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

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: FURESTEM-RA Inj; Other: sterile saline

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gwangju, Korea, Republic of
    • Chonnam National University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of
    • Gangdong Kyung Hee University Hospital
  • Seoul, Korea, Republic of
    • Seoul Hospital attached to Soonchunhyang University
  • Seoul, Korea, Republic of
    • Seoul national University Boramae

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. of either gender, 19-80years old
2. Subjects must be diagnosed according to the 2010 ACR/EULAR criteria for at least 12 weeks duration.
3. Subjects must be diagnosed with ACR functional class I. II, III
4. ≥ 6 tender joints, swollen joints (68 joint count) at Screening
5. Subject who has moderate to severe disease activity (DAS28-ESR>3.2) on screening visit

6. 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.

   1. people that have no effect with permitted dose taking for more than 3 months
   2. people with a history of side effects of relevant treatment
7. 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
8. 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
9. In case of taking NASAIDs, Tramadol patients with stable amount of medication at least 2 weeks before screening visit.
10. During screening visit , patients with an ESR result of 28mm/hr; patients with a 1.0mg/dL or greater in a CRP testing
11. Subject who understands and voluntarily sign an informed consent form

Exclusion Criteria:

1. Subjects who is diagnosed ACR function class IV Rheumatoid Arthritis
2. 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
3. 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.)

4. 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
5. Subject who has history of hypersensitivity, heavy metal poisoning, etc. to drugs which is composed of similar components.
6. 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
7. Subject who has administered ACTH(adrenocorticotropic hormone) agents within 4 weeks before screening visit
8. Subject who has undergone administration of any investigational drug within 30 days before screening visit.
9. Use of prohibited medication or inability to avoid the use of prohibited medication during the study
10. Pregnant, breast-feeding women
11. A female or male in their childbearing ages that is not willing to take proper contraceptive methods during a study
12. Subject who has sever dyshepatia (Serum creatinine level ≥ 1.7mg/dl)
13. Subject who has severe renal dysfunction (ALT/AST/bilirubin value ≥ 2 upper limit of the normal range at screening test)
14. Any other condition which the PI Judges would make patient unsuitable for study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FURESTEM-RA Inj.	Biological: FURESTEM-RA Inj; 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
PLACEBO_COMPARATOR: Placebo Comparator: Placebo	Other: sterile saline; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kang Stem Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 11, 2018
• Primary Completion (ACTUAL): October 5, 2021
• Study Completion (ACTUAL): May 13, 2022

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: August 6, 2018
• First Posted (ACTUAL): August 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Cell therapy; FURESTEM-RA Inj.
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: K0202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No