Jaktinib Hydrochloride Tablets In The Treatment of Active Ankylosing Spondylitis

Study Overview
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Brief Summary
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This trial uses a multi-center, randomized, double-blind, placebo, parallel-controlled design, and it is expected that about 105 cases will be enrolled in about 10 sites.

Detailed Description
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The study is divided into two stages, the first stage (1-16 weeks) is the main study; the second stage (17-32 weeks) is the extended study. This study set up 3 groups:Jaktinib Hydrochloride Tablets 75mg Bid group, 100mg Bid group and a placebo control group. The subjects were randomly enrolled in the group 1:1:1.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo, Parallel-controlled Phase Ⅱ Clinical Trial of Jaktinib Hydrochloride Tablets in the Treatment of Patients With Active Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: Jaktinib Hydrochloride Tablets
* Drug: Jaktinib Hydrochloride Tablets
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65, both gender; Active Ankylosing Spondylitis; Participants who have been treated with non-steroidal anti-inflammatory drugs(NSAIDs) and still have active disease, or Participants who are intolerant to NSAIDs and stop the drug; Participants receiving low-dose oral glucocorticoid therapy (≤10mg/d prednisone) should maintain a stable medication regimen for at least 4 weeks before the first dose of this study. Do not adjust the dose during the entire study period except in emergency situations. Participants receiving other non-prohibited co-drugs should maintain a stable medication regimen for at least 7 days before the first dose of this study; Understand and voluntarily signed informed consent. Exclusion Criteria: A history of known or suspected complete spinal rigidity, or clinical and imaging confirmed complete spinal rigidity; A history of any other autoimmune rheumatic disease; Any history of joint prosthesis infection, and the prosthesis is still in place; Participants who are using strong opioid analgesics (such as methadone, hydromorphone, morphine, etc.); Participants who have been treated with any JAK inhibitors (such as Tofacitinib, Baricitinib, Ruxolitinib, Filgotinib, Upadacitinib, etc.); Participants who have drug abuse or alcohol dependence; Participants who have had herpes virus infection in the past month; Participants who have a history of venous thrombosis (regardless of current treatment); Any significant clinical and laboratory abnormalities that the investigator believes will affect the safety evaluator； Participants who cannot be treated and followed up according to the trial protocol; Any Participant considered by the investigator to be unsuitable to participate in this clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Jaktinib 100mg<br>100 mg bid.po | Drug: Jaktinib Hydrochloride Tablets<br>* Morning: 1*75mg simulated tablet, 2*50mg Jaktinib Hydrochloride Tablets; Evening: 1*75mg simulated tablet, 2*50mg Jaktinib Hydrochloride Tablets.<br>* Other names: Jaktinib;|
| Experimental: Jaktinib 75mg<br>75 mg bid.po | Drug: Jaktinib Hydrochloride Tablets<br>* Morning: 2*50mg simulated tablets and 1*75mg Jaktinib Hydrochloride Tablets; Evening: 2*50mg simulated tablets and 1*75mg Jaktinib Hydrochloride Tablets.<br>* Other names: Jaktinib;|
| Placebo Comparator: Placebo<br>Placebo bid.po | Drug: Placebo<br>* Morning: 1*75mg simulated tablet, 2*50mg simulated tablets; Evening: 1*75mg simulated tablet, 2*50mg simulated tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving 20 Percent (%) Improvement in Assessment of SpondyloArthritis International Society (ASAS) Score (ASAS 20) at Week 16 | ASAS20 responder had improvement of greater than or equal to (≥) 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and less than or equal to (≤)1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Missing data were handled by nonresponsive (NRI)/ last observation carried forward (LOCF). Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving ASAS 20 at Week 2, 4, 8, 12, 20, 24, and 32 | It assess the disease activity. It was evaluated with a 6-question questionnaire. After taking the answer of each question out of 10, the total of the points was calculated by dividing the number of questions.The score range was 0-10, the low score meant that the spinal movement was better. | Week 2,4,8,12,16,20,24,32 | 
| Percentage of Participants Achieving ASAS 40 at Week 2, 4, 8, 12, 16, 20, 24, and 32 | ASAS 40 is defined as ≥40% and absolute change of ≥2 units in at least 3 domains on a 0-10 scale (0=no disease activity, 10=high disease activity), and no worsening in the remaining domain. Missing data were handled by NRI/LOCF. | Week 2,4,8,12,16,20,24,32 | 
| Percentage of Participants Achieving ASAS 70 at Week 2, 4, 8, 12, 16, 20, 24, and 32 | It characterises the spinal mobility of patients with ankylosing spondylitis. Cervical rotation, tragus-wall distance, lateral lumbar flexion, anterior lumbar flexion (modified schober), intermalleolar distance were measured. The score range was 0-10, the low score meant that the spinal movement was better. | Week 2,4,8,12,16,20,24,32 | 
| Percentage of Participants Achieving ASAS 5/6 Response at Weeks 2, 4, 8, 12, 16, 20, 24, and 32 | ASAS5/6 consists of 6 domains: the 4 used in ASAS20 (Patient's Global Assessment of Disease Activity, spinal pain, function, inflammation plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). ASAS 5/6 is defined as ≥20% improvement in at least 5 domains and no worsening in the remaining domain. Missing data were handled by NRI/LOCF. | Week 2,4,8,12,16,20,24,32 |