Clinical trial NCT02809781: A Pilot Study of MSCs Iufusion and Etanercept to Treat Ankylosing Spondylitis
Official title: Phase III Study of Human Bone Marrow-Derived Mesenchymal Stem Cells to Treat AS
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Spondylitis
Spondylitis, Ankylosing
Ankylosis
Arthritis
Spondylarthritis
Spondylarthropathies
Spinal Diseases
Musculoskeletal Diseases
Bone Diseases
Keywords: ankylosing spondylitis
mesenchymal stem cell
etanercept
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Nanfang Hospital, Southern Medical University
name: Second Affiliated Hospital of Guangzhou Medical University
First posted: 2016-06-22
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and clinical effect of mesenchymal stem cells (MSCs) derived from human bone marrow at a dose of 1.0E+6 MSC/kg in subject for the therapy of Ankylosing spondylitis (AS) and to compare the efficacy of MSCs and Etanercept to treat this disease.

Detailed description: Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease involving primarily the sacroiliac joints and the axial skeleton. The main clinical features are back pain and progressive stiffness of the spine. Oligoarthritis of the hips and shoulders, enthesopathy, and anterior uveitis are common, and involvement of the heart and lungs is rare. The current understanding of the pathogenesis of this disorder is limited.It mainly about to hereditary susceptibility (eg HLA-B27),infection and autoimmunity.

Although traditional drugs, such as Nonsteroidal antiinflammatory drugs (NSAIDs) disease-modifying antirheumatic drugs (DMARDs such as methotrexate, salicylazosulfapyridine OR thalidomide) and steroids have been used in the treatment of AS, however, many studies have indicated that the overall response to these drugs is not satisfied. Addition, the severe side effects of these drugs have also been observed. The management of AS patients therefore remains unsatisfactory and targeted therapies are needed. Although the application of TNF alpha receptor inhibitor (such as Etanercept) has got the success in the early treatment of ankylosing spondylitis, the tolerance to this biological agent make the therapy to this disease rather difficult. Recently, owning to its immunoregulatory, immunosuppressive, stimulating hematopoiesis and tissue repairing properties, the infusion of human MSCs isolated from human bone marrow have been a promising and effective treatment to AS patients. This study will evaluate the safety and effectiveness of MSC transplantation in the AS patients and compare the efficiency with the Etanercept to treat AS patients.

This study will last 2 to 3 years. Participants will be randomly assigned to receive either MSC transplant therapy (experimental group) or Etanercept therapy (control group). Patients will undergo MSC transplant at the start of the study on Day 0. The experimental group will receive infusion per week in the first 4 weeks and every two weeks in the second 8 weeks, totally for 12 weeks. After 3 months, patients will receive the second MSC transplantation. After 12 weeks (Phase I) and 48 weeks (Phase II) from the first transplantation, patients will be evaluated.

Eligibility criteria: Inclusion Criteria:

1. The male or female patient aged 18 to 45 years;
2. Fulfill 1984 modified NewYork classification criteria for AS;
3. The score of the Bath AS Disease Activity Index (BASDAI)≥40 on (0-100) despite optimal non-steroidal anti-inflammatory drug (NSAID) treatment.
4. Before each experiment, patients subscribe voluntarily to the agreement approved by Ethics Committees and sign the date.

Exclusion Criteria:

1. The patient diagnosed in doubt;
2. Completely stiff spine
3. Received spinal or joint surgery within 2 months
4. Received anti-TNF therapy within 3 months
5. pregnant or suckling period female patients;
6. Patients with the Medical or mentally imbalance charged by researchers. patients associated cardiovascular, cerebrovascular, liver,renal and hematological system diseases or mental disease;
7. Patients could not accept the research or could not cooperate well. Patients with other sever diseases at the same time, such as abnormality of joints, other seronegative spondyloarthropathy, or other Rheumatic Diseases.

Primary outcomes:
measure: The Assessment of Spondyloarthritis International Society (ASAS)20 response
timeFrame: 48 weeks
Secondary outcomes:
measure: BASDAI score comparing to baseline
timeFrame: 48 weeks
measure: BASFI score comparing to baseline
timeFrame: 48 weeks
measure: Imageology
timeFrame: 48 weeks
measure: C-reactive protein (CRP)
timeFrame: 12 weeks
measure: Erythrocyte sedimentation rate (ESR)
timeFrame: 12 weeks
measure: Tumor necrosis factor alpha (TNF-α)
timeFrame: 12 weeks
measure: Interleukin 6 (IL-6)
timeFrame: 12 weeks
measure: Interleukin 17 (IL-17)
timeFrame: 12 weeks
Other outcomes:
measure: Percentage of systemic T cell population
timeFrame: 12 weeks
measure: Side effects
timeFrame: 48 weeks
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Shen Huiyong, Doctor
role: PRINCIPAL_INVESTIGATOR
References: