Clinical trial NCT05522816: KX01 Ointment Phase 1 Study in Patients With Plaque Type Psoriasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: KX01
Ointment
Psoriasis
Phase I
Clinical trial
Lead sponsor: PharmaEssentia
Sponsor class: INDUSTRY
Collaborators: name: Athenex, Inc.
First posted: 2022-08-31
Enrollment: 28
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse event at Stage 1
timeFrame: Day 50
measure: Adverse event at Stage 2
timeFrame: Day 43
measure: Adverse event at Stage 3
timeFrame: Day 29
measure: Adverse event at Stage 4
timeFrame: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
measure: Local tolerability score at Stage 1
timeFrame: Day 50
measure: Local tolerability score at Stage 2
timeFrame: Day 43
measure: Local tolerability score at Stage 3
timeFrame: Day 29
measure: Local tolerability score at Stage 4
timeFrame: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
measure: Vital signs at Stage 1
timeFrame: Day 50
measure: Vital signs at Stage 2
timeFrame: Day 43
measure: Vital signs at Stage 3
timeFrame: Day 29
measure: Vital signs at Stage 4
timeFrame: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
measure: 12-lead ECG at Stage 1
timeFrame: Day 36
measure: 12-lead ECG at Stage 2
timeFrame: Day 29
measure: 12-lead ECG at Stage 3
timeFrame: Day 29
measure: 12-lead ECG at Stage 4
timeFrame: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
measure: Laboratory assessments at Stage 1
timeFrame: Day 36
measure: Laboratory assessments at Stage 2
timeFrame: Day 29
measure: Laboratory assessments at Stage 3
timeFrame: Day 29
measure: Laboratory assessments at Stage 4
timeFrame: 28 days after the end of cycle 4 treatment (each cycle is 7 days)
Secondary outcomes:
measure: Change between baseline and end of treatment in target area score (TAS) at Stage 1
timeFrame: Stage 1: Up to Day 36
measure: Change between baseline and end of TAS at Stage 2
timeFrame: Up to Day 29
measure: Change between baseline and end of TAS at Stage 3
timeFrame: Up to Day 6
measure: Change between baseline and end of TAS at Stage 4
timeFrame: Up to the end of cycle 4 treatment (each cycle is 7 days)
measure: TAS 50 at Stage 1
timeFrame: Up to Day 36
measure: TAS 50 at Stage 2
timeFrame: Up to Day 29
measure: TAS 50 at Stage 3
timeFrame: Up to Day 6
measure: TAS 50 at Stage 4
timeFrame: Up to the end of cycle 4 treatment (each cycle is 7 days)
measure: Physician global assessment (PGA) score of the target lesion at the end of treatment of Stage 1
timeFrame: Up to Day 36
measure: PGA score of the target lesion at the end of treatment of Stage 2
timeFrame: Up to Day 29
measure: PGA score of the target lesion at the end of treatment of Stage 3
timeFrame: Up to Day 6
measure: PGA score of the target lesion at the end of treatment of Stage 4
timeFrame: Up to the end of cycle 4 treatment (each cycle is 7 days)
measure: Disease relapse at Stage 2
timeFrame: Day 43
measure: Disease relapse at Stage 3
timeFrame: Day 15 and Day 29
measure: Disease relapse at Stage 4
timeFrame: 14 days after cycle 4 treatment and 28 days after cycle 4 treatment (each cycle is 7 days)
measure: Plasma KX01 concentrations (ng/ml) at Stage 1
timeFrame: Up to Day 36
measure: Plasma KX01 concentrations (ng/ml) at Stage 2
timeFrame: Up to Day 29
measure: Plasma KX01 concentrations (ng/ml) at Stage 3
timeFrame: Up to Day 15
measure: Plasma KX01 concentrations (ng/ml) at Stage 4
timeFrame: 14 days after cycle 4 treatment (each cycle is 7 days)
Other outcomes:
Locations:
Study officials:
affiliation: Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
name: Jin-Bon Hong, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Dermatology, China Medical University Hospital, Taichung, Taiwan
name: Po-Yuan Wu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: