SpondylitisPhase 2/3NCT02809781
A Pilot Study of MSCs Iufusion and Etanercept to Treat Ankylosing Spondylitis
A Phase 2/3 study testing Intravenous infusion of MSCs and Etanercept in people with Spondylitis and Spondylitis, Ankylosing, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Spondylitis, Spondylitis, Ankylosing, Ankylosis
- What is being tested?
- Intravenous infusion of MSCs and Etanercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteChina
- Study dates
- Jun 2016to Dec 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- The male or female patient aged 18 to 45 years;
- Fulfill 1984 modified NewYork classification criteria for AS;
- The score of the Bath AS Disease Activity Index (BASDAI)≥40 on (0-100) despite optimal non-steroidal anti-inflammatory drug (NSAID) treatment.
- Before each experiment, patients subscribe voluntarily to the agreement approved by Ethics Committees and sign the date.
Who cannot join
- The patient diagnosed in doubt;
- Completely stiff spine
- Received spinal or joint surgery within 2 months
- Received anti-TNF therapy within 3 months
- pregnant or suckling period female patients;
- Patients with the Medical or mentally imbalance charged by researchers. patients associated cardiovascular, cerebrovascular, liver,renal and hematological system diseases or mental disease;
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510120
Shen Huiyong, Doctor, +8602081332612, shenhuiyong@aliyun.com
About this study
Official title: Phase III Study of Human Bone Marrow-Derived Mesenchymal Stem Cells to Treat AS
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.
Read the 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.
- Conditions
- Spondylitis, Spondylitis, Ankylosing, Ankylosis, Arthritis, Spondylarthritis, Spondylarthropathies
- Being tested
- Intravenous infusion of MSCs, Etanercept
- Keywords
- ankylosing spondylitis, mesenchymal stem cell, etanercept
- Medical subject headings
- Spondylitis, Spondylitis, Ankylosing, Ankylosis, Arthritis, Spondylarthritis, Spondylarthropathies, Spinal Diseases, Musculoskeletal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous infusion of MSCsBiological
Intravenous infusion of MSCs:Human bone marrow-derived MSCs 1.0E+6 MSC/kg, IV drop
EtanerceptDrug
Also called TNF alpha receptor inhibitor
50mg,hypodermic injection,once per week, for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Intravenous infusion of MSCs | Experimental | Human bone marrow-derived MSCs at a dose of 1.0E+6 MSC/kg, receive infusion per week in the first 4 weeks and every two weeks in the second 8 weeks. total for 12 weeks. Receives: Biological: Intravenous infusion of MSCs |
| Etanercept | Active comparator | 50mg,hypodermic injection,once per week, for 12 weeks Receives: Drug: Etanercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Assessment of Spondyloarthritis International Society (ASAS)20 response
ASAS measures symptomatic improvement in AS patients.ASAS=4 domains:patient global assessment of disease activity,pain,function,inflammation.ASAS 20=20% improvement(vs.baseline)and an absolute change≥1 units on a 0-10 scale(0=no disease activity;10=high disease activity)for ≥3 domains,and no worsening in remaining domain.
Measured: 48 weeks
Secondary outcomes (8)
BASDAI score comparing to baseline
Measured: 48 weeks
BASFI score comparing to baseline
the Bath Ankylosing Spondylitis Functional Index
Measured: 48 weeks
Imageology
The bone marrow of the whole spine (from C2 to S1) can be detected by Magnetic resonance imaging (MRI) scan. The MRI sequence included a T1-weighted turbo spin-echo (TSE) sequence and a fat-saturated short tau inversion recovery (STIR) sequence.
MR images were first analyzed using the ASspiMRI-a scoring system , which is based on grading disease activity on a scale of 0 to 6. In addition to the ASspiMRI-a scoring system, the inflammation area and average intensityof each inflammatory site were calculated. The background value (BV) was obtained by taking 10 normal sites of the vertebral body of 1 layer and calculating the average. The inflammation extent of each inflammatory site was calculated by the formula:
value of inflammation area (VIA) × [value of average intensity (VAI) - BV]. The summation of the inflammation extent of all inflammatory sites in all scanning layers was defined as the total inflammation extent (TIE) of each patient.
