Clinical trial NCT05242588: Evaluate the Preliminary Efficacy, Safety, and PK of Subcutaneous JS005 in Chinese Adult Patients With Active Nr-axSpA
Official title: A Randomized, Double-blind, Placebo-controlled, Phase II, Multicenter Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacokinetics of Subcutaneous JS005 in Chinese Adults With Active Non-radiographic Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-radiographic Axial Spondyloarthritis
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
Collaborators: name: Sponsor GmbH
First posted: 2022-02-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of nr-axSpA patients meeting the Assessment of Spondylo Arthritis international Society (ASAS) 40 response criteria
timeFrame: From week 0 to week 16
Secondary outcomes:
measure: ASAS20 response criteria
timeFrame: From week 0 to week 16
measure: ASAS 5/6 response criteria
timeFrame: From week 0 to week 16
measure: High-sensitivity C-reactive protein (hsCRP)
timeFrame: From week 0 to week 16
measure: The inflammation score of the sacroiliac joint
timeFrame: From week 0 to week 16
measure: Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP)
timeFrame: From week 0 to week 16
measure: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: From week 0 to week 16
measure: Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: From week 0 to week 16
measure: Bath Ankylosing Spondylitis Disease Metrology Index (BASMI)
timeFrame: From week 0 to week 16
measure: Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL)
timeFrame: From week 0 to week 16
measure: The patient's global assessment of disease activity
timeFrame: From week 0 to week 16
measure: The patient's assessment of inflammatory back pain intensity
timeFrame: From week 0 to week 16
measure: ASAS partial remission criteria
timeFrame: From week 0 to week 16
Other outcomes:
measure: Pharmacokinetic endpoint
timeFrame: From Baseline to week 24,Total 24 weeks
measure: Pharmacodynamic endpoint
timeFrame: From Baseline to week 24,Total 24 weeks
measure: Immunogenicity endpoint
timeFrame: From Baseline to week 24,Total 24 weeks
measure: Safety evaluation
timeFrame: From V1 to V12, Total 36 Weeks
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Nanfang Medical University
state: Guangdong
city: Shantou
country: China
facility: Shantou University Medical Collge No.1 Affiliated Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Pking University Shenzhen Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital,Tongji Medical College of HUST
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Hohhot
country: China
facility: The Affilated Hospital of Inner Mongdlia Medical University
state: Inner Mongolia
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The Second Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Taiyuan
country: China
facility: First Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Nanchong
country: China
facility: North Sichuan Medical College Affiliated Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Urumqi
country: China
facility: People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University,School of Medicine
state: Zhejiang
Study officials:
References: