 days and 2 days rest for 1 cycle, and repeat up to 4 cycles; Stage 4: 6 patients (KX01 1% [10 mg/g])for consecutive 5 days and 2 days rest for 1 cycle, and repeat up to 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event at Stage 1	Incidence of adverse event	Day 50
Adverse event at Stage 2	Incidence of adverse event	Day 43
Adverse event at Stage 3	Incidence of adverse event	Day 29
Adverse event at Stage 4	Incidence of adverse event	28 days after the end of cycle 4 treatment (each cycle is 7 days)
Local tolerability score at Stage 1	4-point (0-3) rating scale; higher scores mean a worse outcome	Day 50
Local tolerability score at Stage 2	4-point (0-3) rating scale; higher scores mean a worse outcome	Day 43
Local tolerability score at Stage 3	4-point (0-3) rating scale; higher scores mean a worse outcome	Day 29
Local tolerability score at Stage 4	4-point (0-3) rating scale; higher scores mean a worse outcome	28 days after the end of cycle 4 treatment (each cycle is 7 days)
Vital signs at Stage 1	any abnormal vital sign with clinical significance	Day 50
Vital signs at Stage 2	any abnormal vital sign with clinical significance	Day 43
Vital signs at Stage 3	any abnormal vital sign with clinical significance	Day 29
Vital signs at Stage 4	any abnormal vital sign with clinical significance	28 days after the end of cycle 4 treatment (each cycle is 7 days)
12-lead ECG at Stage 1	any abnormal finding of 12-lead ECG with clinical significance	Day 36
12-lead ECG at Stage 2	any abnormal finding of 12-lead ECG with clinical significance	Day 29
12-lead ECG at Stage 3	any abnormal finding of 12-lead ECG with clinical significance	Day 29
12-lead ECG at Stage 4	any abnormal finding of 12-lead ECG with clinical significance	28 days after the end of cycle 4 treatment (each cycle is 7 days)
Hematology assessments at Stage 1	any abnormal hematologic lab data with clinical significance	Day 36
Clinical chemistry assessments at Stage 1	any abnormal chemical lab data with clinical significance	Day 36
Urinalysis assessments at Stage 1	any abnormal urine lab data with clinically significant	Day 36
Hematology assessments at Stage 2	any abnormal hematologic lab data with clinical significance	Day 29
Clinical chemistry assessments at Stage 2	any abnormal chemical lab data with clinical significanc	Day 29
Urinalysis assessments at Stage 2	any abnormal urine lab data with clinically significant	Day 29
Hematology assessments at Stage 3	any abnormal hematologic lab data with clinical significance	Day 29
Clinical chemistry assessments at Stage 3	any abnormal chemical lab data with clinical significanc	Day 29
Urinalysis assessments at Stage 3	any abnormal urine lab data with clinically significant	Day 29
Hematology assessments at Stage 4	any abnormal hematologic lab data with clinical significance	28 days after the end of cycle 4 treatment (each cycle is 7 days)
Clinical chemistry assessments at Stage 4	any abnormal chemical lab data with clinical significanc	28 days after the end of cycle 4 treatment (each cycle is 7 days)
Urinalysis assessments at Stage 4	any abnormal urine lab data with clinically significant	28 days after the end of cycle 4 treatment (each cycle is 7 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change between baseline and end of treatment in target area score (TAS) at Stage 1	Change between baseline and end of treatment in TAS that evaluates the target lesion's erythema (0-4), plaque elevation (0-4) and scaling (0-4) on a five-point scale for each item (higher scores mean a worse outcome)	Stage 1: Up to Day 36
Change between baseline and end of TAS at Stage 2	Change between baseline and end of treatment in TAS that evaluates the target lesion's erythema (0-4), plaque elevation (0-4) and scaling (0-4) on a five-point scale for each item	Up to Day 29
Change between baseline and end of TAS at Stage 3	Change between baseline and end of treatment in TAS that evaluates the target lesion's erythema (0-4), plaque elevation (0-4) and scaling (0-4) on a five-point scale for each item	Up to Day 6
