A Phase 3 Study to Evaluate the Efficacy and Safety of JointStem in Treatment of Osteoarthritis

Multi-center, Randomized, Double-Blind, Placebo Controlled Phase 3 Clinical Trial to Evaluate Efficacy and Safty of Mesenchymal Stem Cells JointStem in Patients With Knee Osteoarthritis

The purpose of this study is to investigate the efficacy and safety of autologous Adipose Tissue derived Mesenchymal stem cells (JOINTSTEM®) in patient with severe Knee Osteoarthritis.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Degenerative Arthritis
• Intervention / Treatment: Biological: JOINTSTEM; Drug: saline

Detailed Description

JOINTSTEM is injectables for an OA treatment that uses autologous adipose-derived mesenchymal stem cells. As it does not use allogenic tissues and is cultured without additional genetic modification, it is classified as 'autologous cell therapy' and is completely free of immunologic rejection.

It primarily aims to improve joint function. The intra-articular injection of JOINTSTEM is expected to stimulate the regeneration of cartilage, and to innovatively improve joint function with cartilage regeneration.

The subjects of this therapy were patients with K&L grade 3 aged 20 or older.

This study is a double-blind, randomized, placebo controlled study with two arms to evaluate JOINTSTEM as a treatment for subjects with osteoarthritis. Following a 2-week screening period, approximately 260 patients will be randomly assigned into one of the following two arms in a 1:1 ratio (1 JointStem : 1 placebo control). After each patient completes 6-month visit (Visit 5) and the data management team confirms all data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Cheongju-si, Korea, Republic of, 28644
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Hospital
  • Daegu, Korea, Republic of, 42601
    • Keimyung University Dongsan Medical Center
  • Jeonju, Korea, Republic of, 54907
    • Chonbuk National University Hospital
  • Jinju-si, Korea, Republic of, 52727
    • Gyeongsang National University Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 02447
    • Kyunghee University Medical Center
  • Seoul, Korea, Republic of, 03722
    • Yonsei University Health System
  • Seoul, Korea, Republic of, 05278
    • KyungHee University Gangdong Hospital
  • Seoul, Korea, Republic of, 06591
    • Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 06973
    • Chunang University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 20 and older, male and female
2. Patients must consent in writing to participate in the study by signing and dating an informed consent document
3. Diagnosis of degenerative arthritis of class 1-3 by ACR(American College of Rheumatology Criteria) Global functional criteria
4. Diagnosis of Kellgren and Lawrence grade 3 by radiographic criteria

5. Patients suitable for one of three conditions of 'diagnostic criteria for osteoarthritis of knee' based on ACR guideline

   • clinical and inspectional opinion
   • clinical and radiographic opinion
   • clinical opinion
6. Patients who has joint pain ≥ 50mm on 100mm VAS (Visual Analog Scale) at Screening
7. Patient who has WOMAC score ≥ 1000 at Screening
8. No improvement with persisting knee pain at least for 12 weeks (3 months) by nonoperational therapy before Screening

Exclusion Criteria:

1. Patients who have pregnancy plans within this trial period or childbearing age patients who do not agree to maintain contraception status through appropriate contraception methods

   • Appropriate contraception method: Use of condom, contraceptive sponges, foam, diaphragm, intrauterine device etc.
   • Periodic abstinence(e.g. methods of predicting ovulation) and moderation are not considered as appropriate contraception method.
   • Not allowed to use hormonal contraceptives
   • Childbearing age female patients, exclude menopausal female (amenorrhea for more than 24 months after the last menstruation) or female who has no possibility of pregnency by surgical sterilization operation, can participate in this study only determined negative in pregnancy test
2. Pregnant women or lactating mothers
3. Patients with Body Mass Index (BMI) > 35
4. Patients with positive human immunodeficiency (HIV), hepatitis B (HBV), hepatitis C (HCV), syphilis at screening indicative of current of pass infection

5. Patients with other disease including

   • Septic arthritis, Rheumatoid or Inflammatory joint disease, Gout, Reccurent pseudogout, Paget disease, Articular fractures, Ochronosis, Acromegaly, Hemochromatosis, Wilson's disease,Osteochondromatosis, Hereditary disorder, Genetic disorder of collagen
6. Patients who are diagnosed with malignant tumor in the past or present

