A Phase I/Ⅱ Clinical Trial for Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in the Treatment of Ankylosing Spondylitis

A Phase I/Ⅱ Clinical Trial for HS_SW01 Cells Injection in the Treatment of Ankylosing Spondylitis

The goal of this clinical trial is to evaluate the safety, tolerability and efficacy of human umbilical cord mesenchymal stem cell injection (HS_SW01 cells injection) in patients with Ankylosing Spondylitis.

Participants will be required to sign the informed consent form and will only be assigned to the study and enrolled after undergoing a series of tests and meeting the inclusion and exclusion criteria of the protocol.

This clinical trial is a multicenter Phase I/II clinical trial, which includes two stages: Phase I dose-escalation and Phase II dose-expansion. The Phase I dose-escalation stage adopts a single-arm design and aims to evaluate the safety, tolerability and preliminary efficacy of HS_SW01 cells injection in patients with Ankylosing Spondylitis. The Phase II dose-expansion stage is a randomized, double-blind, controlled study designed to evaluate the safety and efficacy of HS_SW01 cells injection in patients with Ankylosing Spondylitis.

During the Phase I, the trial includes three dose groups: 1.0×10^6 cells/kg, 2.0×10^6 cells/kg and 2.0×10^6 cells/kg. Using a "3+3" dose-escalation design, each dose group will enroll 4 to 7 subjects in sequential order from the lowest to the highest dose level.

Eligible participants are patients with Ankylosing Spondylitis between 18 and 65 years of age inclusive, who satisfy all the inclusion criteria and do not meet any of the exclusion criteria.

Inclusion Criteria:

1. Age 18 to 65 years, inclusive, male or female.
2. Voluntarily sign the informed consent form and comply with the requirements of this study protocol.
3. Participants must have a documented diagnosis of ankylosing spondylitis (AS) based on the modified 1984 New York criteria, as follows: (a) Inflammatory back pain for ≥3 months, improving with activity but not relieved by rest;; (b) Limited spinal motion in the lumbar spine (sagittal and frontal planes); (c) chest expansion reduced relative to normal values for age and sex. (d):Sacroiliitis on imaging: bilateral grade II-IV or unilateral grade III-IV. Diagnosis of AS requires fulfillment of criterion (d) plus any one of criteria (a)-(c). The diagnosis must be confirmed at both the screening and baseline visits.
4. Participants must have active AS at screening and baseline, defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4.
5. Participants must have received conventional therapy and, prior to randomization, must meet at least one of the following criteria for the following criteria, as confirmed by the investigator: (a) inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs): ≥4 weeks of continuous therapeutic-dose NSAID if one agent used; or ≥2 weeks of therapeutic-dose NSAID for each of ≥2 agents; (b) intolerance to NSAIDs: Discontinuation of NSAIDs due to treatment-related adverse events (e.g., allergic reactions, gastrointestinal symptoms or signs); the 4-week treatment duration is not required. (c) Contraindication to NSAID therapy: History of NSAID allergy, active gastrointestinal ulcer, bleeding, or other contraindications.
6. Participants who have previously received at least two biologic disease-modifying antirheumatic drugs (bDMARDs) must have received recommended doses for at least 12 weeks prior to randomization with inadequate response, or have been intolerant to at least one bDMARD treatment (e.g., unable to continue due to adverse drug reactions, allergic reactions, or other reasons).
7. Participants receiving concomitant oral corticosteroids or NSAIDs must be on a stable dose for at least 14 days before the baseline visit. Participants receiving conventional synthetic DMARDs (cDMARDs) must be on a stable dose for at least 28 days prior to the baseline visit.
8. Female participants must: Be of non-childbearing potential, defined as postmenopausal for at least 1 year or surgically sterilized; OR, If of childbearing potential, agree to use strict contraceptive measures from the time of signed informed consent through at least 6 months after the last dose of study drug, and have a negative serum pregnancy test at screening.
9. Participants must be considered in good general health based on medical history and physical examination performed at screening, as judged by the investigator.
10. Participants must voluntarily agree to receive disease education and be willing to maintain correct posture and perform appropriate physical exercise.
11. Participants must be willing and able to complete all study procedures and follow-up visits.

