to Evaluate the Preliminary Efficacy and Safety of GR1501 Injection in Patients With Active Axial Spondyloarthritis

Study Overview
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Brief Summary
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Dosage: 100mg or 200mg or 300mg Administration frequency: Q2W administration in the first 4 weeks (W0, W2, W4), and subsequent Q4W administration (W8, W12) Administration: subcutaneous injection Specifications: 100mg/ 1mL/bottle or placebo 0mg/1ml/ bottle

Detailed Description
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This is a randomized, double-blind, placebo-controlled phase II clinical trial evaluating the preliminary efficacy, safety, pharmacokinetic, and immunogenicity of GR1501 injection (IL-17A antiboby) at different doses and dosing frequency in patients with active axial spinal arthritis. A total of 160 patients were enrolled in the planned trial, and after passing the screening period of 2 weeks, they were randomly assigned to the 100mg group, 200mg group, 300mg group or placebo group according to 1:1:1:1.After the completion of the 16-week administration period, the follow-up period ( 24 weeks) was initiated.

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Preliminary Efficacy, Safety, Pharmacokinetics and Immunogenicity Characteristics of GR1501 Injection by in Patients With Active Axial Spondyloarthritis

Conditions
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Axial Spondyloarthritis

Intervention / Treatment
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* Biological: IL-17A antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: According with the diagnosis of axial spondyloarthritis (axSpA) by the Assessment of Spondyloarthritis International Society (ASAS);, During the screening period, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 points and the Spinal Pain (BASDAI Article 2) NRS score ≥ 4 points; Exclusion Criteria: Previous or current Crohn's disease; Suffering from ulcerative enteritis and requiring immunosuppressive therapy at present;

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
Interventional Model Description: A total of 160 patients were enrolled in the planned trial, and after passing the screening period of 2 weeks, they were randomly assigned to the 100mg group, 200mg group, 300mg group or placebo group according to 1:1:1:1. After the completion of the 16-week administration period, the follow-up period ( 24 weeks) was initiated.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group 1<br>Drug：GR1501 100mg | Biological: IL-17A antibody<br>* Recombinant fully human IgG4 anti-IL-17A monoclonal antibody drug<br>|
| Experimental: Treatment group 2<br>Drug：GR1501 200mg | Biological: IL-17A antibody<br>* Recombinant fully human IgG4 anti-IL-17A monoclonal antibody drug<br>|
| Experimental: Treatment group 3<br>Drug：GR1501 300mg | Biological: IL-17A antibody<br>* Recombinant fully human IgG4 anti-IL-17A monoclonal antibody drug<br>|
| Placebo Comparator: Treatment group 4<br>Drug：placebo | Biological: IL-17A antibody<br>* Recombinant fully human IgG4 anti-IL-17A monoclonal antibody drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASAS 20 responder | clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of 20% or more and absolute improvement of at least 1 units (on a scale of 0 [least] to 10 [worst]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (worsening of at least 20% an absolute Worsening of at least 1 unit) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASAS 40 responder | Number of Participants Who Achieved ASAS40，ASAS40 responder had improvement of 40% or more and absolute improvement of at least 2 units (scale of 0 [least] to 10 [worst]) from Baseline in at least 3 of the following 4 domains, with no deterioration in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores) | Week 2, 4, 8, 12, 16, 20, 24 | 
| ASAS 5/6 responder | Number of Participants Who Achieved ASAS5/6，ASAS 5/6 responder had improvement of 20% or more) from Baseline in at least 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores); Spinal Mobility (BASFI); Acute phase reactant (CRP) | Week 12, 16, 24 | 
| Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score | BASMI measures the range of motion based on five clinical measurements: 1) cervical rotation, 2) tragus to wall distance, 3) lumbar side flexion, 4) lumbar flexion (modified Schober's) and 5) intermalleolar distance. BASMI 0 = indicates mild disease involvement, 1 = moderate disease, and 2 = severe disease involvement. The results for cervical rotation and lumbar side flexion are the means of the left and right measurements. Scoring range 0-10. The higher the BASMI score, the more severe was the subject's limitation of movement | Week 2, 4, 8, 12, 16, 20, 24 | 
| 17. Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | The BASDAI consists of a 1 through 10 scale (1 being no problem and 10 being the worst problem), which was used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain / swelling, areas of localized tenderness (called enthesitis, or inflammation of insertion sites of tendons and ligaments), morning stiffness duration, and morning stiffness severity. The physician will globally assess the subject's current disease state | Week 2, 4, 8, 12, 16, 20, 24 | 
| Magnetic Resonance Imaging (MRI) Inflammatory Scores | The study used MRI with fat-saturating techniques such as short tau inversion recovery (STIR) to look for the presence of bone marrow edema. The Berlin modification of ASspiMRI-a (ASspiMRI-a) scoring technique assesses inflammation in each of the 23 disc vertebral units (DVU), capturing edema and erosion. Scores for each DVU range from 0-3 (0=normal; 1=minor bone marrow edema (less than25% of DVU; 3=severe bone marrow edema (more that 50% of DVU). The composite score ranges from 0 to 69, with higher scores indicating more severe inflammation | Week 16, 24 | 
| Number of adverse events to measure Safety of subcutaneously administered GR1501 | Safety of GR1501 s.c. injection will be documented as numbers of adverse event | to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IL-17A, Axial Spondyloarthritis