Non-radiographic Axial Spondyloarthritis
Conditions
Brief summary
The purpose of this study is to evaluate preliminary efficacy, safety pharmacokinetic (PK) characteristics, pharmacodynamics (PD) haracteristics and immunogenicity of JS005 at different doses in Chinese patients with active non-radiographic axial spondyloarthritis(nr-axSpA). Treatment difference of JS005 150mg,300mg,450mg vs. placebo in Chinese nr-axSpA patients in terms of ASAS 40 response rate at Week 16 as well as safety profile will be provided by the study .
Detailed description
This is a randomized, double-blind, placebo-controlled study. Approximately 120 patients who meet the eligibility criteria will be randomized to one of three treatment cohorts (JS005 150 mg, 300 mg, 450mg in a ratio of 1:1:1),then using secondary randomization method, 40 patients in each group will be randomized in a 3: 1 ratio to receive investigational product or placebo. 1. JS005 150mg Cohort: JS005 150 mg or placebo treatment(JS005:Placrbo=3:1) s.c. prefilled syringe (PFS) on Week 0, 1, 2, 3, 4,8 and 12 2. JS005 300mg Cohort: JS005 300 mg or placebo treatment(JS005:Placrbo=3:1) s.c. PFS on Week0, 1, 2 ,3, 4,8,and 12 3 .JS005 450mg Cohort: JS005 450 mg or placebo treatment(JS005:Placrbo=3:1) s.c. PFS on Week0, 1, 2 ,3, 4,8,and 12 Based on the clinical judgment of disease activity by the investigator and the patient, background medications, such as NSAIDs and DMARDs, may have been modified or added to treat signs and symptoms of nr-axSpA from Week 16 on.
Interventions
BIOLOGICALJS005
30 subjectes in JS005 150mg chort, JS005 300mg chort, and JS005 450mg chort receive JS005 150mg, JS005 300mg and JS005 450mg subcutaneous injection seperately at Week 0, 1, 2, and 3, and monthly dose starting at Week 4 (dosing in Week 4, 8, and 12).
BIOLOGICALPlacebo
10 subjects in JS005 150mg chort, JS005 300mg chort, and JS005 450mgchort receive the placebo subcutaneous injection seperately at Week 0, 1, 2, and 3, and monthly dose starting at Week 4 (dosing in Week 4, 8, and 12).
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Sponsor GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Priticipant,Care provider and investigators are masked in this study
Intervention model description
Parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who do not meet the modified New York criteria for AS in 1984; Meet the 2009 axSpA classification criteria recommended by International Assessment Society of Axial Spondyloarthritis (ASAS): inflammatory back pain for at least 3 months; Age of onset \< 45 years; Sacroiliitis on MRI with≥ 1 axial spondyloarthritis features or HLA-B27 positive with ≥ 2 SpA features (MRI and X-ray of sacroiliac joint as confirmed by central readers). 2. Objective signs of inflammation at screening: active inflammation of the sacroiliac joints on MRI and/or high sensitivity C-reactive protein (hsCRP) \> upper limit of normal without other diagnoses to explain the MRI results or elevated hsCRP. 3. Active axSpA at screening and baseline: assessed by total Bath ankylosing spondylitis disease activity index (BASDAI) ≥ 4 (0-10 scale) and spinal pain ≥ 4 (according to the 0-10 NRS scale, BASDAI question #2). 4. Voluntarily participate in this clinical trial and sign the informed consent form. 5. Male or female aged between 18 and 65 years (both inclusive) at the time of signing informed consent. Female subjects of childbearing age are required to have a confirmed negative result of urine and/or serum pregnancy test performed within 3 days before randomization and agree to use reliable contraceptive measures during the study; Male subjects and their female partners of childbearing age must agree to use reliable contraception during the study. 6. Patients meet at least one of the following: 1) have an inadequate or ineffective response to NSAIDs, 2) have been intolerant to at least one dose of NSAIDs, 3) have contraindications to NSAIDs therapy. Inadequate or ineffective response to NSAIDs is defined as no remission after continuous treatment with standard doses of at least 2 NSAIDs for a total of no less than 4 weeks and no less than 2 weeks for each NSAID. 7. Patients regularly taking NSAIDs as part of their AS therapy are required to maintain a stable dose for at least 2 weeks prior to randomization. 8. Patients using tumor necrosis factor α (TNFα) inhibitors must have experienced an inadequate response to the standard treatment dose for at least 3 months, or have been intolerant to TNFα inhibitors.
Exclusion criteria
1. Unable or unwilling to undergo MRI. 2. Previous exposure to JS005 or any other biologic drug directly targeting IL-17 or IL-17 receptor. 3. Have taken high potency analgesics (e.g., opiates of methadone, hydromorphone, morphine) within 2 weeks prior to randomization. 4. Previous treatment with any intra-articular injection (e.g., glucocorticoids) within 4 weeks prior to randomization. 5. Previous treatment with any biological immunomodulating agents other than the TNFα inhibitors. 6. Treatment with JAK inhibitor agents within 8 weeks prior to randomization and unwilling to discontinue during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of nr-axSpA patients meeting the Assessment of Spondylo Arthritis international Society (ASAS) 40 response criteria | From week 0 to week 16 | at the end of treatment Week 16 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ASAS20 response criteria | From week 0 to week 16 | The proportion of patients meeting the ASAS20 response criteria at the end of treatment Week 16 |
| ASAS 5/6 response criteria | From week 0 to week 16 | The proportion of patients meeting the ASAS 5/6 response criteria at the end of treatment Week 16; |
| High-sensitivity C-reactive protein (hsCRP) | From week 0 to week 16 | The change from baseline in high-sensitivity C-reactive protein (hsCRP) at the end of treatment Week 16 |
| The inflammation score of the sacroiliac joint | From week 0 to week 16 | The change from baseline in the inflammation score of the sacroiliac joint by MRI at the end of treatment Week 16 |
| Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) | From week 0 to week 16 | The change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) at the end of treatment Week 16; |
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | From week 0 to week 16 | The change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at the end of treatment Week 16 |
| Bath Ankylosing Spondylitis Functional Index (BASFI) | From week 0 to week 16 | The change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at the end of treatment Week 16 |
| Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) | From week 0 to week 16 | The change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at the end of treatment Week 16 |
| Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) | From week 0 to week 16 | The change from baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) at the end of treatment Week 16 |
| The patient's global assessment of disease activity | From week 0 to week 16 | Numeric Rating Scale (NRS, ranging from 0 not active to 10 very active) will be used to evaluate the patient's global assessment of disease activity. Patient will be asked by one question: How active was your spondylitis on average during the last week？ |
| The patient's assessment of inflammatory back pain intensity | From week 0 to week 16 | NRS(ranging from 0 no pain to 10 most severe pain) will be used to assess the patient's inflammatory back pain intensity. The assessment is based on two questions: "Based on your assessment, please indicate How much pain of your spine due to AS do you have ?" and "Based on your assessment, please specify How much pain of your spine due to AS do you have at night?" When responding, the subject is to consider the average amount of pain in the last week. |
| ASAS partial remission criteria | From week 0 to week 16 | The proportion of patients meeting ASAS partial remission criteria at the end of treatment Week 16 |
Countries
China
Outcome results
None listed