Clinical trial NCT05212051: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Active Ankylosing Spondylitis
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
Collaborators: name: Sponsor GmbH
First posted: 2022-01-27
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 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.

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

Primary outcomes:
measure: Primary efficacy endpoint
timeFrame: From week 0 to week 16
Secondary outcomes:
measure: ASAS40 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: 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: Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL)
timeFrame: From week 0 to week 16
measure: Bath Ankylosing Spondylitis Disease Metrology Index (BASMI)
timeFrame: From week 0 to week 16
measure: The proportion of patients meeting the ASAS partial remission criteria
timeFrame: From week 0 to week 16
measure: nkylosing Spondylitis Disease Activity Score (ASDAS-CRP)
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
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: Beijing
country: China
facility: Beijing University
state: Beijing
city: Shamen
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 City: Guangzhou
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Nandang Medical University
state: Guangdong
city: Shantou
country: China
facility: Shantou University Medical Collge No.1 Affiliated Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Pking University Shenzhen Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Gudong
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Hebei
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 Mongolia 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: Shengyang
country: China
facility: Shengjing Hospital of China medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Taiyuan
country: China
facility: The 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: Chuanbei Meidical College Affiliated Hospital
state: Sichuan
city: Urumqi
country: China
facility: People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang
Study officials:
References: