Study to Evaluate Apo805K1 in Subjects With Moderate to Severe Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of 12 weeks of treatment with Apo805K1 in subjects with moderate to severe chronic plaque psoriasis.

Detailed Description
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A) To evaluate the safety and tolerability of 12 weeks of treatment with Apo805K1 B) To evaluate the pharmacokinetics of Apo805K1 following daily administration for 14 days C) To evaluate the efficacy and pharmacodynamics of Apo805K1

Official Title
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A 12-week Randomized, Double-blind, Placebo-controlled, Multicenter, Multiple Sequential Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Apo805K1 in Subjects With Moderate to Severe Chronic Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Apo805K1


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: A clinical diagnosis of moderate to severe chronic plaque psoriasis for at least 6 months (before Baseline assessment) with current body surface area (BSA) involvement ≥10% and Psoriasis Area Severity Index (PASI) ≥10. Male and female subjects 18 to 65 years of age, inclusive. At least one psoriatic plaque ≥6 mm in diameter (in a location suitable for biopsy). Signed and witnessed written informed consent form obtained prior to the first study intervention, as well as the ability to adhere to study restrictions, appointments and evaluation schedule. Main Exclusion Criteria: Treatment of psoriasis with biologic agents within 90 days prior to Baseline assessment and during the study. Treatment with methotrexate, cyclosporine, retinoids, hydroxyurea or other systemic agents within 30 days prior to Baseline assessment and during the study. Phototherapy within 30 days prior to Baseline assessment and during the study. Psoriasis topical therapy within 14 days prior to Baseline assessment and during the study (exception: non-medicated emollients and tar shampoo will be allowed). History of liver disease or abnormal liver enzymes Serum creatinine ≥1.5 times the upper limit of normal for age and sex-matched controls. Previous treatment with Apo805K1or Thymodepressin or other immunosuppressant drugs. Evidence of skin conditions other than psoriasis (e.g., eczema) that could interfere with psoriasis assessments. History of chronic infection or malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg Apo805K1, or placebo<br> | Drug: Apo805K1<br>* Sequential parallel dose escalation.<br>|
| Experimental: 30 mg Apo805K1, or placebo<br> | Drug: Apo805K1<br>* Sequential parallel dose escalation.<br>|
| Experimental: 60 mg Apo805K1, or placebo<br> | Drug: Apo805K1<br>* Sequential parallel dose escalation.<br>|
| Experimental: 100 mg Apo805K1, or placebo<br> | Drug: Apo805K1<br>* Sequential parallel dose escalation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events | The number of patients in each treatment group who reported at least 1 adverse event, including clinically significant changes from baseline in vital signs, 12-lead ECG, physical examinations and laboratory tests, from the time of the first dose until the last study visit. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | Cmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. . | 12 hours | 
| Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | Tmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. | 12 hours | 
| AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14 | AUC 0-infinity for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. | 12 hours | 
| T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14 | T 1/2 for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. | 12 hours | 
| Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores | PASI is a quantitative measure of psoriasis that combines an assessment of the severity of lesions and a measurement of how much of the body surface area is affected into a single score ranging from 0 (no disease) to 72 (maximal disease). Thus, a decrease in PASI score indicates improvement. This outcome measure compared the difference in change in PASI score from baseline to Week 12 between the active treatment groups and the placebo group. | Baseline to 12 Weeks | 
| Efficacy of APO805K1 as Assessed by Achievement of PASI-75 | The proportion of patients in each treatment group who achieved at least a 75% improvement in PASI score from baseline at Week 12 | 12 weeks | 
| Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores | The LS-PGA is a standardized method for determining categories of psoriasis severity. The percentage of body surface area involved is assessed on a scale ranging from 1 (0%) to 7 (51-100%); measures of plaque severity (thickness, erythema, and scaling) are assessed using a 4-point scale ranging from none to marked; and an algorithm is used to combine the above scores to determine a final score on a scale ranging from 0 (clear) to 7 (very severe). Thus, a decrease in LS-PGA score indicates improvement. This outcome measure compared the difference in change in LS-PGA score from baseline to Week 12 between the active treatment groups and the placebo group. | Baseline to 12 weeks | 
| Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score | In the PGA, the physician assigns a single estimate of a patient's overall severity of the disease using a scale ranging from 0 (Clear) to 7 (Severe). (Unlike the LS-PGA, the individual elements of psoriasis plaque morphology or degree of body surface area involvement are not quantified.) Thus, a decrease in PGA score indicates improvement. This outcome measure compared the difference in change in PGA score from baseline to Week 12 between the active treatment groups and the placebo group. | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild to Moderate Chronic Plaque Psoriasis