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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 主要终点
- Adverse event at Stage 2
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomization and masking will be conducted in stage 1 and stage 2. Eight patients are randomized to received KX01 or placebo control in a ratio of 3:1 (KX01 versus placebo) in these 2 stages. Double blind are applied to the assignment of KX01 and placebo.
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •Not of childbearing potential: Surgically sterilized, undergone a hysterectomy, amenorrhea for ≥ 12 months and considered post-menopausal;
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: KX01 0.01% (0.1 mg/g) (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: KX01 0.1% (1.0 mg/g) (Drug)
Placebo in stage 2
Two patients in the stage 2 will receive placebo treatment for 4 weeks, followed by 2-week follow-up.
干预措施: Placebo (Drug)
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.
干预措施: KX01 1% (10 mg/g) for 5 days (Drug)
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.
干预措施: KX01 1% (10 mg/g) for consecutive 5 days and 2 days rest for 1 cycle, and repeat up to 4 cycles (Drug)
结局指标
主要结局
Adverse event at Stage 2
时间窗: Day 43
Incidence of adverse event
Local tolerability score at Stage 3
时间窗: Day 29
4-point (0-3) rating scale; higher scores mean a worse outcome
Vital signs at Stage 1
时间窗: Day 50
any abnormal vital sign with clinical significance
Hematology assessments at Stage 1
时间窗: Day 36
any abnormal hematologic lab data with clinical significance
Vital signs at Stage 4
时间窗: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
any abnormal vital sign with clinical significance
12-lead ECG at Stage 2
时间窗: Day 29
any abnormal finding of 12-lead ECG with clinical significance
12-lead ECG at Stage 3
时间窗: Day 29
any abnormal finding of 12-lead ECG with clinical significance
Adverse event at Stage 4
时间窗: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
Incidence of adverse event
12-lead ECG at Stage 4
时间窗: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
any abnormal finding of 12-lead ECG with clinical significance
Hematology assessments at Stage 3
时间窗: Day 29
any abnormal hematologic lab data with clinical significance
Clinical chemistry assessments at Stage 3
时间窗: Day 29
any abnormal chemical lab data with clinical significanc
Adverse event at Stage 1
时间窗: Day 50
Incidence of adverse event
Local tolerability score at Stage 1
时间窗: Day 50
4-point (0-3) rating scale; higher scores mean a worse outcome
Local tolerability score at Stage 2
时间窗: Day 43
4-point (0-3) rating scale; higher scores mean a worse outcome
12-lead ECG at Stage 1
时间窗: Day 36
any abnormal finding of 12-lead ECG with clinical significance
Hematology assessments at Stage 4
时间窗: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
any abnormal hematologic lab data with clinical significance
Adverse event at Stage 3
时间窗: Day 29
Incidence of adverse event
Local tolerability score at Stage 4
时间窗: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
4-point (0-3) rating scale; higher scores mean a worse outcome
Vital signs at Stage 2
时间窗: Day 43
any abnormal vital sign with clinical significance
Vital signs at Stage 3
时间窗: Day 29
any abnormal vital sign with clinical significance
Urinalysis assessments at Stage 1
时间窗: Day 36
any abnormal urine lab data with clinically significant
Clinical chemistry assessments at Stage 2
时间窗: Day 29
any abnormal chemical lab data with clinical significanc
Urinalysis assessments at Stage 2
时间窗: Day 29
any abnormal urine lab data with clinically significant
Clinical chemistry assessments at Stage 1
时间窗: Day 36
any abnormal chemical lab data with clinical significance
Urinalysis assessments at Stage 4
时间窗: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
any abnormal urine lab data with clinically significant
Hematology assessments at Stage 2
时间窗: Day 29
any abnormal hematologic lab data with clinical significance
Urinalysis assessments at Stage 3
时间窗: Day 29
any abnormal urine lab data with clinically significant
Clinical chemistry assessments at Stage 4
时间窗: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
any abnormal chemical lab data with clinical significanc
次要结局
- Change between baseline and end of treatment in target area score (TAS) at Stage 1(Stage 1: Up to Day 36)
- Change between baseline and end of TAS at Stage 2(Up to Day 29)
- Change between baseline and end of TAS at Stage 4(Up to the end of cycle 4 treatment (each cycle is 7 days))
- TAS 50 at Stage 1(Up to Day 36)
- TAS 50 at Stage 3(Up to Day 6)
- Physician global assessment (PGA) score of the target lesion at the end of treatment of Stage 1(Up to Day 36)
- PGA score of the target lesion at the end of treatment of Stage 2(Up to Day 29)
- PGA score of the target lesion at the end of treatment of Stage 3(Up to Day 6)
- PGA score of the target lesion at the end of treatment of Stage 4(Up to the end of cycle 4 treatment (each cycle is 7 days))
- Disease relapse at Stage 2(Day 43)
- Disease relapse at Stage 3(Day 15 and Day 29)
- Change between baseline and end of TAS at Stage 3(Up to Day 6)
- TAS 50 at Stage 2(Up to Day 29)
- TAS 50 at Stage 4(Up to the end of cycle 4 treatment (each cycle is 7 days))
- Plasma KX01 concentrations (ng/ml) at Stage 2(Up to Day 29)
- Plasma KX01 concentrations (ng/ml) at Stage 4(14 days after cycle 4 treatment (each cycle is 7 days))
- Disease relapse at Stage 4(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(Up to Day 36)
- Plasma KX01 concentrations (ng/ml) at Stage 3(Up to Day 15)