A Safety Study of Multiple Subcutaneous (s.c.) Injections of SHR-1314 in Adults With Moderate-to-severe Plaque Psoriasis

Study Overview
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Brief Summary
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This is a multiple dose escalating and open labeled clinical trial to evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple subcutaneous (s.c.) injections of SHR-1314 in adults with moderate-to-severe plaque psoriasis. The primary objective of this study is to investigate the safety and tolerability of multiple doses of subcutaneous SHR-1314 in subjects with moderate-to-severe plaque psoriasis. Secondary objectives are to determine the pharmacokinetics (PK) and immunogenicity profile of SHR-1314 in subjects with moderate-to-severe plaque psoriasis.

Detailed Description
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16 subjects with 2 dose groups will be enrolled in the study, all of whom received the SHR-1314 without placebo control. There are 8 subjects in each cohort. The dose will be started at 160mg and will be escalated by following dose escalating rules. The primary endpoint is the safety and tolerability : adverse events, vital signs, physical examination, laboratory examination, 12 lead electrocardiogram, injection site reactions, etc.

Official Title
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Safety, Tolerability and Pharmacokinetics Studies Following Multiple Subcutaneous Injections of SHR-1314 in Adults With Moderate-to-severe Plaque Psoriasis

Conditions
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Moderate-to-severe Plaque Psoriasis

Intervention / Treatment
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* Biological: SHR-1314


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female at age between 18 and 65 years old at screening. History of chronic plaque-type psoriasis for at least 6 months, with either documented medical history of psoriasis for at least 6 months or confirmation of the diagnosis by the Investigator at screening, if the subject was diagnosed by another physician. At the time of randomization, moderate to severe plaque psoriasis, defined by: PASI score of 12 or greater and PGA score of 3 or greater and BSA affected by plaque-type psoriasis of 10% or greater. A subject is a candidate for systemic psoriasis therapy and/or phototherapy and/or chemo phototherapy. Body Mass Index (BMI) of 18 to 35 kg/m2 (inclusive) at screening. Exclusion Criteria: Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic, and guttate psoriasis) at screening. Drug-induced psoriasis (i.e. new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at randomization. Active systemic infections (other than common cold) during the two weeks before randomization (e.g., hepatitis), or serious infections requiring hospitalization and/or intravenous injection of antibiotic treatment within eight weeks prior to randomization. History of inflammatory bowel disease or have other ongoing active autoimmune diseases. At screening, history or symptoms of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. History of depression and/or suicidal ideation or any suicidal behavior based on clinical assessment by the investigator. Have a known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study. Are currently enrolled in, or discontinued from a clinical trial involving an IP within the last 4 weeks or at least 5 half-lives of the last dosing prior to randomization, whichever is longer; or concurrently enrolled (at randomization) in any other trials. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test at screening or Day 0. Females of childbearing potential (defined as all females physiologically capable of becoming pregnant) and males who are unwilling or unable to use highly effective contraception during the study and 21 weeks after the last administration of IP (anticipated 5 half-lives). History of alcohol or illicit drug abuse within the year prior to screening. Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the Investigator.

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Multiple subcutaneous injections of SHR-1314 at 160mg every two weeks | Biological: SHR-1314<br>* Pharmaceutical form: Injection solution. Route of administration: subcutaneous injection.<br>|
| Experimental: Cohort 2<br>Multiple subcutaneous injections of SHR-1314 at 240mg every two weeks | Biological: SHR-1314<br>* Pharmaceutical form: Injection solution. Route of administration: subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of Treatment-Emergent Adverse Events [Safety and tolerability] | Incidence and severity of adverse events, change from baseline in vital signs and 12-lead electrocardiogram. | Baseline to 168 days after first dose administration | 
| Incidence of development of Anti-drug Antibodies (ADAs) [Safety and Tolerability] | Incidence of development of Anti-drug Antibodies (ADAs) during the course of the study. | Baseline to 168 days after first dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter | time to maximum concentration (tmax) | Baseline to 168 days after first dose administration | 
| Assessment of PK parameter | maximum concentration (Cmax) | Baseline to 168 days after first dose administration | 
| Assessment of PK parameter | area under curve (AUC0-14days) | Baseline to 168 days after first dose administration | 
| Assessment of development of Anti-drug Antibodies (ADAs) | Incidence of development of Anti-drug Antibodies (ADAs) | Baseline to 168 days after first dose administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR-1314 Phase 1