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

Ankylosing Spondylitis Clinical Trial

Official title: A Clinical Trial to Evaluate the Safety, Tolerance and Efficacy of aCell Injection of Allogeneic UC-MSCs in Patients With Ankylosing Spondylitis

Status Not yet recruiting

Clinical Trial 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.

Clinical Trial Description

Ankylosing spondylitis (AS) is an inflammatory disease of unknown origin that mainly affects the sacroiliac joints, spinal prominences, paraspinal soft tissues and peripheral joints, and may be accompanied by extra-articular manifestations, and in severe cases, spinal deformities and ankylosis. The etiology of AS is still unclear, but epidemiology shows a strong association with genetic and environmental factors. Treatment is aimed at relieving signs and symptoms, restoring physical function, preventing joint damage, improving quality of life, and preventing complications of spinal disorders. Treatment methods include patient education such as physical exercise and proper posture in life and sleep; pharmacological treatment such as non-steroidal anti-inflammatory drugs (NSAIDs), biologics (e.g. TNF-α antagonists, IL-17 antagonists), DMARDs (e.g. salbutamol, methotrexate), glucocorticoids, etc. In addition, surgical methods such as total hip arthroplasty are also available. Despite these therapeutic or disease control methods, none of them can stop the radiological progression of AS, restore the structural damage of patients, or achieve a cure for the disease.

Stem cells are undifferentiated cells that exist in embryonic or adult tissues and have the potential for self-renewal replication and multidirectional differentiation. Mesenchymal stem cells (MSCs) are one of the most used stem cells in basic and clinical research. According to the literature, MSCs have the ability to migrate and nest in diseased and damaged tissues in vivo, and repair damaged tissues through their multidirectional differentiation potential. MSCs can also improve the local microenvironment, support and promote the regeneration and differentiation of endogenous stem cells, exert anti-inflammatory effects and regulate immunity through their paracrine mechanisms. The collection of human umbilical cord derived mesenchymal stem cells (hUC-MSCs) is non-invasive and there are no medical ethics issues in obtaining them.

There are no medical ethics issues in obtaining them. Similar to other tissue-derived MSCs, hUC-MSCs have a unique self-renewal capacity and multidirectional differentiation potential, such as the ability to differentiate into adipose, bone, cartilage, nerve and liver cells [6]. These properties make hUC-MSCs have the theoretical possibility to treat AS.

Currently, studies on MSCs for the treatment of ankylosing spondylitis (AS) are in the exploratory stage, and several studies have confirmed the safety and efficacy of MSCs for the treatment of AS.

The primary objective of this clinical trial was to examine the safety and tolerability of human umbilical cord MSC injection in patients with AS, and the secondary objective was to examine the initial effectiveness of human umbilical cord MSC injection in treating patients with AS. The trial was designed as a single-arm, single-dose, dose-escalation clinical trial with three dose groups: low-dose group (1,000,000 cells/kg), medium-dose group (3,000,000 cells/kg), and high-dose group (5,000,000 cells/kg). A "3+3" dose escalation design was used, with 3-6 subjects included in each dose group, sequentially from the low to the high dose group. Each subject in the high-dose group was enrolled on a case-by-case basis, and each subject in the high-dose group was allowed to enroll in subsequent subjects only after completing at least 7 days of safety observation after dosing. Each subject received only one corresponding dose.

After all subjects in each trial dose group have completed a 4-week (28-day) dose-limiting toxicity (DLT) observation period, the decision to start the next dose group will be made by the investigator and sponsor after discussion of relevant safety data. Subjects will enter the follow-up period after completing the D28 visit, and the investigator will continue to observe the safety and efficacy of the subjects after dosing.

The investigators continued to monitor the safety and efficacy of the drug after administration. If a subject experiences disease progressiona or requires other treatment (including but not limited to biologics), the investigator will determine whether the subject should be discontinued from the patient risk-benefit perspective and discharged from the group as specified; subjects discharged from the group as determined by the investigator will be followed up as specified for long-term follow-up.

Subjects who have completed the DLT observation period in the previous dose group and have confirmed that the drug is safely tolerated, the investigator and sponsor will agree on whether to proceed to the next dose group. Concurrent enrollment in 2 or more dose groups is not permitted. If during the trial a dose group is observed to meet the termination dose creep criteria, the dose escalation will be terminated and a decision to continue the study with a downward dose adjustment will be made by the investigator and sponsor. The previous dose in the dose group that reached the termination criteria was designated as the maximum tolerated dose (MTD). If the MTD has not been explored and the subject is still safely tolerated after completion of the highest dose group (5,000,000 cells/kg) preset for this trial, the decision to continue with a higher dose escalation will be made by the investigator in consultation with the sponsor.

The extent of adverse events observed in the trial will be determined by the CTCAE 5.0 grading scale, with the following The dose creep will be terminated and the investigator and sponsor will mutually agree whether to use the previous dose as the MTD for the single dose tolerance trial. MTD of the dosing tolerance test.

1. 1 DLT in 3 subjects in a dose group; 3 additional subjects will be included in that dose group for tolerance testing;

2. If ≥2 DLTs occur in 6 subjects in a dose group, the previous dose level of that dose level defined as MTD and dose escalation was stopped.

If the maximum dose group is reached and still no MTD is defined, the investigator and sponsor consult to determine if continued creep. ;

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

• NCT number: NCT05962762
• Study type: Interventional
• Source: Asia Cell Therapeutics (Shanghai) Co., Ltd.
• Contact: Wenli Liu
• Phone: +86 13402137712
• Email: liuwenli@xibaozhiliao.cn
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 30, 2023
• Completion date: December 31, 2027