Safety and Efficacy of Allogeneic Bone Marrow MSCs in Ankylosing Spondylitis

Official title

An Early Exploratory Clinical Study on the Safety and Preliminary Efficacy of Allogeneic Human Bone Marrow Mesenchymal Stem Cells in Patients With Ankylosing Spondylitis

Overview

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

• Biological IV 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
• Biological Placebo
  Sodium Chloride Solution, 5 ml, IV, weekly × 4+ celecoxib, 0.2g, p.o. daily
• Biological CG-BM1
  CG-BM1 \[recommended dose\], IV, weekly × 4 + celecoxib, 0.2g, p.o. daily

Primary outcome measures

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: 24 weeks]
• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: 24 weeks]

Secondary outcome measures (11)

• Percentage of Participants Achieving ASAS20 Response [Time frame: Weeks 1, 4, 8, 12, and 24]
• Global Assessment of Disease Activity [Time frame: Weeks 1, 4, 8, 12, and 24]
• Total Spinal Pain Intensity Score [Time frame: Weeks 1, 4, 8, 12, and 24]
• Bath Ankylosing Spondylitis Functional Index (BASFI) [Time frame: Weeks 1, 4, 8, 12, and 24]
• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [Time frame: Weeks 1, 4, 8, 12, and 24]
• Bath Ankylosing Spondylitis Metrology Index (BASMI) [Time frame: Weeks 1, 4, 8, 12, and 24]
• Swollen Joint Count(SJC) and Tender Joint Count(TJC) Based on 44-Joint Assessment [Time frame: Weeks 1, 4, 8, 12, and 24]
• Serum C-reactive Protein (CRP) Concentration (mg/L) [Time frame: Weeks 1, 4, 8, 12, and 24]
• Erythrocyte Sedimentation Rate (ESR) (mm/h) [Time frame: Weeks 1, 4, 8, 12, and 24]
• Serum Concentrations of Cytokines (TNF-α and BMP2) (pg/mL) [Time frame: Weeks 1, 4, 8, 12, and 24]
• Peripheral Blood Immune Cell Subset Percentages [Time frame: Weeks 1, 4, 8, 12, and 24]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Eighth Affiliated Hospital, Sun Yat-sen University — Shenzhen

Identifiers

NCT: NCT07632599 · MR-44-26-023756

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