A Clinical Study of AK101 in Subjects With Moderate to Severe 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 (PK), immunogenicity, pharmacodynamics (PD) and the preliminary efficacy of AK101，an anti-IL-12/23p40 monoclonal antibody, when administered subcutaneously in subjects with moderate-to-severe plaque psoriasis.

Detailed Description
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This was a single-center, randomized, double-blind, placebo-controlled trial which consisted of a dose escalation phase (Phase I) and a dose expansion phase (Phase II)..

Official Title
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A Randomized, Double-blinded, and Placebo-controlled Phase I/II 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. Patients who have received systemic therapy or phototherapy, or who have been allowed by the investigator to receive systemic therapy or phototherapy. 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 dose 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. History of alcohol or drug abuse. History or known presence of recurrent or chronic infection (e.g., hepatitis B, 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 previous treatment with 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: 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I: AK101 45 mg<br>Biological: AK101 AK101 45 mg on Week 0 and 4 by subcutaneous injection | Biological: AK101<br>* AK101 is an anti-IL-12/23p40 monoclonal antibody.<br>|
| Experimental: Phase I: AK101 135 mg<br>Biological: AK101 AK101 135 mg on Week 0 and 4 by subcutaneous injection | Biological: AK101<br>* AK101 is an anti-IL-12/23p40 monoclonal antibody.<br>|
| Experimental: Phase I: AK101 270 mg<br>Biological: AK101 AK101 270 mg on Week 0 and 4 by subcutaneous injection | Biological: AK101<br>* AK101 is an anti-IL-12/23p40 monoclonal antibody.<br>|
| Placebo Comparator: Phase I: Placebo<br>Biological: Placebo Placebo on Week 0 and 4 by subcutaneous injection | Biological: placebo<br>* matching placebo<br>|
| Experimental: Phase II: AK101 45 mg<br>Biological: AK101 AK101 45 mg on Week 0, 4 and 16 by subcutaneous injection | Biological: AK101<br>* AK101 is an anti-IL-12/23p40 monoclonal antibody.<br>|
| Experimental: Phase II: AK101 90 mg<br>Biological: AK101 AK101 90 mg on Week 0, 4 and 16 by subcutaneous injection | Biological: AK101<br>* AK101 is an anti-IL-12/23p40 monoclonal antibody.<br>|
| Experimental: Phase II: AK101 135 mg<br>Biological: AK101 AK101 135 mg on Week 0, 4 and 16 by subcutaneous injection | Biological: AK101<br>* AK101 is an anti-IL-12/23p40 monoclonal antibody.<br>|
| Placebo Comparator: Phase II: Placebo to AK101<br>Drug: Placebo Placebo on Week 1 and 4 by subcutaneous injection, and then AK101 on Week 12 16 by subcutaneous injection | Biological: AK101<br>* AK101 is 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 |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) |  | From the time of signing informed consent till Week 16 for Phase I or Week 28 for Phase II | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75) |  | At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II) | 
| Number of participants who achieved ≥ 90% reduction in PASI (PASI90) |  | At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II) | 
| Change From Baseline in the Physician Global Assessment (PGA) |  | At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II) | 
| 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). | From first dose till Week 16 for Phase I or Week 28 for Phase II | 
| Area under the curve (AUC) of AK101 | The endpoints for assessment of PK of AK101 include serum concentrations of AK101 at different timepoints after AK101 administration. | From first dose till Week 16 for Phase I | 
| Minimum observed concentration (Cmin) of AK101 | The endpoints for assessment of PK of AK101 include serum concentrations of AK101 at different timepoints after AK101 administration. | From first dose till Week 16 for Phase I or Week 28 for Phase II | 
| Maximum observed concentration (Cmax) of AK101 | The endpoints for assessment of PK of AK101 include serum concentrations of AK101 at different timepoints after AK101 administration. | From first dose till Week 16 for Phase I or Week 28 for Phase II | 

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