A Study to Evaluate the Efficacy and Safety of AK111 in Subjects With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter phase III clinical study to evaluate the efficacy and safety of AK111 in the treatment of subjects with moderate to severe plaque psoriasis.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter phase III clinical study to evaluate the efficacy and safety of AK111 in the treatment of subjects with moderate to severe plaque psoriasis. Subjects will be randomized to receive AK111 or placebo subcutaneously and followed up to week 56.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Clinical Study to Evaluate the Efficacy and Safety of AK111 in the Treatment of Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Psoriasis, Skin Diseases

Intervention / Treatment
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* Drug: AK111
* Drug: AK111
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged ≥18 years old. Subjects diagnosed with moderate to severe plaque psoriasis with or without psoriatic arthritis. At screening and baseline, PASI score ≥ 12 , Body Surface Area(BSA) ≥ 10%, sPGA ≥ 3. Suitable for systematic therapy assessed by investigators. Subjects who are women of childbearing potential must have a negative pregnancy test at screening and must be practicing an adequate, medically acceptable method of birth control during the study and for at least 6 months after the last study drug administration. Exclusion Criteria: Types of psoriasis other than chronic plaque-type psoriasis. Drug-induced psoriasis. Evidence of active TB. Patients with evidence of latent tuberculosis may enter the trial after sufficient treatment had initiated and maintained according to protocol. Positive results of confirmatory test for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or syphilis. History of repeated chronic infection, had any serious infection or systemic infection within 2 months before screening. Progressive or uncontrolled symptoms or signs of circulatory, respiratory, digestive, neuropsychiatric or psychological, hematological, endocrine and other systems before randomization. History of malignant tumour within 5 years before screening. Previous or current autoimmune diseases. Allergic to any component of the investigational drug, or have had severe allergic reactions to monoclonal antibodies.

Ages Eligible for Study
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Minimum Age: 18 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: AK111 regimen 1<br> | Drug: AK111<br>* AK111 regimen 1- subcutaneous injection at week 0,1,2, 3,4 and every 4 weeks thereafter until week 48. The primary endpoint will be evaluated at week 12 and followed up to week 56.<br>|
| Experimental: AK111 regimen 2<br> | Drug: AK111<br>* AK111 regimen 2- subcutaneous injection at week 0,1,2, 3,4 and every 4 weeks thereafter until week 48. The primary endpoint will be evaluated at week 12 and followed up to week 56.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo- subcutaneous injection at week 0,1,2, 3, 4 and week 8. AK111 regimen 2-subcutaneous injection every 4 weeks from week 12 to week 48. The primary endpoint will be evaluated at week 12 and followed up to week 56.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects who achieved at least 75% reduction in psoriasis area and severity index(PASI) score from baseline (PASI 75) and the percentage of subjects who achieved static physician global assessment(sPGA) 0/1 at week 12. | PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%),and severity is estimated by clinical signs, erythema, induration and desquamation: scale 0 (none) to 4 (maximum).Final PASI = sum of severity parameters for each area * area score weight of section (head: 0.1, arms: 0.2, body: 0.3,legs: 0.4).PASI 50, PASI75 and PASI 90 were defined as participants achieving >= 50%, >= 75% or >= 90% improvement from baseline, respectively.The sPGA is an instrument providing a subjective evaluation of the overall severity of psoriasis, based on severity of induration, scaling, and erythema. The scores are: 0 = clear; 1 = minimal; 2 = mild; 3 = moderate; 4 = marked; 5 =severe. | at week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects who achieved at least 90% reduction in PASI score from baseline (PASI 90) at week 12. |  | at week 12 | 
| The percentage of subjects who achieved PASI 75 and the percentage of subjects who achieved sPGA 0/1 at week 52. |  | at week 52 |