A Randomized, Double-blind, Placebo-controlled, Phase II, Multicenter Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacokinetics of Subcutaneous JS005 in Chinese Adult Patients With Active Ankylosing Spondylitis

Shanghai Junshi Bioscience Co., Ltd.23 sites in 1 country120 target enrollmentDecember 10, 2021

ConditionsActive Ankylosing Spondylitis

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Active Ankylosing Spondylitis
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Enrollment: 120
Locations: 23
Primary Endpoint: Primary efficacy endpoint
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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 Ankylosing Spondylitis. Treatment difference of JS005 150mg,300mg,450mg vs. placebo in Chinese AS patients in terms of ASAS 20 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 AS from Week 16 on.

Registry

clinicaltrials.gov

Start Date

December 10, 2021

End Date

January 11, 2023

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Shanghai Junshi Bioscience Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have an established diagnosis of AS according to Modified New York criteria for AS in 1984, and active AS assessed by total BASDAI ≥ 4 (0-10 point scale) and spinal pain ≥ 4 （according to the 0-10 NRS scale ( BASDAI question #2) at baseline.
•Voluntarily participate in this clinical trial and sign the informed consent form.
•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 patients and their female partners of childbearing age must agree to use reliable contraception during the study.
•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.
•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.
•Patients using tumor necrosis factor α (TNFα) inhibitors must have experienced an inadequate response to the standard treatment doses for at least 3 months, or have been intolerant to anti-TNFα agents.
•Patients who have previously been on a TNFα inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization (e.g., washout periods of 4 weeks for etanercept, 8 weeks for infliximab, and 10 weeks for adalimumab, golimumab, and certolizumab, respectively).
•Patients taking Methotrexate (MTX) (≤ 25 mg/week) or sulfasalazine (SSZ) ( ≤ 3 g/day) are allowed to continue their medication and must have taken it for at least 3 months and be on a stable dose for at least 4 weeks prior to randomization. Patients taking MTX need to take folic acid supplements.
•Patients who are on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) other than MTX and sulfasalazine must discontinue the csDMARDs 4 weeks prior to randomization, except for leflunomide (LEF), which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine washout has been performed.
•Patients taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day prednisone or equivalent for at least 2 weeks prior to randomization

Exclusion Criteria

•Patients with total ankylosis of the spine or imaging (X-ray) with the evidence of sacroiliitis with complete fusion of sacroiliac joints.
•Previous exposure to JS005 or any other biologic drug directly targeting IL-17 or IL-17 receptors.
•Have taken high potency analgesics (e.g., opiates of methadone, hydromorphone, morphine) within 2 weeks prior to randomization.
•Previous treatment with any intra-articular injection (e.g., glucocorticoids) within 4 weeks prior to randomization.
•Previous treatment with any biological immunomodulating agents other than the TNFα inhibitors.
•Treatment with JAK inhibitor agents within 8 weeks prior to randomization and unwilling to discontinue during the study.
•Patient unwilling to take folic acid/leucovorin to reduce MTX toxicity.
•Has received any cell-depletion therapies including but not limited to anti-CD20 antibodies, or investigational agents (e.g., Campath, anti-CD4 , anti-CD5, anti-CD3, anti-CD19).
•Previous treatment with traditional Chinese medicine or animal and plant extracts for AS within 4 weeks prior to randomization.
•Use of any investigational agents and/or devices within 4 weeks prior to randomization or within 5 half-lives of the investigational drug, whichever is longer.

Outcomes

Primary Outcomes

Primary efficacy endpoint

Time Frame: From week 0 to week 16

The proportion of AS patients meeting the Assessment of Spondylo Arthritis international Society 20 (ASAS20) response criteria at the end of treatment Week 16.

Secondary Outcomes

ASAS40 response criteria(From week 0 to week 16)
ASAS 5/6 response criteria(From week 0 to week 16)
High-sensitivity C-reactive protein (hsCRP)(From week 0 to week 16)
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(From week 0 to week 16)
Bath Ankylosing Spondylitis Functional Index (BASFI)(From week 0 to week 16)
Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL)(From week 0 to week 16)
Bath Ankylosing Spondylitis Disease Metrology Index (BASMI)(From week 0 to week 16)
The proportion of patients meeting the ASAS partial remission criteria(From week 0 to week 16)
nkylosing Spondylitis Disease Activity Score (ASDAS-CRP)(From week 0 to week 16)
The patient's global assessment of disease activity(From week 0 to week 16)
The patient's assessment of inflammatory back pain intensity(From week 0 to week 16)