Safety and Efficacy of Allogeneic Bone Marrow MSCs in Ankylosing Spondylitis

Официальное название

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

Обзор

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)

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (11)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT07632599 · MR-44-26-023756

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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