Clinical Study of AK101 in Subjects With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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This is a multiple-center, randomized, double-blind, placebo-controlled Phase IIb study to evaluate the efficacy and safety of AK101, an anti-IL-12/23 p40 antibody, when administered subcutaneously, in subjects with moderate-to-severe plaque psoriasis. The study will consist of 3 periods: up to 4 weeks screening, 12 weeks double-blinded treatment and long-term follow-up period(up to 52 weeks).

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Phase IIb Clinical Study of AK101 in Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Biological: AK101
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had Plaque Psoriasis diagnosed at least 6 months prior to screening. Clinical diagnosis of stable plaque psoriasis with involvement of ≥ 10% body surface area. Psoriasis area and severity index(PASI) ≥12. Physicians Global Assessment score ≥3. Candidate for systemic therapy, defined as having psoriasis inadequately controlled by topical treatment (including topical corticosteroids) and/or phototherapy and/or previous systemic therapy. Women of childbearing potential should not be in pregnancy or lactation, men and women of childbearing potential must agree to use adequate birth control measures during study participation and for 6 months after the last doses of study treatment. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol. Exclusion Criteria: Had nonplaque forms of psoriasis (e.g., Guttate, erythrodermic, or pustular). Had other active skin diseases or skin infections (e.g., Bacterial, fungal or viral infection) that could affect psoriasis evaluation. Had imaging diagnosis of pulmonary infection or fibrosis during the 3 months prior to screening. History or evidence of active or latent tuberculosis at screening. Serious systemic infections or local infections during the 2 months prior to screening. History of cancer, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved). Known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study. Known history of alcohol or drug abuse. History or known presence of recurrent or chronic infection (e.g., hepatitis or C, human immunodeficiency virus [HIV], syphilis, TB). Had received any DMARDs (e.g., Anti-malaria drug, retinoids, interferon, lithium) during 2 weeks prior to screening. Had received any physical therapy (e.g., PUVA, ultra-violet therapy, tanning beds) during 2 weeks prior to screening. Had received any systemic psoriasis therapy (e.g., Glucocorticoid, retinoids, ciclosporin, methotrexate, or tripterygium) during 4 weeks prior to screening. Had enrolled in any other trials during 3 months prior to screening or concurrently enrolled in any other trials. Had received previous treatment with any anti-IL-12/IL-23, IL-12, IL-23, IL-17 therapy for the treatment of psoriasis or psoriatic arthritis. Had received natalizumab or any other drugs that regulate B cells or T cells (rituximab, abatacept, alemtuzumab) during 12 months prior to screening. Had received other biologic therapy (e.g., TNF inhibitor) during 6 months prior to screening.

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: AK101 45mg every 8 weeks<br>AK101 45mg on Week 0 and 4 administered subcutaneously followed by AK101 45mg administered subcutaneously every 8 weeks | Biological: AK101<br>* an anti-IL-12/23p40 monoclonal antibody<br>|
| Experimental: AK101 45mg - every 12 weeks<br>AK101 45mg on Week 0 and 4 administered subcutaneously followed by AK101 45mg administered subcutaneously every 12 weeks | Biological: AK101<br>* an anti-IL-12/23p40 monoclonal antibody<br>|
| Experimental: AK101 90mg - every 8 weeks<br>AK101 90mg on Week 0 and 4 administered subcutaneously followed by AK101 90mg administered subcutaneously every 8 weeks | Biological: AK101<br>* an anti-IL-12/23p40 monoclonal antibody<br>|
| Experimental: AK101 90mg -every 12 weeks<br>AK101 90mg on Week 0 and 4 administered subcutaneously followed by AK101 90mg administered subcutaneously every 12 weeks | Biological: AK101<br>* an anti-IL-12/23p40 monoclonal antibody<br>|
| Experimental: AK101 135mg -every 8 weeks<br>AK101 135mg on Week 0 and 4 administered subcutaneously followed by AK101 135mg administered subcutaneously every 8 weeks | Biological: AK101<br>* an anti-IL-12/23p40 monoclonal antibody<br>|
| Experimental: AK101 135mg -every 12 weeks<br>AK101 135mg on Week 0 and 4 administered subcutaneously followed by AK101 135mg administered subcutaneously every 12 weeks | Biological: AK101<br>* an anti-IL-12/23p40 monoclonal antibody<br>|
| Placebo Comparator: Placebo to AK101<br>Placebo on Week 0 and 4 administered subcutaneously followed by AK101 135mg administered subcutaneously at Week 12, 16 and then every 12 weeks | Biological: AK101<br>* an anti-IL-12/23p40 monoclonal antibody<br>Biological: Placebo<br>* matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75) at Week 12 |  | Week 12 | 
| Incidence of treatment emergent adverse events (TEAEs) |  | From the time of signing the informed consent form till last follow-up visit (Up to Week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who achieved ≥ 90% reduction in Psoriasis Area and Severity Index (PASI90) at Week 12 |  | At baseline and Week 12 | 
| Number of participants who achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75) |  | Up to Week 52 (except for Week 12) | 
| Number of participants who achieved ≥ 90% reduction in Psoriasis Area and Severity Index (PASI90) |  | Up to Week 52( except for Week 12) | 
| Number of participants who achieved 100% reduction in Psoriasis Area and Severity Index (PASI100) at Week 12 |  | Up to Week 52 | 
| Proportion of subjects who achieve a ≥ 4-point reduction in DLQI from baseline | The DLQI is a dermatology-specific quality of life (QoL) instrument designed to assess the impact of the disease on a participant's QoL. It is a 10-item questionnaire that, in addition to evaluating overall Qol, can be used to assess six different aspects that mey affect QoL: 1) symptoms and feelings, 2) daily activities, 3) leisure, 4) work or school performance, 5) personal relationships, and 6) treatment. | Up to Week 52 | 
| Proportion of subjects who achieve Physician Global Assessment (PGA) of clear or almost clear (0 or 1) after treatment |  | Up to Week 52 | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of AK101 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs) | Up to Week 52 | 
| Minimum observed concentration (Cmin) of AK101 at steady state |  | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IL12/23