Safety and Efficacy of FURESTEM-RA Inj. in Patients With Moderate to Severe Rheumatoid Arthritis

Study Overview
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Brief Summary
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Safety and Efficacy of FURESTEM-RA Inj. in Patients With Moderate to Severe Rheumatoid arthritis

Detailed Description
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Phase 1: Single center, open Phase 2a : Multi-center, randomized, double-blind, parallel, placebo Clinical Trial to Evaluate the Efficacy and Safety of FURESTEM-RA Inj. for Moderate to Severe Rheumatoid arthritis

Official Title
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A Multi-center, Randomized, Double-blind, Parallel, Placebo-controlled Phase I/2a Clinical Trial to Evaluate the Efficacy and Safety of FURESTEM-RA Inj. for Moderate to Severe Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: FURESTEM-RA Inj
* Other: sterile saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: of either gender, 19-80years old Subjects must be diagnosed according to the 2010 ACR/EULAR criteria for at least 12 weeks duration. Subjects must be diagnosed with ACR functional class I. II, III ≥ 6 tender joints, swollen joints (68 joint count) at Screening Subject who has moderate to severe disease activity (DAS28-ESR>3.2) on screening visit History of treatment for one of conventional DMARDs or biologic DMARDs or JAK inhibitors AND people diagnosed with either (a) or (b) by a trained person, or people that have potential side effects thus not qualified from using biologic DMARDs. people that have no effect with permitted dose taking for more than 3 months people with a history of side effects of relevant treatment Subjects must be taking cDMARDs(including methotrexate, sulfasalazine, hydroxychloroquine, leflunomide) or tacrolimus of stable dose More than 12 weeks before baseline visit and be willing to remain on stable dose throughout the study If subject is currently administering steroids everyday, when steroid dose is converted into prednisolone oral dose, the subject should take a stable dose(≤10mg/day) over 4 weeks on screening visit In case of taking NASAIDs, Tramadol patients with stable amount of medication at least 2 weeks before screening visit. During screening visit , patients with an ESR result of 28mm/hr; patients with a 1.0mg/dL or greater in a CRP testing Subject who understands and voluntarily sign an informed consent form Exclusion Criteria: Subjects who is diagnosed ACR function class IV Rheumatoid Arthritis Patients who are judged by the PI(or Sub-I) to be unable to participate in clinical trials due to uncontrolled or unstable cardiovascular disease or severe blood disease Subjects who has AIDS, other rheumatic disease(Crohn's disease, systemic lupus erythematosus, lyme disease, psoriatic arthritis, spondylarthropathy, infectious or reactive arthritis, reiter's syndrome, etc.) Prior use of bDMARDs, within the following windows prior to baseline 24 weeks for Rituximab 10 weeks for Abatacept, Golimumab, Certolizumab pegol, Tocilizumab 7 weeks for Infliximab 4 weeks for Etanercept 3 weeks for Tofacitinib, Baricitinib Subject who has history of hypersensitivity, heavy metal poisoning, etc. to drugs which is composed of similar components. Subject who has treated intravenous, intramuscular steroid injection within 2 weeks before screening visit or intra-articular steroid injection within 4 weeks before screening visit Subject who has administered ACTH(adrenocorticotropic hormone) agents within 4 weeks before screening visit Subject who has undergone administration of any investigational drug within 30 days before screening visit. Use of prohibited medication or inability to avoid the use of prohibited medication during the study Pregnant, breast-feeding women A female or male in their childbearing ages that is not willing to take proper contraceptive methods during a study Subject who has sever dyshepatia (Serum creatinine level ≥ 1.7mg/dl) Subject who has severe renal dysfunction (ALT/AST/bilirubin value ≥ 2 upper limit of the normal range at screening test) Any other condition which the PI Judges would make patient unsuitable for study participation

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FURESTEM-RA Inj.<br> | Biological: FURESTEM-RA Inj<br>* The allogeneic umbilical cord blood-derived mesenchymal stem cells of each dose level as below were mixed into an IV bag containing 100 ml of sterile saline solution and the IV bag was gently massaged to obtain homogeneous mixture of the cell suspension. Administer the constituted cell suspension by IV infusion to a subject. The infusion should be completed in 60 minutes using infusion pump. Dose level 1: 5.0 x 10^7 cells /body 3 repeated intravenous injection at 4 week intervals Dose level 2: 1.0 x 10^8 cells /body 3 repeated intravenous injection at 4 week intervals<br>|
| Placebo Comparator: Placebo Comparator: Placebo<br> | Other: sterile saline<br>* sterile saline 3 repeated intravenous injection at 4 week intervals Placebo were mixed into an IV bag containing 100 ml of sterile saline solution and the IV bag was gently massaged to obtain homogeneous mixture of the cell suspension. Administer the constituted cell suspension by IV infusion to a subject. The infusion should be completed in 60 minutes using infusion pump.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of FURESTEM-RA Inj. - number of adverse events | Evaluate the number of adverse events Safety of FURESTEM-RA Inj. | 4 weeks follow-up after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as measured by ACR(American College of Rheumatology)20,50,70 reaction rate |  | 16 weeks follow-up after treatment | 
| Efficacy as measured by EULAR (European League Against Rheumatism)reaction rate |  | 16 weeks follow-up after treatment | 
| Efficacy as measured by DAS(Disease activity scores)28-ESR | DAS range is from ≥ 3.2 (inactive) , >3.2 but ≤ 5.1(moderate), >5.1(very active) | 16 weeks follow-up after treatment | 
| Efficacy as measured by KHAQ(Korean Health assessment questionnaire) | KHAQ range is from 0 (clear) to 60 (severe) | 16 weeks follow-up after treatment | 
| Efficacy as measured by CDAI (clinical disease activity index) | CDAI range is from 0 (clear) to 76 (severe) | 16 weeks follow-up after treatment | 
| Efficacy as measured by 100mm Pain VAS(Visual analogue scale) | 100mm Pain VAS range is from 0 (clear) to 100 (severe) | 16 weeks follow-up after treatment | 
| Total number of use and consumed amount of rescue medicine |  | 16 weeks follow-up after treatment | 
| Change in Cytokine(TNF-a, Interleukin (IL)-1b, IL-4,IL-6,IL-8,IL-10,IL-13,IL-17A,IL-21,IL-22) |  | 16 weeks follow-up after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FURESTEM-RA Inj., Rheumatoid Arthritis, Cell therapy