Mesenchymal Stem Cells Infusion in Patients With Autoimmune Diseases

Launched by NATIONAL INSTITUTE OF BLOOD AND MARROW TRANSPLANT (NIBMT), PAKISTAN · Mar 15, 2025

Keywords

ClinConnect Summary

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...

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Eligibility criteria

• Inclusion Criteria:
• • A- RA
• • 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
• Exclusion Criteria:
• • • 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 .
• • Primary or secondary immunodeficiency Inclusion criteria for ankylosing spondlitis Male or non-pregnant, non-lactating female patients at least 18 years of age
• Diagnosis of moderate to severe AS with prior documented radiologic evidence (x-ray or radiologist's report) fulfilling the Modified New York criteria for AS:
• • Active AS assessed by BASDAI ≥4 (0-10) at Baseline
• • Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at Baseline
• • Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at Baseline Patients should have had inadequate response or failure to respond to at least 2 NSAIDs at an approved dose for a minimum of 4 weeks in total and a minimum of 2 weeks for each NSAID prior to randomization, or less than 4 weeks if therapy had to be withdrawn due to intolerance, toxicity or contraindications Patients who are regularly taking NSAIDs (including COX-1 or COX-2 inhibitors) as part of their AS therapy are required to be on a stable dose for at least 2 weeks before randomization patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFα agent Exclusion criteria for ankylosing spondlitis
• • Chest X-ray or MRI with evidence of ongoing infectious or malignant process
• • Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
• • Pregnant or nursing (lactating) women Inclusion criteria for dermatomyositis
• • 5 to 50 Years of age
• • Adults with definite or probable dermatomyositis or polymyositis and pediatric patients five years of age and over with definite or probable juvenile dermatomyositis by Bohan and Peter criteria. Diagnosis of JDM based on an age of onset (i.e., first symptom of myositis or dermatomyositis rash) is less 16 years of age
• • Refractory myositis, defined by intolerance to or inadequate response to corticosteroids plus an adequate regime of at least one other immunosuppressive agent. Intolerance is defined as side effects that require discontinuation of the medication or an underlying condition that precludes further use of the medication.
• • Baseline manual muscle testing which is based on a maximum MMT-8 (Manual Muscle Test) score of 150:Adult subjects with dermatomyositis (DM) or polymyositis (PM) must have a score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.
• Subjects with a diagnosis of Juvenile Dermatomyositis (JDM) must meet either of the following criteria:
• • 1. An MMT-8 (Manual Muscle Test) score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.
• • OR
• • 2. If MMT (Manual Muscle Test) score is greater than 125/150 the patient MUST meet at least 3 abnormal core set measures.
• • Background therapy with at least 1 non-corticosteroid immunosuppressive agent at a stable dose for at least 6 weeks prior to screening
• • Able and willing to complete self-report questionnaires. Parents of pediatric participants will be required to complete the questionnaires on behalf of their children.
• • Willing to use acceptable forms of contraception for the duration of the study for patients of reproductive potential.
• • Parent willing to provide informed consent, if applicable
• • Willing to forgo immunization with a live vaccine for the duration of the study Exclusion for dermatomyositis
• • Drug-induced myositis. Patients who have myositis or myopathic syndromes caused by taking medications known to induce myositis-like syndromes, including but not limited to statin agents, fibric acid derivatives, colchicine, and hydroxychloroquine.
• • Inclusion body myositis
• • Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer. Patients with basal or squamous cell skin cancer or carcinoma in situ of the cervix are not excluded, if it has been at least 5 years since excision.
• • Myositis in overlap with another connective tissue disease that may preclude the accurate assessment of a treatment response
• • Live viral vaccine within 4 weeks prior to study entry
• • Any joint disease or other musculoskeletal condition that may interfere with muscle strength testing
• • Known hypersensitivity to mouse proteins
• • Any concomitant or life-threatening non-myositis illness that, in the opinion of the investigator, may interfere with the study
• • Known or suspected history of drug or alcohol abuse within the last 6 months prior to study entry, as determined by medical record or patient interview
• • Anticipated poor compliance with study requirements
• • Participation in another clinical trial within 30 days prior to screening
• • Any history or evidence of any severe illness or other condition that, in the opinion of the investigator, may interfere with the study
• • Previously received rituximab
• • Evidence of prior infection with hepatitis B or hepatitis C virus
• • Initiation of an exercise program within 4 weeks of screening OR initiation of an exercise program during the study
• • Consumed any creatine-containing, over-the-counter products in the form of dietary supplements 30 days prior to screening visit and for the duration of the study