A Study of PRCL-02 in Moderate to Severe Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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The aim of this study is to evaluate safety, tolerability, and efficacy of PRCL-02 in moderate to severe chronic plaque psoriasis

Official Title
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A Phase 2a Study to Evaluate Safety, Tolerability, and Efficacy of PRCL-02 in Patients With Moderate to Severe Chronic Plaque Psoriasis

Conditions
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Psoriasis Vulgaris, Plaque Psoriasis

Intervention / Treatment
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* Drug: PRCL-02
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presents with moderate to severe psoriasis vulgaris based on: Chronic psoriasis vulgaris for at least 6 months Plaque psoriasis involving at least 10% body surface area (BSA) Psoriasis Area and Severity Index (PASI) total score of at least 12 Have at least 2 evaluable plaques located in 2 different body regions. (Also for participants who elect to have plaques biopsied, should be suitable for a total of 4 punch biopsies each, and one lesion, preferably on a region of the body that is not normally exposed (e.g., trunk), should be selected for biopsy) Have a Static Physician's Global Assessment (sPGA) score of greater than or equal to (≥)3 Are candidates for systemic therapy Have a body mass index (BMI) within the range of 18 to 40 kilograms per square meter (kg/m2) Women who are of childbearing potential must agree to use 1 highly effective method of contraception, or a combination of 2 effective methods of contraception for the entirety of the study Women of non childbearing potential are defined as women who are: Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis; or Post-menopausal, defined as either: A woman at least 50 years of age with an intact uterus, not on hormone therapy, who has had either: cessation of menses for at least 1 year; or at least 6 months of spontaneous amenorrhea with a follicle stimulating hormone greater than (>)40 milli-international units per milliliter (mIU/mL); or A woman 55 years or older not on hormone therapy, who has had at least 6 months of spontaneous amenorrhea; or A woman at least 55 years of age with a diagnosis of menopause prior to staring hormone replacement therapy Exclusion Criteria: Currently enrolled in any other clinical trial involving a study drug or device, or any other type of medical research judged not compatible with this study (Participants in the previous PRCL study (SMAD) will be allowed to be included in this study, provided that they meet all inclusion and none of the exclusion criteria) Participated in a clinical study within last 30 days Present with pustular, erythrodermic psoriasis, generalized pustular psoriasis, or acute guttate psoriasis Have current serious or unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including a history of ischemic or structural heart disease, conduction system disease or history of clinically significant arrhythmia), endocrinologic, neurologic, psychiatric, immunologic, hematologic, or dermatologic disease Have a history of clinically significant severe drug allergies or severe post treatment hypersensitivity reactions Have received inactivated vaccine within 4 weeks prior to dosing in this study, or a live vaccine within the last 3 months A history of clinically significant opportunistic infection (for example, invasive candidiasis or Pneumocystis pneumonia) Had symptomatic herpes zoster within last 3 months or other recent or ongoing infection Present with any of the following laboratory test results: Positive QuantiFERON®-tuberculosis test For women, positive serum pregnancy test Evidence of Human Immunodeficiency Virus (HIV) infection or are positive for HIV antibodies Positive test for active hepatitis B Positive of anti-hepatitis C antibody with confirmed presence of hepatitis C virus, or chronic liver disease Evidence of clinically significant hepatic or renal impairment Clinically significant ECG (electrocardiogram) abnormalities or personal or family history of heart disease, including: Confirmed corrected QT interval with Frederica's correction (QTcF) >450 milliseconds (msec) for both men and women Specific bundle branch blocks, irregular rhythms, history of unexplained syncope, or family history of unexplained death Are receiving any of the following therapies for psoriasis: Systemic retinoids within last 12 weeks Systemic psoriasis therapy, such as psoralen and ultraviolet A (PUVA) light therapy, cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, azathioprine, or phototherapy (including ultraviolet B or self-treatment with tanning beds or therapeutic sunbathing) within last 4 weeks Topical psoriasis treatment within last 2 weeks; or Any biologic agent within the following washout periods: 30 days for anti-tumor necrosis factor (TNF) inhibitors, and 90 days for other agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRCL-02 Dose 1<br>Loading dose followed by a once daily maintenance dose commencing on Day 2 and continuing for 12 weeks | Drug: PRCL-02<br>* Oral tablets<br>|
| Experimental: PRCL-02 Dose 2<br>Loading dose followed by a once daily maintenance dose commencing on Day 2 and continuing for 12 weeks | Drug: PRCL-02<br>* Oral tablets<br>|
| Placebo Comparator: Placebo<br>Loading dose followed by a once daily maintenance dose at matching treatment levels, commencing on Day 2 and continuing for 12 weeks | Drug: Placebo<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement | Following 12 weeks of treatment. The Psoriasis Area and Severity Index (PASI) scores the severity of disease on a scale from 0 to 72 (where a score of 72 indicates extreme disease severity). PASI 75 indicates 75% improvement from baseline to Week 12 in the Psoriasis Area and Severity Index | Baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Treatment Emergent Adverse Event | Following 12 weeks of treatment | Baseline up to week 18 | 
| Area Under the Concentration Time Curve (AUC0-τ) | Steady state after 12 weeks of treatment | Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84 | 
| Maximum Observed Drug Concentration (Cmax) | Steady state after 12 weeks of treatment | Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84 | 
| Time to Reach Maximum Observed Drug Concentration (Tmax) | Steady state after 12 weeks of treatment | Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84 |