Psoriasis
Conditions
Keywords
KX01, Ointment, Psoriasis, Phase I, Clinical trial
Brief summary
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
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.
Interventions
DRUGKX01 0.01% (0.1 mg/g)
Stage 1: 6 patients (KX01 0.01% \[0.1 mg/g\])
DRUGPlacebo
Contains same excipients with KX01 but do not contain Tirbanibulin
DRUGKX01 0.1% (1.0 mg/g)
Stage 2: 6 patients (KX01 0.1% \[1.0 mg/g\])
DRUGKX01 1% (10 mg/g) for 5 days
Stage 3: 6 patients (KX01 1% \[10 mg/g\]) for 5 days
DRUGKX01 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
Sponsors
PharmaEssentia
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinalysis assessments at Stage 4 | 28 days after the end of cycle 4 treatment (each cycle is 7 days) | any abnormal urine lab data with clinically significant |
| Vital signs at Stage 1 | Day 50 | any abnormal vital sign with clinical significance |
| Vital signs at Stage 2 | Day 43 | any abnormal vital sign with clinical significance |
| Vital signs at Stage 3 | Day 29 | any abnormal vital sign with clinical significance |
| Vital signs at Stage 4 | 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 1 | Day 36 | any abnormal finding of 12-lead ECG with clinical significance |
| 12-lead ECG at Stage 2 | Day 29 | any abnormal finding of 12-lead ECG with clinical significance |
| 12-lead ECG at Stage 3 | Day 29 | any abnormal finding of 12-lead ECG with clinical significance |
| 12-lead ECG at Stage 4 | 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 1 | Day 36 | any abnormal hematologic lab data with clinical significance |
| Clinical chemistry assessments at Stage 1 | Day 36 | any abnormal chemical lab data with clinical significance |
| Urinalysis assessments at Stage 1 | Day 36 | any abnormal urine lab data with clinically significant |
| Hematology assessments at Stage 2 | Day 29 | any abnormal hematologic lab data with clinical significance |
| Clinical chemistry assessments at Stage 2 | Day 29 | any abnormal chemical lab data with clinical significanc |
| Urinalysis assessments at Stage 2 | Day 29 | any abnormal urine lab data with clinically significant |
| Hematology assessments at Stage 3 | Day 29 | any abnormal hematologic lab data with clinical significance |
| Clinical chemistry assessments at Stage 3 | Day 29 | any abnormal chemical lab data with clinical significanc |
| Urinalysis assessments at Stage 3 | Day 29 | any abnormal urine lab data with clinically significant |
| Hematology assessments at Stage 4 | 28 days after the end of cycle 4 treatment (each cycle is 7 days) | any abnormal hematologic lab data with clinical significance |
| Clinical chemistry assessments at Stage 4 | 28 days after the end of cycle 4 treatment (each cycle is 7 days) | any abnormal chemical lab data with clinical significanc |
| Adverse event at Stage 1 | Day 50 | Incidence of adverse event |
| Adverse event at Stage 2 | Day 43 | Incidence of adverse event |
| Adverse event at Stage 3 | Day 29 | Incidence of adverse event |
| Adverse event at Stage 4 | 28 days after the end of cycle 4 treatment (each cycle is 7 days) | Incidence of adverse event |
| Local tolerability score at Stage 1 | Day 50 | 4-point (0-3) rating scale; higher scores mean a worse outcome |
| Local tolerability score at Stage 2 | Day 43 | 4-point (0-3) rating scale; higher scores mean a worse outcome |
| Local tolerability score at Stage 3 | Day 29 | 4-point (0-3) rating scale; higher scores mean a worse outcome |
| Local tolerability score at Stage 4 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease relapse at Stage 4 | 14 days after cycle 4 treatment and 28 days after cycle 4 treatment (each cycle is 7 days) | 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. |
| 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 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) |
| Change between baseline and end of TAS at Stage 2 | Up to Day 29 | 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 |
| Change between baseline and end of TAS at Stage 3 | Up to Day 6 | 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 |
| Change between baseline and end of TAS at Stage 4 | Up to the end of cycle 4 treatment (each cycle is 7 days) | 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 |
| TAS 50 at Stage 1 | Up to Day 36 | ≧50% reduction in TAS score from baseline at the end of treatment |
| TAS 50 at Stage 2 | Up to Day 29 | ≧50% reduction in TAS score from baseline at the end of treatment |
| TAS 50 at Stage 3 | Up to Day 6 | ≧50% reduction in TAS score from baseline at the end of treatment |
| TAS 50 at Stage 4 | Up to the end of cycle 4 treatment (each cycle is 7 days) | ≧50% reduction in TAS score from baseline at the end of treatment |
| Physician global assessment (PGA) score of the target lesion at the end of treatment of Stage 1 | Up to Day 36 | 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). |
| PGA score of the target lesion at the end of treatment of Stage 2 | Up to Day 29 | 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 |
| PGA score of the target lesion at the end of treatment of Stage 3 | Up to Day 6 | 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 |
| 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) | 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 |
| Disease relapse at Stage 2 | Day 43 | 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. |
| Disease relapse at Stage 3 | Day 15 and Day 29 | 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. |
| Plasma KX01 concentrations (ng/ml) at Stage 1 | Up to Day 36 | Detection of plasma KX01 concentrations (ng/ml) |
| Plasma KX01 concentrations (ng/ml) at Stage 2 | Up to Day 29 | Detection of plasma KX01 concentrations (ng/ml) |
| Plasma KX01 concentrations (ng/ml) at Stage 4 | 14 days after cycle 4 treatment (each cycle is 7 days) | Detection of plasma KX01 concentrations (ng/ml) |
| Plasma KX01 concentrations (ng/ml) at Stage 3 | Up to Day 15 | Detection of plasma KX01 concentrations (ng/ml) |
Outcome results
None listed