Safety and Tolerance of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in Patients With Ankylosing Spondylitis

NCT05962762 | Not Yet Recruiting Phase 1

• 1 other identifier: QS-AS-S1
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses of human umbilical cord mesenchymal stem cell injection in patients with Ankylosing Spondylitis, and to further explore the efficacy, pharmacodynamic profile and appropriate dose of administration to provide a basis for the use of safer and more effective treatments for patients with Ankylosing Spondylitis in the future. Participants are required to sign an informed consent form and, after undergoing a series of tests and meeting the protocol's entry and exclusion criteria, are assigned to a dose group for intravenous infusion of human umbilical cord mesenchymal stem cells.

Conditions

Ankylosing Spondylitis

Keywords

Human umbilical cord mesenchymal stem cell; ankylosing spondylitis

Outcome Measures

Primary Outcomes (2)

• Adverse Event (AE)

  Incidence and severity of any adverse events related to the treatment of the trial drug that occurred during the clinical trial

  Through study completion, an average of 1 year

• Maximum tolerated dose (MTD)

  Explore the MTD after administration of the test drug

  Through study completion, an average of 1 year

Secondary Outcomes (12)

• Improvement of Assessment in ankylosingspondylitis 20 (ASAS20)

  Baseline, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

• Improvement of Assessment in ankylosingspondylitis 50 (ASAS50)

  Baseline, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

• Change of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

  Baseline, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

• Change of Bath Ankylosing Spondylitis Functional Index (BASFI)

  Baseline, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

• Change of Bath Ankylosing Spondylitis Metrology Index (BASMI)

  Baseline, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

Other Outcomes (20)

• Interleukin-2 (IL-2)

  Baseline, Day 2, Day 3, Day 7, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

• Interleukin-6 (IL-6)

  Baseline, Day 2, Day 3, Day 7, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

• Interleukin-17 (IL-17)

  Baseline, Day 2, Day 3, Day 7, Day 14, Day 28, Week 12, Week 24, Week 36, Week 48

Study Arms (1)

Human Umbilical Cord Mesenchymal Stem Cell Injection

EXPERIMENTAL

The trial was divided into three dose groups： Low-dose group: 1000000 cells/kg Medium-dose group: 3000000 cells/kg High-does group: 5000000 cells/kg

Biological: Human Umbilical Cord Mesenchymal Stem Cells

Interventions

Human Umbilical Cord Mesenchymal Stem Cells BIOLOGICAL

The trial was conducted sequentially from the low dose group to the high dose group, with 3-6 subjects enrolled in each dose group. The trial was conducted on a case-by-case basis in the high dose group, with each subject in the high dose group being enrolled in subsequent subjects only after completion of at least 7 days of post-dose safety observation. Each subject received only one corresponding dose. All subjects received experimental drugs and conventional treatment during the study period. All subjects in each test dose group will complete a 4-week (28-day) dose-limiting toxicity (DLT) After the observational evaluation period, a decision will be made by the investigator and sponsor based on a discussion of relevant safety data whether to start the next dose group.

Human Umbilical Cord Mesenchymal Stem Cell Injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A definitive diagnosis of ankylosing spondylitis (AS) (according to the 1984 New York Revised Criteria, Annex 1) with active AS. Active AS is defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4. Active AS is defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4;
• Received at least 2 non-steroidal anti-inflammatory drugs (NSAIDs) for a total of 4 weeks or more prior to screening. Patients who received at least 2 NSAIDs for a total of 4 weeks or more without significant improvement in symptoms as evaluated by the investigator or who were intolerant; if Patients receiving salazosulfapyridine and/or methotrexate should have been on treatment for at least 3 months or longer and on a stable dose for at least 4 weeks or more prior to enrollment. If the patient is receiving salazosulfapyridine and/or methotrexate, the length of treatment prior to enrollment should be at least 3 months and longer and the stable dose at least 4 weeks and longer;
• If the patient is receiving glucocorticosteroid therapy, stabilization for at least 4 weeks prior to enrollment to a dose equivalent to ≤ 10 mg of prednisone/day;
• Patients and spouses who do not plan to have children within 1 week prior to screening and within 6 months after the end of the trial and who agree to to use effective non-pharmacological contraception during the trial;
• Patients voluntarily signed an informed consent form and were willing to cooperate with the trial process.
• Note: CT findings may be accepted if the diagnosis is not clear on x-ray.

You may not qualify if:

• Those with complete spinal rigidity;
• Those with hypersensitivity to known components of the test drug, or a history of severe allergy.
• Persons with a history of any malignancy (except basal cell carcinoma of the skin, carcinoma in situ) within 5 years prior to dosing
• Persons with a cardiovascular or cerebrovascular event (heart attack, ischemic or hemorrhagic stroke (except lacunar cerebral infarction), severe cardiac arrhythmia, deep vein thrombosis, etc.) within 3 months prior to dosing
• Those who have had a serious infection or have an active infection requiring intravenous antibiotic treatment within 4 weeks prior to screening
• Lactating females or females with positive blood pregnancy test results at screening/baseline
• Persons with known human immunodeficiency virus infection or impaired immune function or infectious disease (e.g. HBsAg positive, HBcAb positive with HBV-DNA titer \> 1000 IU/ml, HCV-Ab, HIV-Ab, syphilis test (TRUST), tuberculosis test (T-SPOT.TB) positive);
• Patients who have participated in other clinical trials or studies within 2 months prior to dosing;
• Those who have been treated with TNF-alpha antagonists or other biological agents within 3 months prior to dosing
• Those who have received DMARDs class drugs within 1 month prior to dosing (except for those treated with salazosulfapyridine or methotrexate for 3 months or more prior to screening and at a stable dose for at least 4 weeks or more) with leflunomide discontinuation \<8 weeks; or those with discontinuation time \<7 drug half-lives depending on the actual drug class (i.e. DMARDs class drug elution period should exceed 7 half-lives of the corresponding drug), whichever is longer;
• Those whose screening or baseline phase examination meets any of the following: Glutamic aminotransferase (AST) or glutamic alanine aminotransferase (ALT) \> 2.5 x ULN (non-hepatic source excluded); Serum creatinine \> 1.5 x ULN or glomerular filtration rate a \< 60 mL/min/1.73 m2; Activated partial thromboplastin time (APTT) \>1.5×ULN or prothrombin time (PT) \> 2.5 x ULN (not receiving anticoagulation); Left ventricular ejection fraction ≤ 45%.
• Previously treated with stem cell therapy;
• Subjects with any other irreversible condition or symptom with an expected survival of \<3 months
• Those who have undergone spinal or joint surgery within 2 months prior to dosing;
• History of alcoholism, mental illness, drug abuse, or use of any drug within 12 months prior to administration;

Sponsors & Collaborators

• Asia Cell Therapeutics (Shanghai) Co., Ltd.: lead
• RenJi Hospital: collaborator

MeSH Terms

Conditions

Spondylitis, Ankylosing

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Study Officials

• Chunde Bao

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenli Liu

CONTACT

+86 13402137712; liuwenli@xibaozhiliao.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: July 27, 2023
• Study Start: August 30, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 15, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share