Ankylosing Spondylitis
Conditions
Brief summary
The goal of this clinical trial is to learn if allogeneic human bone marrow-derived mesenchymal stem cells (CG-BM1) are safe and show preliminary efficacy in treating patients with ankylosing spondylitis (AS). It will also explore the appropriate dose of CG-BM1. The main questions it aims to answer are: What medical problems (adverse events) do participants have when taking CG-BM1? (Safety and tolerability) Does CG-BM1 improve disease activity, pain, and function in patients with AS? (Preliminary efficacy) Researchers will compare CG-BM1 to a placebo (an inactive substance that looks like CG-BM1) in the second phase of the study to see if CG-BM1 works for AS. This study has two phases: Phase 1 (dose-escalation): Open-label, single-arm. Participants will receive one of three escalating doses of CG-BM1 weekly for 4 weeks. Phase 2 (dose-expansion): Randomized, double-blind, placebo-controlled. Participants will receive either the recommended dose of CG-BM1 or a placebo weekly for 4 weeks, in addition to standard background therapy (celecoxib). Participants will: Receive CG-BM1 or placebo via intravenous infusion once a week for 4 weeks Visit the clinic for follow-up assessments at Week 1, 4, 8, 12, and 24 after the first infusion Undergo physical exams, laboratory tests (blood and urine), and complete questionnaires about disease activity, pain, and function (e.g., BASDAI, VAS, ASAS response criteria)
Interventions
BIOLOGICALIV administration of CG-BM1
Dose level 1: CG-BM1 1.0×10⁶ cells/kg, IV, weekly × 4 + celecoxib, 0.2g, p.o. daily Dose level 2: CG-BM1 2.0×10⁶ cells/kg, IV, weekly × 4 + celecoxib, 0.2g, p.o. daily Dose level 3: CG-BM1 4.0×10⁶ cells/kg, IV, weekly × 4 + celecoxib, 0.2g, p.o. daily
BIOLOGICALPlacebo
Sodium Chloride Solution, 5 ml, IV, weekly × 4+ celecoxib, 0.2g, p.o. daily
BIOLOGICALCG-BM1
CG-BM1 \[recommended dose\], IV, weekly × 4 + celecoxib, 0.2g, p.o. daily
Sponsors
Eighth Affiliated Hospital, Sun Yat-sen University
Guangzhou Cellgenes Biotechnology Co.,Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Meet the diagnostic criteria for ankylosing spondylitis (AS) * Age 18 to 40 years * Must be able to understand and communicate with the investigator, comply with study requirements, and provide signed and dated informed consent before any study assessments are performed * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) total score ≥ 4 (0-10 scale), and total back pain measured by VAS ≥ 40 mm (0-100 mm) * CRP or ESR elevated ≥ 1.5 times the upper limit of normal * Patients taking methotrexate (≤ 25 mg/week) or sulfasalazine (≤ 3 g/day) are permitted to continue these medications, provided they have been used for at least 3 months and maintained at a stable dose for at least 4 weeks prior to randomization. Patients taking methotrexate must maintain stable folic acid supplementation prior to randomization * Patients taking DMARDs other than methotrexate and sulfasalazine must discontinue them at least 4 weeks prior to randomization * No prior use of any form of biologics within 6 months * Spinal X-ray must rule out complete rigid ankylosis
Exclusion criteria
* Known allergy to any component of the study drug (primarily bone marrow mesenchymal stem cells; excipients include dimethyl sulfoxide, human albumin, etc.) * Current evidence of infection or malignancy as shown by chest X-ray or MRI within 3 months prior to screening * Currently using potent opioid analgesics * Received any intra-articular injection therapy (e.g., corticosteroids) within 4 weeks prior to randomization * Received any intramuscular corticosteroid injection within 2 weeks prior to randomization * Received traditional Chinese medicine treatment for AS within 4 weeks prior to randomization * Pregnant or breastfeeding women * Presence of underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious, or gastrointestinal disease that, in the investigator's opinion, would place the patient at unacceptable risk if treated with immunomodulatory agents * Significant health problem or disease including (but not limited to): uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure, uncontrolled diabetes, or extremely poor functional status rendering the patient unable to care for themselves * History of renal impairment, glomerulonephritis, or a single kidney, or serum creatinine level \> 1.5 mg/dL * Active systemic infection within 2 weeks prior to randomization (common cold excluded) * Current infection or history of chronic, recurrent infectious disease, or clinical test suggesting