Exclusion Criteria:

1. Hypersensitivity to any component of this product;
2. History of significant drug abuse or alcohol dependence currently or within the past 2 years;
3. Complete rigidity of the spine in the trial participant;
4. Undergone bone/joint/synovectomy surgery within 3 months prior to screening, or planned to undergo joint or spinal surgery during the trial period;
5. Participation in another clinical trial within 3 months prior to screening, or planned participation in another clinical trial;
6. Severe infection indicated by clinical and radiological data; patients positive for HIV, hepatitis C, syphilis, etc.; patients with tumors or a tendency to develop tumors; patients with severe cardiac, pulmonary, hepatic, renal, hematologic, endocrine, or other systemic diseases; patients with epilepsy or psychiatric disorders;
7. Received mesenchymal stem cell therapy within less than 3 months prior to screening;
8. Breastfeeding women, women planning to become pregnant during the study period, or men planning to father a child;
9. Significant laboratory abnormalities:

(1) Hemoglobin < 90 g/L in males, < 85 g/L in females; (2) White blood cell count < 3 × 10^9/L; (3) Platelet count < 90 × 10^9/L; (4) AST or ALT > twice the upper limit of normal; (5) Other laboratory results considered markedly abnormal by the investigator; 10.Presence of active infection, including acute, chronic, or local infections (e.g., sepsis, abscess, opportunistic infection, invasive fungal infection, etc.); 11.Oral antibiotic use within 2 weeks prior to screening, or intramuscular/intravenous antibiotic treatment for infection within 4 weeks prior to screening, or a history of severe infection within 6 months prior to screening (the investigator should assess the potential risk of enrollment based on individual clinical history); 12.History of recurrent herpes zoster, history of Listeria infection, history of reticuloendothelial fungal disease, or other chronic or recurrent infections; 13.Presence of one or more of the following conditions:

1. Inability to perform activities of daily living, requiring a wheelchair or bedridden due to limited mobility;
2. Severe cardiac, pulmonary, hepatic, or renal dysfunction;
3. Uncontrolled hypertension (150/100 mmHg);
4. History of congestive heart failure (New York Heart Association Class III/IV);
5. History of acute myocardial infarction or unstable angina within 12 months prior to screening;
6. Cerebrovascular or cardiovascular event within 3 months prior to dosing (myocardial infarction, ischemic or hemorrhagic stroke (excluding lacunar infarction), severe arrhythmia, deep vein thrombosis, etc.);
7. Any clinically significant respiratory disease, including but not limited to chronic obstructive pulmonary disease, asthma, interstitial pneumonia, bronchiectasis, pleural effusion;
8. History of demyelinating disease or clinical suspicion of such disease, including but not limited to multiple sclerosis, Guillain-Barré syndrome;
9. Unstable diabetes mellitus without stable dosing control within 4 weeks prior to screening (HbA1c < 6.5% at screening);
10. Other inflammatory arthritis or rheumatic diseases (other than AS) that may affect the evaluation of clinical efficacy, including but not limited to rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gouty arthritis;
11. Any neurological, psychiatric, or other systemic disease that may affect the evaluation of clinical efficacy;
12. History of malignancy within the past 5 years (excluding cured non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma, or cervical carcinoma in situ);
13. History of lymphoma or lymphoproliferative disease; 14.Concomitant use of the following medications:

(1) Use of glucocorticoids, except for oral prednisone at a daily dose ≤ 10 mg or equivalent dose of other corticosteroids, with the dose stable for at least 4 weeks; (2) Patients who discontinued leflunomide and received cholestyramine (8 g three times daily) for 2 weeks must have a 4-week washout period before screening. Patients who discontinued leflunomide without taking cholestyramine must have a 12-week washout period from the last dose of leflunomide to screening; (3) Use of alkylating agents within 12 months prior to screening; (4) Intra-articular, intramuscular, or intravenous injection of corticosteroids within 4 weeks prior to screening; 15.The investigator considers the patient unsuitable for enrollment in this trial.