A Study 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 Phase Ib clinical study of multiple dose escalation of AK111 in subjects with moderate-to-severe plaque psoriasis

Detailed Description
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This is a randomized, double-blind, placebo-controlled phase Ib clinical study. This study aims to determine the safety, tolerance, pharmacokinetics(PK) and Pharmacodynamics (PD) characteristics, immunogenicity and preliminary clinical efficacy of multiple dose escalation administration of AK111 in subjects with moderate-to-severe plaque psoriasis..

Official Title
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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AK111 in Subjects With Moderate-to-severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: AK111
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe plaque-type psoriasis diagnosed for at least 6 months; Subjects with moderate-to-severe plaque psoriasis at baseline, who were defined as follows: Body Surface Area (BSA) ≥ 10%, PASI ≥ 12 and SPGA score ≥ 3; Subjects with a history of systemic therapy or phototherapy for psoriasis at least once before, or suitable to receive systemic therapy or phototherapy for psoriasis assessed by investigator; Women of childbearing age is not pregnant or lactating, and the subjects and their partners voluntarily take contraceptive measures considered effective by the investigator during the treatment period and at least 6 months after the last receipt of the study drug. Exclusion Criteria: Forms of psoriasis other than chronic plaque-type psoriasis; History or evidence of active/latent tuberculosis; Positive results of confirmatory serology test for hepatitis B, hepatitis C,HIV or syphilis at screening; History of serious infection within 2 months before screening; History of malignancy of any organ system; Inadequate washout period for prior psoriatic 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, 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: 60 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<br> | Drug: AK111<br>* Subjects will receive one of four escalated doses of AK111 (75mg/150mg/300mg/450mg) injection subcutaneously.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subjects will receive corresponding dose of placebo injection subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Safety | Incidence of treatment emergent adverse events (TEAE), serious adverse events (SAE). | Baseline till Week 20 | 
| PK evaluation: T1/2 | Assessment of elimination half-life (T1/2) after AK111 administration. | Baseline till week 20 | 
| PK evaluation: AUC | Assessment of area under curve (AUC) after AK111 administration. | Baseline till week 20 | 
| PK evaluation: Cmax | Assessment of maximum plasma concentration (Cmax) after AK111 administration. | Baseline till week 20 | 
| PK evaluation: Tmax | Assessment of time to maximum plasma concentration (Tmax) after AK111 administration. | Baseline till week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI 75 | Proportion of subjects who achieve Psoriasis Area and Severity Index (PASI) 75 response which means whose PASI score decrease at least 75 percent compared with baseline at week 12. PASI is a measure of overall psoriasis severity and coverage. The PASI score is in the range of 0 (no psoriasis on the body) to 72 (the most severe case of psoriasis). | At week 12 | 
| PASI 90 | Proportion of subjects who achieve PASI 90 response which means whose PASI score decrease at least 90 percent compared with baseline at week 12. PASI is a measure of overall psoriasis severity and coverage. The PASI score is in the range of 0 (no psoriasis on the body) to 72 (the most severe case of psoriasis). | At week 12 | 
| PASI 100 | Proportion of subjects who achieve PASI 100 response which means whose PASI score decrease 100 percent compared with baseline at week 12. PASI is a measure of overall psoriasis severity and coverage. The PASI score is in the range of 0 (no psoriasis on the body) to 72 (the most severe case of psoriasis). | At week 12 | 
| sPGA 0/1 | Proportion of subjects who achieve Static Physicians Global Assessment (sPGA) 0/1 which means whose sPGA score is clear or almost-clear at week 12. The sPGA is a measure of global assessment of the patient's overall severity, which could be converted to numerals ranging from 0 to 5 (clear = 0, almost-clear = 1, mild = 2, moderate = 3, marked = 4, and severe = 5). | At week 12 | 
| Immunogenicity | Proportion of subjects with detectable anti-drug antibody (ADA). | Baseline till week 20 |