Mesenchymal Stem Cells Infusion in Patients With Autoimmune Diseases - A Phase II Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Primary Outcome Measures for RA
研究概览
简要总结
The goal of this study is to learn if mesenchymal stem cell therapy (treatment group) can effectively treat autoimmune diseases, when compared to normal saline (given to placebo group). The primary outcome measures will be clinical improvement based on the respective disease specific clinical scores, normalization of T-lymphocyte subsets and > 50% reduction in disease specific antibody titres. The study will also document the type and frequency of any adverse event or side effects, reported by or seen in any of the trial participants.
Patients in treatment group will receive single session of MSC therapy and placebo group will receive 0.9% saline solution. The participants will be followed at 3 and 6 months.
详细描述
The autoimmune disorders are a spectrum of diseases ranging from organ-specific, in which antibodies and T cells react to self-antigens localized in a specific tissue, to systemic, which are characterized by reactivity against a specific antigen(s) spread throughout various tissues in the body. The incidence of different autoimmune diseases is variable, according to the Centers for Disease Control and Prevention, 22.7% have rheumatic diseases. Although no population-based epidemiological study has been carried out in Pakistan purely on autoimmune diseases; a study by Mohsin Z et al. reports the combined prevalence of rheumatic diseases at a tertiary hospital in Karachi to be 17.3%. Autoimmune diseases and their treatment modalities are the prime cause of disability in developing countries and have the highest incapacitating rates in health-related quality of life (HRQoL) and daily functioning.
The 21st century has seen rapid advances in the treatment of diseases of immune dysfunction. One such treatment modality is stem cell therapy which is believed to repair and regenerate tissues. In particular, mesenchymal stem cells (MSCs) have been applied to treat diseases associated with age, changing lifestyle, immune dysfunction and stroke. MSC therapy has promise to treat various autoimmune disorders like refractory systemic lupus erythematosus (SLE), Crohn's disease, systemic sclerosis (SS), rheumatoid arthritis (RA), multiple sclerosis (MS), graft versus host disease, diabetes mellitus, thyroiditis and even different types of neurological disorders. At present, nearly a thousand clinical trials have used MSC-based therapies. Among those around one hundred trials have been conducted for treatment of immune-mediated disorders, the first one being more than fifteen years ago (table 1).
The interest surrounding field of MSCs was initially based on their inherent capacity for self-renewal and regeneration with a potential to form cells of mesodermal origin (adipocytes, osteocytes, chondrocytes, hepatocytes, neurons, muscle cells and epithelial cells) depending on the surrounding microenvironment. Later on, due to their abilities to home to inflamed areas and exert immunomodulatory effects, therapies with MSCs extended to treatment of autoimmune and chronic inflammatory processes. Multiple studies have also demonstrated that MSCs have intrinsic immunomodulatory and anti-inflammatory properties.
Table 1: Clinical trials in which mesenchymal stem cells are being used as therapeutic modality.
Immune mediated disorder Number of Clinical trials Year of first Clinical trial Reference Graft vs. host disease 49 2004 Inflammatory bowel disease 23 2006 Multiple sclerosis 29 2006 Systemic lupus erythematosus 10 2007 Type I diabetes 26 2008 Primary Sjögren syndrome 1 2009 Type II diabetes 13 2010 Autoimmune hepatitis 2 2011 Ankylosing spondylitis 2 2011 Chronic urticarial 1 2017 Refractory autoimmune thrombocytopenia 1 2019
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 Years and older
- •Diagnosis of RA, as defined by fulfilling 2010 American College of Rheumatology (ACR) criteria
- •Positive for rheumatoid factor (RF) and/or anticyclic citrullinated peptide (CCP)
- •The presence of arthritis symptoms for more than 6 weeks but less than 5 year
- •Active RA, as defined as DAS ESR>3.1 (as defined by moderate and sever RA )
- •Willing to adhere to the study requirements
- •Willing to use acceptable effective forms of contraception
排除标准
- •• Allergy to methotrexate (MTX)
- •Previous exposure to anti-CD20 monoclonal antibody (mAb) or other type(s) of mAb therapy
- •Receipt of intra-articular injections within 4 weeks prior to study entry
- •Unwilling to stop drinking alcohol (ETOH)
- •History of alcohol or substance abuse
- •Active infection, or chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., Human Immunodeficiency Virus [HIV], hepatitis B virus [HBV], hepatitis C virus [HCV], tuberculosis [TB])
- •Interstitial lung disease observed by chest x-ray [chest radiograph]
- •Known coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure (New York Heart Association [NYHA] classes III or IV)
- •Definitive diagnosis of another autoimmune rheumatologic disease (e.g., systemic lupus erythematosus [SLE], scleroderma, primary Sjögren's syndrome, primary vasculitis)
- •History of immunoglobulin E (IgE)-mediated or non-IgE-mediated hypersensitivity or known anaphylaxis to mouse proteins
- •History of cancer. Exception: participants with previous resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ Grade I cervical cancer within 5 years prior to study entry are not excluded from study eligibility
- •History of positive purified protein derivative (PPD) test (i.e., positive tuberculosis [TB] test or mantoux test) without treatment for TB infection or chemoprophylaxis for TB exposure
- •Live vaccine within 3 months of study entry
- •Any psychiatric disorder that would prevent a participant from providing informed consent
- •Pregnancy or breastfeeding women.
