Evaluate the Preliminary Efficacy, Safety, and PK of Subcutaneous JS005 in Chinese Adult Patients With Active Nr-axSpA

Non-radiographic Axial Spondyloarthritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05242588
• Other study ID #: JS005-004-II-nr-axSpA
• Status: Recruiting
• Phase: Phase 2
• Start date: January 26, 2022
• Est. completion date: June 10, 2023

Study information

• Verified date: February 2022
• Source: Shanghai Junshi Bioscience Co., Ltd.
• Contact: Chengbo Jia, Bachelor
• Phone: 861085172616/18547265054
• Email: chengbo_jia[@]junshipharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 10, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 a (TNFa) inhibitors must have experienced an inadequate response to the standard treatment dose for at least 3 months, or have been intolerant to TNFa 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 TNFa inhibitors.

6. Treatment with JAK inhibitor agents within 8 weeks prior to randomization and unwilling to discontinue during the study.

Related Conditions & MeSH terms

• Non-radiographic Axial Spondyloarthritis
• Spondylarthritis

Intervention

Biological:
• JS005
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).
• Placebo
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).

Locations

Country	Name	City	State
China	The First Hospital of Jilin University	Changchun	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The Second Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Nanfang Hospital of Nanfang Medical University	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Sun Yat-sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Zhejiang University,School of Medicine	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The Affilated Hospital of Inner Mongdlia Medical University	Hohhot	Inner Mongolia
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	North Sichuan Medical College Affiliated Hospital	Nanchong	Sichuan
China	Shanghai Changzheng Hospital	Shanghai	Shanghai
China	Shantou University Medical Collge No.1 Affiliated Hospital	Shantou	Guangdong
China	Shengjing Hospital of China medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	Pking University Shenzhen Hospital	Shenzhen	Guangdong
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	First Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	People's Hospital of Xinjiang Uygur Autonomous Region	Urumqi	Xinjiang
China	Tongji Hospital,Tongji Medical College of HUST	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Junshi Bioscience Co., Ltd.	Sponsor GmbH

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic endpoint	• Population pharmacokinetic analysis of plasma concentrations will be performed to explore the exposure of JS005 in patients and the influencing factors of exposure	From Baseline to week 24,Total 24 weeks
Other	Pharmacodynamic endpoint	• Concentrations and the changes of free and/or total IL-17 in serum before and after administration.	From Baseline to week 24,Total 24 weeks
Other	Immunogenicity endpoint	• Anti-drug antibody (ADA), for the ADA positive samples, it is necessary to test the titer and determine whether it is a neutralizing antibody (Nab).	From Baseline to week 24,Total 24 weeks
Other	Safety evaluation	Safety evaluation will be documented as numbers of adverse event(AE).	From V1 to V12, Total 36 Weeks
Primary	The proportion of nr-axSpA patients meeting the Assessment of Spondylo Arthritis international Society (ASAS) 40 response criteria	at the end of treatment Week 16 .	From week 0 to week 16
Secondary	ASAS20 response criteria	The proportion of patients meeting the ASAS20 response criteria at the end of treatment Week 16	From week 0 to week 16
Secondary	ASAS 5/6 response criteria	The proportion of patients meeting the ASAS 5/6 response criteria at the end of treatment Week 16;	From week 0 to week 16
Secondary	High-sensitivity C-reactive protein (hsCRP)	The change from baseline in high-sensitivity C-reactive protein (hsCRP) at the end of treatment Week 16	From week 0 to week 16
Secondary	The inflammation score of the sacroiliac joint	The change from baseline in the inflammation score of the sacroiliac joint by MRI at the end of treatment Week 16	From week 0 to week 16
Secondary	Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP)	The change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) at the end of treatment Week 16;	From week 0 to week 16
Secondary	Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)	The change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at the end of treatment Week 16	From week 0 to week 16
Secondary	Bath Ankylosing Spondylitis Functional Index (BASFI)	The change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at the end of treatment Week 16	From week 0 to week 16
Secondary	Bath Ankylosing Spondylitis Disease Metrology Index (BASMI)	The change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at the end of treatment Week 16	From week 0 to week 16
Secondary	Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL)	The change from baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) at the end of treatment Week 16	From week 0 to week 16
Secondary	The patient's global assessment of disease activity	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?	From week 0 to week 16
Secondary	The patient's assessment of inflammatory back pain intensity	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.	From week 0 to week 16
Secondary	ASAS partial remission criteria	The proportion of patients meeting ASAS partial remission criteria at the end of treatment Week 16	From week 0 to week 16