Safety, Tolerability and PK of SHR1314 in axSpA

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety, Tolerability and Pharmacokinetics (PK) of SHR1314 with axial spondyloarthritis.

Detailed Description
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This was a phase I, multicenter, double-blind, randomized, placebo-controlled study. The study originally planned to enroll 5 cohorts of 8 subjects each (N=40).

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, MAD Study to Evaluation of Safety, Tolerability and PK of SHR1314 With Axial Spondyloarthritis

Conditions
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Axial Spondyloarthritis

Intervention / Treatment
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* Drug: SHR-1314


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of axial spondyloarthritis (axSpA) and fulfilling the 2009 ASAS classification criteria. Have a history of back pain ≥3 months with age at onset <45 years. Have active axSpA defined as BASDAI ≥4 at screening and baseline. Have objective signs of inflammation by presence of elevated ESR and/or presence of elevated CRP. In the past had an inadequate response to at least 1 or 2 non-steroidal anti-inflammatory drugs (NSAIDS) for duration of 4 weeks or cannot tolerate NSAIDS. If taking NSAIDS be on stable dose for at least 2 weeks prior to randomization. Exclusion Criteria: History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection. Previous exposure to other biologic drug directly targeting Interleukin (IL)-17 or Interleukin (IL)-17 receptor. Total ankylosis of the spine. Have recently received biologics, tumor necrosis factor inhibitors or other immunomodulatory agents within 12 weeks. Have either a current diagnosis or a recent history of malignant disease. Are pregnant or breastfeeding.

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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Multiple subcutaneous injections of SHR-1314 dose 1 | Drug: SHR-1314<br>* Pharmaceutical form: Injection solution. Route of administration: subcutaneous injection.<br>* Other names: Placebo;|
| Experimental: Cohort 2<br>Multiple subcutaneous injections of SHR-1314 dose 2 | Drug: SHR-1314<br>* Pharmaceutical form: Injection solution. Route of administration: subcutaneous injection.<br>* Other names: Placebo;|
| Experimental: Cohort 3<br>Multiple subcutaneous injections of SHR-1314 dose 3 | Drug: SHR-1314<br>* Pharmaceutical form: Injection solution. Route of administration: subcutaneous injection.<br>* Other names: Placebo;|
| Experimental: Cohort 4<br>Multiple subcutaneous injections of SHR-1314 dose 4 | Drug: SHR-1314<br>* Pharmaceutical form: Injection solution. Route of administration: subcutaneous injection.<br>* Other names: Placebo;|
| Experimental: Cohort 5<br>Multiple subcutaneous injections of SHR-1314 dose 5 | Drug: SHR-1314<br>* Pharmaceutical form: Injection solution. Route of administration: subcutaneous injection.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability of multiple subcutaneous injections of SHR1314 in adult patients with axial spondyloarthritis 1.Incidence of Treatment-Emergent Adverse Events 2.Incidence of Injection site reaction | Safety and tolerability of multiple subcutaneous injections of SHR1314 assessed by adverse events and serious adverse events. Incidence of Treatment-Emergent Adverse Events Incidence of Injection site reaction | Baseline to 169 days after dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) of SHR-1314 | maximum concentration (Cmax) | Baseline to 169 days after dose administration | 
| Time to maximum observed serum concentration (tmax) of SHR-1314 | Time to maximum concentration (Tmax) | Baseline to 169 days after dose administration | 
| Time to elimination half-life (t1/2) of SHR-1314 | t1/2 | Baseline to 169 days after dose administration | 
| Assessment of development of Anti-drug Antibodies (ADAs) | Incidence of development of Anti-drug Antibodies (ADAs) | Baseline to 169 days after dose administration | 
| Proportion of Participants Achieving an ASAS20 Response | ASAS20 Response | Week2, 4, 6, 8, 12,16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR1314