- •HIV-positive patients.
- •Patients receiving any other investigational/disease modifying agents within 4 weeks of study entry.
- •History of allergic reactions attributed to compounds of similar biologic composition to mesenchymal stem cells.
- •Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent and perform all study assessments.
- •Active Malignancy
- •Any other serious medical illness that might preclude safe participation in the study.
- •Inclusion criteria for SLE
- •Adults aged at least 18 years old
- •Active musculoskeletal SLE diagnosed by SLICC criteria.
- •No contraindication to the use of IV methylprednisolone, biosimilar rituximab, or any other required medications such as antipyretics and antihistamines
- •Willing to use appropriate contraception if at risk of pregnancy
- •Disease activity that is refractory to hydroxychoroquine and one DMARD, or patients unable to take hydroxychoroquine due to contra-indication or prior toxicity Exclusion criteria for SLE Severe "critical" SLE flare defined as: (i) BILAG 2004 A flare in CNS system; (ii) BILAG 2004 A flare in the renal system; or (iii) any other SLE manifestation requiring more immunosuppression than allowed within the protocol in the physician's opinion
- •Pregnancy
- •Breast Feeding
- •Malignancy
- •Receipt of intravenous immunoglobulin, plasma exchange or cyclophosphamide within the last 3 months
- •Rituximab within the past 18 months or other biologic therapies within the past 6 months
- •Active infections, including but not limited to the human immunodeficiency virus, hepatitis B (including prior infection as judged by positive Hepatitis B core antibody) or hepatitis C
- •Receipt of a live attenuated vaccine within 3 months prior to study enrolment
- •History of cancer in the past 5 years except for squamous or basal cell carcinoma that has been completely excised or treated cervical carcinoma in situ
- •Planned surgery within the study period that is expected to require overnight hospital admission
- •Any other concomitant medical condition that, in the investigator's opinion, or after discussion with the CI, places the participant at risk by participating in this study Inclusion criteria for systemic sclerosis
- •Adult patients, >/= 18 years of age
- •Systemic sclerosis, as defined by American College of Rheumatology (1980) criteria
- •Disease duration upto 5 years (defined as time from first non-Raynaud phenomenon manifestation)
- •>/= 15 and </= 40 mRSS units at screening
- •Active disease, as defined by protocol
- •Negative pregnancy test for a female subject of childbearing potential Exclusion criteria
- •Major surgery (including joint surgery) within 8 weeks prior to and/or during study enrollment
- •Rheumatic autoimmune disease other than systemic sclerosis
- •Previous treatment with tocilizumab
- •History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- •Severe cardiopulmonary disease
- •Known active current or history of recurrent infections
- •Use of any investigational, biologic, or immunosuppressive therapies .
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研究组 & 干预措施
Treatment group
MSC therapy group
干预措施: Mesenchymal Stem Cells (Biological)
Placebo group
Placebo (0.9% saline)
干预措施: Placebo (Other)
结局指标
主要结局
Primary Outcome Measures for RA
时间窗: Day 0, Weeks 12, 24, 48
Change From Baseline in Physician's Global Assessment of Patient's Disease Activity- Visual Analog Scale (PhGADA-VAS) at Week 48
Primary Outcome Measures for Systemic lupus erythematosus
时间窗: Day 0, Weeks 12, 24, 48
Proportion of patients achieving BILAG-based Composite Lupus Assessment (BICLA)
Primary Outcome Measures for systemic sclerosis
时间窗: Day 0, Weeks 12, 24, 48
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Primary outcome measures in ankylosing spondlitis
时间窗: Week 16
The Proportion of Participants Who Achieve an ASAS 20 Response (Assessment of SpondyloArthritis International Society Criteria) ASAS20 response is defined as an improvement of ≥20% and ≥1 units on a scale of 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the remaining domain
Primary Outcome Measure for dermatomyositis
时间窗: Day 0, Weeks 12, 24, 48
Comparison Between the Time to Improvement Between the Two Groups of Idiopathic Inflammatory Myopathy Patients at week 48 ASAS20 response is defined as an improvement of ≥20% and ≥1 units on a scale of 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the remaining domain
次要结局
- Secondary Outcome Measures for RA(Day 0, Week 12, week 24, week48)
- Secondary Outcome Measures for SLE(Day 0, Weeks 12, 24, 48)
- Secondary Outcome Measures for SC(Day 0, Weeks 12, 24, 48)
- Secondary Outcome Measure for ALS(Week 16)
- Secondary Outcome Measure for ankylosing spondlitis(Week 16)
- Secondary Outcome Measure for dermatomyositis(Day 0, Weeks 12, 24, 48)