KX01 Ointment Phase 1 Study in Patients With Plaque Type Psoriasis

Study Overview
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Brief Summary
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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.

Detailed Description
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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. 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.

Official Title
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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

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: KX01 0.01% (0.1 mg/g)
* Drug: Placebo
* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study will be sequentially performed in four stages, including stage 1 to stage 4. If no major safety concern was identified in the previous stage, as well as an unanimous consent by the sponsor and the principle investigator(s), the study will proceed to the next stage.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KX01 0.01% in stage I<br>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)<br>* Stage 1: 6 patients (KX01 0.01% [0.1 mg/g])<br>|
| Placebo Comparator: Placebo in stage 1<br>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<br> <br> |
| Experimental: KX01 0.1% in stage 2<br>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)<br>* Stage 2: 6 patients (KX01 0.1% [1.0 mg/g])<br>|
| Placebo Comparator: Placebo in stage 2<br>Two patients in the stage 2 will receive placebo treatment for 4 weeks, followed by 2-week follow-up. | Drug: Placebo<br> <br> |
| Experimental: KX01 1% for 5 days in stage 3<br>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<br>* Stage 3: 6 patients (KX01 1% [10 mg/g]) for 5 days<br>|
| Experimental: KX01 1% for consecutive 5 days and 2 days rest for 1 cycle, and repeat up to 4 cycles in stage 4<br>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<br>* 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<br>|

What is the study measuring?
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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 |  | Day 50 | 
| Vital signs at Stage 2 |  | Day 43 | 
| Vital signs at Stage 3 |  | Day 29 | 
| Vital signs at Stage 4 |  | 28 days after the end of cycle 4 treatment (each cycle is 7 days) | 
| 12-lead ECG at Stage 1 |  | Day 36 | 
| 12-lead ECG at Stage 2 |  | Day 29 | 
| 12-lead ECG at Stage 3 |  | Day 29 | 
| 12-lead ECG at Stage 4 |  | 28 days after the end of cycle 4 treatment (each cycle is 7 days) | 
| Laboratory assessments at Stage 1 | hematology, clinical chemistry and urinalysis | Day 36 | 
| Laboratory assessments at Stage 2 | hematology, clinical chemistry and urinalysis | Day 29 | 
| Laboratory assessments at Stage 3 | hematology, clinical chemistry and urinalysis | Day 29 | 
| Laboratory assessments at Stage 4 | hematology, clinical chemistry and urinalysis | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KX01, Ointment, Psoriasis, Phase I, Clinical trial