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