Study of Efficacy and Safety of GR1501 in Patients With Radiographic Axial Spondyloarthritis

Study Overview
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Brief Summary
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The purpose of this trial is to demonstrate the clinical efficacy of GR1501 at week 16; and to demonstrate safety and tolerability of GR1501 compared to placebo in patients with Radiographic Axial Spondyloarthritis at week 16 and long term safety up to Week 48。 The main question it aims to answer is whether GR1501 injection was superior to placebo in the proportion of subjects with ASAS20 response at week 16 in patients with Radiographic Axial Spondyloarthritis.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter clinical study to evaluate the efficacy and safety of GR1501 injection in Radiographic Axial Spondyloarthritis, as well as a confirmatory clinical trial of immunogenicity. This clinical trial was divided into four stages, namely screening period (W-4 W0), core treatment period (W0 W16), maintenance treatment period (W16 W32), and follow-up period (W32 W48). target population： radiographic axial spondyloarthritis who had a inadequate response to NSAIDs or have a history of intolerance to NSAIDs. primary outcome measure:percentage of participants achieving an ASAS20 response in week 16.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase III Study of Efficacy and Safety of GR1501 in Patients With Radiographic Axial Spondyloarthritis

Conditions
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Axial Spondyloarthritis

Intervention / Treatment
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* Biological: GR1501 low dose
* Biological: GR1501 high dose
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of radiographic axial spondyloarthritis (r-xSpA) with sacroiliitis defined radiographically according to the modified New York criteria. inadequate response, contraindications or intolerance to NSAIDs Exclusion Criteria: Total ankylosis of the spine Ongoing or serious infection 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

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 465 patients were randomly assigned to 100mg GR1501 injection, 200mg GR1501 injection, and placebo group at 1:1:1. Randomized stratification factors included history of biologic therapy and weight. After the completion of 16-week ,subjects in the GR1501 injection group continued to be administered GR1501 injection, and those in the placebo group were randomly assigned 1:1 to the 100mg GR1501 injection and 200mg GR1501 injection.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group 1<br>GR1501 low dose | Biological: GR1501 low dose<br>* 3×low dose GR1501 every 2 weeks,then low dose GR1501 monthly<br>|
| Experimental: Treatment group 2<br>GR1501 high dose | Biological: GR1501 high dose<br>* 3×high dose GR1501 every 2 weeks,then high dose GR1501 monthly<br>|
| Placebo Comparator: treatment group 3<br>placebo | Biological: placebo<br>* Core treatment period:placebo Maintenance treatment period: GR1501 injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Participants Who Achieve an ASAS 20 Response | ASAS20 response is defined as an improvement of ≥20% and ≥1 units in at least three of the four ASAS main domains | week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Participants Who Achieve an ASAS 20 Response | ASAS20 response is defined as an improvement of ≥20% and ≥1 units in at least three of the four ASAS main domains | week 2 to 48 | 
| The Proportion of Participants Who Achieve an ASAS 40 Response | ASAS40 response is defined as an improvement of ≥40% and ≥2 units in at least three of the four ASAS main domains | week 2 to 48 | 
| The Proportion of Participants Who Achieve an ASAS 5/6 Response | The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains | week 16，32，48 | 
| Change From Baseline in Mobility on the BASMI | 5 clinical measurements Bath Ankylosing Spondylitis Metrology Index | week 16，32，48 | 
| Change From Baseline in BASDAI Response | 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis | week 16，32，48 | 
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) | 10 questions to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities | week 16，32，48 | 
| Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) | The MASES assesses 13 sites for enthesitis using a score of 0 for no activity or 1 for activity | week 16，32，48 | 
| Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) | ASDAS is a composite index to assess disease activity in AS | week 16，32，48 | 

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