A Phase 2 Study of Efficacy and Safety of AK111 in Subjects With Moderate-to-Severe Psoriasis

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multi-center Phase II clinical study to evaluate the efficacy and safety of AK111 for the treatment of moderate to severe plaque psoriasis.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multi-center Phase II clinical study to evaluate the efficacy and safety of AK111 in subjects with moderate to severe plaque psoriasis. The study will consist of 4 periods: up to 4 weeks screening period, 12 weeks placebo-controlled period,12 weeks crossover treatment period,44 weeks long-term treatment period.

Official Title
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A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of AK111 in Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: AK111/Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female, 18 to 75 years of age Moderate to severe plaque-type psoriasis diagnosed for at least 6 months Moderate-to-severe plaque psoriasis as defined at baseline by meeting all three criteria: Clinical diagnosis of stable plaque psoriasis with involvement of ≥ 10% body surface area. Psoriasis area and severity index(PASI) ≥12. Static Physicians Global Assessment score ≥3. Subjects with a history of an inadequate response, intolerable or medically inappropriate use of systemic therapy and/or phototherapy. Subjects who are women of childbearing potential must have a negative urine pregnancy test at screening and must be practicing an adequate, medically acceptable method of birth control for at least 8 months after the last study drug administration. Key Exclusion Criteria: Forms of psoriasis other than chronic plaque-type psoriasis. History or evidence of active TB, Patients with evidence of latent tuberculosis may enter the trial after sufficient treatment according to protocol. Positive results of confirmatory serology test for hepatitis B, hepatitis C, HIV or syphilis at screening. History of a serious or systemic infection within 2 months before screening. History of malignancy of any organ system within the past 5 years. Inadequate washout period for prior drug therapy. Previous use of secukinumab, ixekizumab or any other drug that targets IL-17 or IL-17 receptor. Any medical conditions, in the opinion of the Investigator or the Sponsor's medical monitor, would place the subject at risk, interfere with study participation or study results interpretation.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK111 Regimen 1<br>AK111 Regimen 1 - subcutaneous injection every 4 weeks up to 60 weeks | Biological: AK111/Placebo<br>* After loading dose, investigational drug was administered subcutaneously up to 60 weeks.<br>|
| Experimental: AK111 Regimen 2<br>AK111 Regimen 2 - subcutaneous injection every 4 weeks up to 60 weeks | Biological: AK111/Placebo<br>* After loading dose, investigational drug was administered subcutaneously up to 60 weeks.<br>|
| Experimental: AK111 Regimen 3<br>AK111 Regimen 3 - subcutaneous injection every 4 weeks up to 60 weeks | Biological: AK111/Placebo<br>* After loading dose, investigational drug was administered subcutaneously up to 60 weeks.<br>|
| Experimental: AK111 Regimen 4<br>AK111 Regimen 4 - subcutaneous injection every 4 weeks up to 60 weeks | Biological: AK111/Placebo<br>* After loading dose, investigational drug was administered subcutaneously up to 60 weeks.<br>|
| Placebo Comparator: Placebo to AK111<br>Placebo to AK111-Placebo subcutaneous injection, then 1:1 randomized to AK111 Regimen 3 or Regimen 4 at week 12 | Biological: AK111/Placebo<br>* After loading dose, investigational drug was administered subcutaneously up to 60 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve Psoriasis Area and Severity Index (PASI) 90 response or higher at week 12 |  | At week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve PASI 75 response or higher at week 12 |  | At week 12 | 
| Proportion of subjects who achieve static Physician Global Assessment (sPGA) 0 or 1 at week 12 |  | At week 12 | 
| Proportion of subjects who achieve PASI 50, PASI 75, PASI 90 and PASI 100 response up to 68 weeks |  | Baseline to week 68 | 
| AK111 concentrations in serum at different time points |  | Baseline to week 68 | 
| Number and proportion of subjects who developed anti-drug antibodies (ADAs) |  | Baseline to week 68 | 
| Change in serum IL-17A level (Pharmacodynamics parameter） |  | Baseline to week 68 | 
| Adverse events (AEs)/serious adverse events (SAEs) |  | Baseline to week 68 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AK111, efficacy, safety