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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
28
Stage 1: 6 patients (KX01 0.01% \[0.1 mg/g\])
Contains same excipients with KX01 but do not contain Tirbanibulin
Stage 2: 6 patients (KX01 0.1% \[1.0 mg/g\])
Adverse event at Stage 1
Incidence of adverse event
Time frame: Day 50
Adverse event at Stage 2
Incidence of adverse event
Time frame: Day 43
Adverse event at Stage 3
Incidence of adverse event
Time frame: Day 29
Adverse event at Stage 4
Incidence of adverse event
Time frame: 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
Time frame: Day 50
Local tolerability score at Stage 2
4-point (0-3) rating scale; higher scores mean a worse outcome
Time frame: Day 43
Local tolerability score at Stage 3
4-point (0-3) rating scale; higher scores mean a worse outcome
Time frame: Day 29
Local tolerability score at Stage 4
4-point (0-3) rating scale; higher scores mean a worse outcome
Time frame: 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
Time frame: Day 50
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Stage 3: 6 patients (KX01 1% \[10 mg/g\]) for 5 days
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
Vital signs at Stage 2
any abnormal vital sign with clinical significance
Time frame: Day 43
Vital signs at Stage 3
any abnormal vital sign with clinical significance
Time frame: Day 29
Vital signs at Stage 4
any abnormal vital sign with clinical significance
Time frame: 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
Time frame: Day 36
12-lead ECG at Stage 2
any abnormal finding of 12-lead ECG with clinical significance
Time frame: Day 29
12-lead ECG at Stage 3
any abnormal finding of 12-lead ECG with clinical significance
Time frame: Day 29
12-lead ECG at Stage 4
any abnormal finding of 12-lead ECG with clinical significance
Time frame: 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
Time frame: Day 36
Clinical chemistry assessments at Stage 1
any abnormal chemical lab data with clinical significance
Time frame: Day 36
Urinalysis assessments at Stage 1
any abnormal urine lab data with clinically significant
Time frame: Day 36
Hematology assessments at Stage 2
any abnormal hematologic lab data with clinical significance
Time frame: Day 29
Clinical chemistry assessments at Stage 2
any abnormal chemical lab data with clinical significanc
Time frame: Day 29
Urinalysis assessments at Stage 2
any abnormal urine lab data with clinically significant
Time frame: Day 29
Hematology assessments at Stage 3
any abnormal hematologic lab data with clinical significance
Time frame: Day 29
Clinical chemistry assessments at Stage 3
any abnormal chemical lab data with clinical significanc
Time frame: Day 29
Urinalysis assessments at Stage 3
any abnormal urine lab data with clinically significant
Time frame: Day 29
Hematology assessments at Stage 4
any abnormal hematologic lab data with clinical significance
Time frame: 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
Time frame: 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
Time frame: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to Day 36
TAS 50 at Stage 2
≧50% reduction in TAS score from baseline at the end of treatment
Time frame: Up to Day 29
TAS 50 at Stage 3
≧50% reduction in TAS score from baseline at the end of treatment
Time frame: Up to Day 6
TAS 50 at Stage 4
≧50% reduction in TAS score from baseline at the end of treatment
Time frame: 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).
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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)
Time frame: Up to Day 36
Plasma KX01 concentrations (ng/ml) at Stage 2
Detection of plasma KX01 concentrations (ng/ml)
Time frame: Up to Day 29
Plasma KX01 concentrations (ng/ml) at Stage 3
Detection of plasma KX01 concentrations (ng/ml)
Time frame: Up to Day 15
Plasma KX01 concentrations (ng/ml) at Stage 4
Detection of plasma KX01 concentrations (ng/ml)
Time frame: 14 days after cycle 4 treatment (each cycle is 7 days)