Measured: 48 weeks
C-reactive protein (CRP)
Measured: 12 weeks
Erythrocyte sedimentation rate (ESR)
Measured: 12 weeks
Tumor necrosis factor alpha (TNF-α)
Measured: 12 weeks
Interleukin 6 (IL-6)
Measured: 12 weeks
Interleukin 17 (IL-17)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionAug 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SpondylitisStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Nanfang Hospital, Southern Medical University, Second Affiliated Hospital of Guangzhou Medical University
- Responsible party
- Principal investigator, Shen Huiyong, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Investigators
- Shen Huiyong, Doctor, Principal investigator, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02809781
- Sponsor's protocol ID
- SYSU-81332612
- Status last verified
- Jun 2016
- First submitted
- 16 Jun 2016
- Last updated
- 24 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: It all depends on the whole process of the study.
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Human Bone Marrow-Derived Mesenchymal Stem Cells to Treat AS
- ClinicalTrials.gov ID
- NCT02809781
- Acronym / sponsor ID
- SYSU-81332612
- Conditions
- Spondylitis, Spondylitis, Ankylosing, Ankylosis, Arthritis, Spondylarthritis, Spondylarthropathies
- Keywords
- ankylosing spondylitis, mesenchymal stem cell, etanercept
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Collaborators
- Nanfang Hospital, Southern Medical University, Second Affiliated Hospital of Guangzhou Medical University
- Study start
- Jun 2016
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 22 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous infusion of MSCs | Experimental | Biological: Intravenous infusion of MSCsHuman bone marrow-derived MSCs at a dose of 1.0E+6 MSC/kg, receive infusion per week in the first 4 weeks and every two weeks in the second 8 weeks. total for 12 weeks. |
| Etanercept | Active comparator | Drug: Etanercept50mg,hypodermic injection,once per week, for 12 weeks |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- The male or female patient aged 18 to 45 years;
- Fulfill 1984 modified NewYork classification criteria for AS;
- The score of the Bath AS Disease Activity Index (BASDAI)≥40 on (0-100) despite optimal non-steroidal anti-inflammatory drug (NSAID) treatment.
- Before each experiment, patients subscribe voluntarily to the agreement approved by Ethics Committees and sign the date.
Key exclusion criteria (7 listed)
- The patient diagnosed in doubt;
- Completely stiff spine
- Received spinal or joint surgery within 2 months
- Received anti-TNF therapy within 3 months
- pregnant or suckling period female patients;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous infusion of MSCsIntravenous infusion of MSCs:Human bone marrow-derived MSCs 1.0E+6 MSC/kg, IV drop | Biological | Intravenous infusion of MSCs |
| EtanerceptAlso: TNF alpha receptor inhibitor50mg,hypodermic injection,once per week, for 12 weeks | Drug | Etanercept |
Primary outcome
The Assessment of Spondyloarthritis International Society (ASAS)20 response
Time frame: 48 weeks
ASAS measures symptomatic improvement in AS patients.ASAS=4 domains:patient global assessment of disease activity,pain,function,inflammation.ASAS 20=20% improvement(vs.baseline)and an absolute change≥1 units on a 0-10 scale(0=no disease activity;10=high disease activity)for ≥3 domains,and no worsening in remaining domain.
8 secondary outcomes
BASDAI score comparing to baseline
Time frame: 48 weeks
BASFI score comparing to baseline
Time frame: 48 weeks
Imageology
Time frame: 48 weeks
C-reactive protein (CRP)
Time frame: 12 weeks
Erythrocyte sedimentation rate (ESR)
Time frame: 12 weeks
Tumor necrosis factor alpha (TNF-α)
Time frame: 12 weeks
Interleukin 6 (IL-6)
Time frame: 12 weeks
Interleukin 17 (IL-17)
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2016.
- Individual participant dataSharing planned: Undecided. It all depends on the whole process of the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shen Huiyong, Doctor principal investigator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Intravenous infusion of MSCs and Etanercept in people with Spondylitis and Spondylitis, Ankylosing, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shen Huiyong, Doctor (+8602081332612, shenhuiyong@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Assessment of Spondyloarthritis International Society (ASAS)20 response (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2016.