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

Brief Title

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

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 Adult Patients With Active Ankylosing Spondylitis

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Primary efficacy endpoint

Secondary Outcome

 ASAS40 response criteria

Condition

Active Ankylosing Spondylitis

Intervention

JS005

Study Arms / Comparison Groups

 JS005 150 mg
Description:  30 patients will be enrolled in this arm.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

120

Start Date

December 10, 2021

Completion Date

January 11, 2023

Primary Completion Date

November 2, 2022

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Voluntarily participate in this clinical trial and sign the informed consent form.

          3. 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.

          4. 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.

          5. 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.

          6. 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.

          7. 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).

          8. 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.

          9. 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.

         10. 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:

          1. Patients with total ankylosis of the spine or imaging (X-ray) with the evidence of
             sacroiliitis with complete fusion of sacroiliac joints.

          2. Previous exposure to JS005 or any other biologic drug directly targeting IL-17 or
             IL-17 receptors.

          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.

          7. Patient unwilling to take folic acid/leucovorin to reduce MTX toxicity.

          8. 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).

          9. Previous treatment with traditional Chinese medicine or animal and plant extracts for
             AS within 4 weeks prior to randomization.

         10. 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.

         11. Females who are pregnant or lactating.

         12. Chest imaging (e.g., x-ray or CT) with evidence of ongoing infectious or malignancy,
             obtained within 3 months prior to screening and evaluated by a qualified physician

         13. Active systemic infections (other than the common cold) within 2 weeks prior to
             randomization.

         14. Patients with other diseases other than ankylosing spondylitis that might confound the
             evaluation of the efficacy of JS005 therapy: such as chronic pain other than
             ankylosing spondylitis (such as fibromyalgia), inflammatory bowel disease, acute
             anterior uveitis, etc., within 6 weeks prior to randomization. However, patients with
             non-acute iritis and psoriasis that have been stable for 6 months or more can be
             included in this study.

         15. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurological, endocrine,
             cardiac, infectious, or gastrointestinal conditions which in the opinion of the
             investigator immunocompromises the patient and/or places the patient at unacceptable
             risk in case of using immunomodulatory therapy.

         16. Myocardial infarction, apoplexy, congestive heart failure (New York Heart Association
             status of class III or IV) within 6 months prior to screening; uncontrolled
             hypertension (≥ 160/95 mmHg) prior to randomization.

         17. Patients with type 1 diabetes mellitus, or newly diagnosed or uncontrolled type 2
             diabetes mellitus (e.g., HbA1C > 9.0%) within 6 months prior to screening.

         18. Patients with active liver disease or hepatic insufficiency, with any of the following
             abnormalities in liver function tests at screening: alanine aminotransferase (ALT) or
             aspartate aminotransferase (AST) or total bilirubin > 1.5 × upper limit of normal.

         19. History of renal injury, glomerulonephritis, or patient with only one kidney or
             glomerular filtration rate < 60 mL/(min · 1.73 m2 ) at screening.

         20. Total white blood cell count < 3 × 109/L, or neutrophils < 1.5 × 109/L or absolute
             lymphocyte count < 0.5 × 109/L or hemoglobin < 8.5 g/dL or platelets < 100 × 109/L at
             screening.

         21. History of ongoing chronic or recurrent infectious disease, or evidence of
             tuberculosis infection on tuberculosis screening (X. DOT-TB, QuantiFERON TB-Gold,
             T-SPOT) (see Section 8.3.4 for details).

         22. Positive for human immunodeficiency virus antibody (Anti-HIV) at screening.

         23. Positive for hepatitis C virus antibody (Anti-HCV) at screening.

         24. HBV DNA is detected in patients with positive hepatitis B surface antigen (HBsAg) or
             hepatitis B core antibody (HBcAb) at screening (the lower limit of quantitative
             detection refers to the reference value of each hospital.).

         25. History of lymphoproliferative disease or malignancy within the past 5 years (except
             for basal cell carcinoma or actinic keratoses that have been treated with no evidence
             of recurrence in the past 3 months, and carcinoma in situ of the cervix or
             non-invasive malignant colon polyps that have been surgically removed ).

         26. Previous or medical history of other significant concomitant diseases that, in the
             judgment of the investigator, participation would not be in the best interest of the
             patient. These include, but are not limited to, cardiovascular disorder, nephropathy,
             neurological disease (including demyelinating disease), active infectious disease,
             endocrine disease, gastrointestinal disease, hepatobiliary disease, metabolic disease,
             pulmonary disease, non-malignant lymphoproliferative disease, or other lymphatic
             diseases.

         27. Surgery of the spine or joint or other major surgery (e.g., aneurysmectomy, gastric
             ligation) within 3 months prior to randomization or planned during the study.

         28. History or evidence of ongoing alcohol or drug abuse within 6 months prior to
             randomization.

         29. The patient has a history of systemic hypersensitivity to any biological agent,
             excluding injection site reactions.

         30. Vaccination with a live vaccine (live attenuated vaccine*) and BCG vaccine within 12
             weeks prior to randomization
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

, 861085172616/8618547265054, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT05212051

Organization ID

JS005-003-II-AS


Responsible Party

Sponsor

Study Sponsor

Shanghai Junshi Bioscience Co., Ltd.

Collaborators

 Sponsor GmbH

Study Sponsor

, , 


Verification Date

November 2021