tuberculosis (including latent tuberculosis) * Known HIV infection, hepatitis B, or hepatitis C at screening or randomization * History or evidence of alcohol or drug abuse within 6 months prior to randomization * History of lymphoproliferative disease or known malignancy of any organ system within the past 5 years * Pulmonary arterial hypertension class III or IV (WHO functional classification) at screening * History of deep vein thrombosis at screening, or history of pulmonary embolism within 3 months prior to screening * Any other condition that, in the investigator's opinion, makes the patient unsuitable for participation in the study (e.g., lack of compliance, difficulty in long-term follow-up)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | 24 weeks |
| Incidence of Dose-Limiting Toxicities (DLTs) | 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ASAS20 Response | Weeks 1, 4, 8, 12, and 24 | ASAS20 response is defined as an improvement of \> 20% and an absolute improvement of \> 1 unit (on a 0-10 scale) or \> 10 mm (on a 0-100 mm scale) in at least 3 of the following 4 domains: Patient Global Assessment, Physical Function (BASFI), Total Spinal Pain, and Inflammation (Morning Stiffness). Additionally, there must be no worsening in the remaining domain. |
| Global Assessment of Disease Activity | Weeks 1, 4, 8, 12, and 24 | Evaluated using a 0-10 Visual Analog Scale (VAS), where 0 indicates "not active" and 10 indicates "very active". Higher scores represent greater disease activity. The outcome will report the change from baseline values at each subsequent visit timepoint. |
| Total Spinal Pain Intensity Score | Weeks 1, 4, 8, 12, and 24 | Measured by a Visual Analog Scale (VAS) ranging from 0 mm (no pain) to 100 mm (severe pain), calculating the average score of overall spinal pain and nocturnal spinal pain over the past week. Higher scores represent worse pain intensity. |
| Bath Ankylosing Spondylitis Functional Index (BASFI) | Weeks 1, 4, 8, 12, and 24 | BASFI consists of 10 items assessing the patient's ability to perform specific activities of daily living. Each item is scored on a 0-10 scale (0 = easy, 10 = impossible). The total score is calculated as the mean of the 10 scores, where a higher score indicates more severe functional impairment. |
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | Weeks 1, 4, 8, 12, and 24 | BASDAI evaluates 6 items: fatigue, spine pain, peripheral joint pain, localized tenderness, morning stiffness severity, and morning stiffness duration over the past week, each on a 0-10 scale. The final score is calculated as the average of the first 4 items plus the average of the two morning stiffness items, with a total range of 0 to 10. Higher scores indicate more severe disease activity. |
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | Weeks 1, 4, 8, 12, and 24 | BASMI evaluates spinal mobility based on 5 clinical measurements: cervical rotation, tragus-to-wall distance, lumbar flexion (modified Schober's test), lumbar side flexion, and intermalleolar distance. Each component is scored linearly from 0 to 2, with a total composite score ranging from 0 to 10. Higher scores indicate more severe impairment of spinal mobility. |
| Swollen Joint Count(SJC) and Tender Joint Count(TJC) Based on 44-Joint Assessment | Weeks 1, 4, 8, 12, and 24 | Peripheral arthritis progression will be evaluated via the standard 44-joint count assessment. Scores range from 0 to 44 joints, where a reduction in count indicates therapeutic improvement. |
| Serum C-reactive Protein (CRP) Concentration (mg/L) | Weeks 1, 4, 8, 12, and 24 | Evaluated via peripheral blood samples to explore the systemic anti-inflammatory effect of CG-BM1. |
| Erythrocyte Sedimentation Rate (ESR) (mm/h) | Weeks 1, 4, 8, 12, and 24 | Evaluated via peripheral blood samples to explore the systemic anti-inflammatory effect of CG-BM1. |
| Serum Concentrations of Cytokines (TNF-α and BMP2) (pg/mL) | Weeks 1, 4, 8, 12, and 24 | Measured via enzyme-linked immunosorbent assay (ELISA) from collected serum samples to investigate the mechanistic pathways of bone remodeling and immune regulation. |
| Peripheral Blood Immune Cell Subset Percentages | Weeks 1, 4, 8, 12, and 24 | Evaluated via multicolour flow cytometry to quantify the percentages of CD4+ T cells, CD8+ T cells, Treg cells, Th17 cells, NK cells, MAIT cells, monocytes, neutrophils, and B cells relative to total lymphocytes or leukocytes, in order to track immune homeostasis reconstruction. |
Countries
China
Contacts
CONTACTProf.Wang
Outcome results
None listed