- ICH GCP
- USA klinikai vizsgálatok nyilvántartása
- Klinikai vizsgálat NCT07632599
Safety and Efficacy of Allogeneic Bone Marrow MSCs in Ankylosing Spondylitis
An Early Exploratory Clinical Study on the Safety and Preliminary Efficacy of Allogeneic Human Bone Marrow Mesenchymal Stem Cells in Patients With Ankylosing Spondylitis
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)
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- 1. fázis
Kapcsolatok és helyek
Tanulmányi kapcsolat
- Név: Prof.Wang
- Telefonszám: 86+138 2602 4785
- E-mail: wangp57@mail.sysu.edu.cn
Tanulmányi helyek
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Guangdong
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Shenzhen, Guangdong, Kína, 518033
- The Eighth Affiliated Hospital, Sun Yat-sen University
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Kapcsolatba lépni:
- Prof. Chen
- Telefonszám: 86+83982222
- E-mail: sysuehoffice@mail.sysu.edu.cn
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
- Felnőtt
Egészséges önkénteseket fogad
Leírás
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)
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Szekvenciális hozzárendelés
- Maszkolás: Kettős
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
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Kísérleti: phase 1:CG-BM1 Dose Escalation Cohorts
Participants will be sequentially assigned to one of three dose cohorts using a "3+3" design: low-dose (1*10^6 cells/kg), medium-dose (2.0*10^6 cells/kg), or high-dose 4.0*10^6 cells/kg).
In each cohort, CG-BM1 will be administered via intravenous infusion once weekly for a total of 4 doses on Days 0, 7, 14, and 21.
All participants across all cohorts will concurrently receive standard background therapy consisting of celecoxib 0.2g orally once daily.
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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
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Placebo Comparator: phase 2 :placebo Cohorts
Participants will be randomized to receive the placebo (Compound Electrolyte Injection) via intravenous (IV) infusion once weekly for a total of 4 doses, mimicking the regimen of the experimental group.
All participants will simultaneously receive a background therapy of celecoxib 0.2g orally once daily.
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Sodium Chloride Solution, 5 ml, IV, weekly × 4+ celecoxib, 0.2g, p.o. daily
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Kísérleti: phase 2 :CG-BM1 Cohorts
Participants will be randomized to receive CG-BM1 at the clinically recommended dose (determined by the Safety Review Committee based on Phase 1 results) via intravenous (IV) infusion once weekly for a total of 4 doses.
All participants will simultaneously receive a background therapy of celecoxib 0.2g orally once daily.
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CG-BM1 [recommended dose], IV, weekly × 4 + celecoxib, 0.2g, p.o. daily
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Időkeret |
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Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Időkeret: 24 weeks
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24 weeks
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Incidence of Dose-Limiting Toxicities (DLTs)
Időkeret: 24 weeks
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24 weeks
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
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Percentage of Participants Achieving ASAS20 Response
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Global Assessment of Disease Activity
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Total Spinal Pain Intensity Score
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Bath Ankylosing Spondylitis Functional Index (BASFI)
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Bath Ankylosing Spondylitis Metrology Index (BASMI)
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Swollen Joint Count(SJC) and Tender Joint Count(TJC) Based on 44-Joint Assessment
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Serum C-reactive Protein (CRP) Concentration (mg/L)
Időkeret: Weeks 1, 4, 8, 12, and 24
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Evaluated via peripheral blood samples to explore the systemic anti-inflammatory effect of CG-BM1.
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Weeks 1, 4, 8, 12, and 24
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Erythrocyte Sedimentation Rate (ESR) (mm/h)
Időkeret: Weeks 1, 4, 8, 12, and 24
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Evaluated via peripheral blood samples to explore the systemic anti-inflammatory effect of CG-BM1.
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Weeks 1, 4, 8, 12, and 24
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Serum Concentrations of Cytokines (TNF-α and BMP2) (pg/mL)
Időkeret: Weeks 1, 4, 8, 12, and 24
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Measured via enzyme-linked immunosorbent assay (ELISA) from collected serum samples to investigate the mechanistic pathways of bone remodeling and immune regulation.
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Weeks 1, 4, 8, 12, and 24
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Peripheral Blood Immune Cell Subset Percentages
Időkeret: Weeks 1, 4, 8, 12, and 24
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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.
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Weeks 1, 4, 8, 12, and 24
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Együttműködők és nyomozók
Együttműködők
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- MR-44-26-023756
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
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