Change between baseline and end of TAS at Stage 4	Change between baseline and end of treatment in TAS that evaluates the target lesion's erythema (0-4), plaque elevation (0-4) and scaling (0-4) on a five-point scale for each item	Up to the end of cycle 4 treatment (each cycle is 7 days)
TAS 50 at Stage 1	≧50% reduction in TAS score from baseline at the end of treatment	Up to Day 36
TAS 50 at Stage 2	≧50% reduction in TAS score from baseline at the end of treatment	Up to Day 29
TAS 50 at Stage 3	≧50% reduction in TAS score from baseline at the end of treatment	Up to Day 6
TAS 50 at Stage 4	≧50% reduction in TAS score from baseline at the end of treatment	Up to the end of cycle 4 treatment (each cycle is 7 days)
Physician global assessment (PGA) score of the target lesion at the end of treatment of Stage 1	Achieving a score of "clear" (grade 0) or "almost clear" (grade 1) and at least 2 grade improvement from the baseline score in a 7-point score (0-6, higher scores mean a worse outcome).	Up to Day 36
PGA score of the target lesion at the end of treatment of Stage 2	Achieving a score of "clear" (grade 0) or "almost clear" (grade 1) and at least 2 grade improvement from the baseline score in a 7-point score	Up to Day 29
PGA score of the target lesion at the end of treatment of Stage 3	Achieving a score of "clear" (grade 0) or "almost clear" (grade 1) and at least 2 grade improvement from the baseline score in a 7-point score	Up to Day 6
PGA score of the target lesion at the end of treatment of Stage 4	Achieving a score of "clear" (grade 0) or "almost clear" (grade 1) and at least 2 grade improvement from the baseline score in a 7-point score	Up to the end of cycle 4 treatment (each cycle is 7 days)
Disease relapse at Stage 2	Relapse is the loss of more than 50% of TAS improvement from baseline in patients who achieve a clinically meaningful response. Clinical meaningful response is defined as a reduction of ≥50% in TAS from baseline during the treatment.	Day 43
Disease relapse at Stage 3	Relapse is the loss of more than 50% of TAS improvement from baseline in patients who achieve a clinically meaningful response. Clinical meaningful response is defined as a reduction of ≥50% in TAS from baseline during the treatment.	Day 15 and Day 29
Disease relapse at Stage 4	Relapse is the loss of more than 50% of TAS improvement from baseline in patients who achieve a clinically meaningful response. Clinical meaningful response is defined as a reduction of ≥50% in TAS from baseline during the treatment.	14 days after cycle 4 treatment and 28 days after cycle 4 treatment (each cycle is 7 days)
Plasma KX01 concentrations (ng/ml) at Stage 1	Detection of plasma KX01 concentrations (ng/ml)	Up to Day 36
Plasma KX01 concentrations (ng/ml) at Stage 2	Detection of plasma KX01 concentrations (ng/ml)	Up to Day 29
Plasma KX01 concentrations (ng/ml) at Stage 3	Detection of plasma KX01 concentrations (ng/ml)	Up to Day 15
Plasma KX01 concentrations (ng/ml) at Stage 4	Detection of plasma KX01 concentrations (ng/ml)	14 days after cycle 4 treatment (each cycle is 7 days)

Collaborators and Investigators

• Sponsor: PharmaEssentia
• Collaborators: Athenex, Inc.
• Investigators: Principal Investigator: Jin-Bon Hong, M.D., Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan; Principal Investigator: Po-Yuan Wu, M.D., Ph.D., Department of Dermatology, China Medical University Hospital, Taichung, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2015
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): March 10, 2021

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: August 29, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 28, 2025
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Psoriasis; Phase I; Clinical trial; Ointment; KX01
• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Skin Diseases; Psoriasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tirbanibulin
• Other Study ID Numbers: B14-201

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No