7. Patients who have clinically significant diseases including

   • Cardiac disorder (Myocardial infarction, Coronary artery bypass graft, Arrhythmia and other severe Cardiac disorder etc.)
   • Resistant hypertension (systolic blood pressure > 160mmHg or diastolic pressure > 100mmHg at Screening)
   • Kidney disease (Chronic renal failure, Glomerulonephritis etc.)
   • Liver disease (Hepatocirrhosis, Fatty liver, acute or chronic liver disease etc.)
   • Endocrinopathy (Thyroiditis, Diabetes insipidus, Cushing disease etc.)
8. Patients who have significant lab abnormalities
9. Patients who have severe pain in other areas that can affect the judgement of knee joint symptom
10. Patients who underwent any arthroscopic surgery on the injection site within 6 months of the screening visit date, or scheduled to perform any surgery during the clinical trial period
11. Patients who received any drug by intra-articular injection(hyaluronic acid or steroid etc.) for treatment within 6 months prior to Screening
12. Patients who experienced as stem cell therapy or blood product injection(PRP, Prolo injection etc.)

13. Patients who received treatment within 14 days prior to Screening including(But, patients who had wash-out-period can participate in this study)

    • Take medicines including composition of Glucosamine, Chondretin sulphate and Diacerhein etc.
    • Take phytotherapeutic agent or Chinese medicine for osteoarthritis
    • Take antiinflammatory analgesic drug, NSAIDs (prescription/nonprescription pharmaceuticals) etc. (Patients who have 3 days of wash-out-period after they took acetaminophen can participate in the study)
    • Take oral steroids
    • Physical therapy or Chinese medical treatment(cupping, acupuncture, moxibustion etc.)
14. Patients with penicillin hypersensitivity reactions
15. Patients with skin diseases or infections in the area of the injection site
16. Patients who have abnormal flail over grade 2 flail knee test of anterior to posterior and varus/valgus lesion at physical examination
17. Patients who have difficulty in taking MRI because of metal materials (cardiac pacemaker or clip of cerebral artery etc.) in their body or claustrophobia -but, patients with metal materials that are not affected by magnetic field can participate in this study
18. Patients who have difficulty in liposuction or local anesthesia
19. Patients who have alcohol, drug abuse history
20. Patients who have severe neurologic and psychiatric disorders that affect clinical trials
21. Patients who had participated in other clinical trials within 12 weeks prior to this study
22. Patients who the principal investigator considers inappropriate for the clinical trial due to any other reasons than those listed above

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JOINTSTEM; Autologous Adipose Tissue derived MSCs	Biological: JOINTSTEM; JOINTSTEM Autologous Adipose Tissue derived MSCs 1x10^8cells/(saline), 1 time injection; Other Names: Autologous Adipose Tissue derived MSCs
Placebo Comparator: saline	Drug: saline; saline, 1 time injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) scores from baseline	Pain, stiffness, and physical function of the knee will be measured by the WOMAC score; Score range is0-20 for Pain0-8 for Stiffness0-68 for Pysical Function; Higher scores on the WOMAC indicate wors pain, stiffness, and functional limitations	12 weeks, 24 weeks
Change of Visual Analog Scale (VAS) scores from baseline	Pain of knee will be measured by the 100mm VAS -Score range is from 0-4mm(no pain) to 75-100mm(severe pain)	12 weeks, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC 3 subscale score	Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC)	12 weeks, 24 weeks
VAS score	Pain of knee will be measured by the 100mm Visual Analog Scale (VAS)	12 weeks, 24 weeks
KOOS	Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS) -Score range is from 0(extreme symptoms) to 100(no symptoms)	12 weeks, 24 weeks
SF-36	The SF(Short Form)-36 Health Survey is a 36-item, patient-reported survey of patient health.	12 weeks, 24 weeks
IKDC	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)	12weeks, 24 weeks
Measuring of Kellgren-Lawrence grade	Measuring of Kellgren-Lawrence grade through X-ray	12 weeks, 24 weeks
Measuring of Femoro-tibial anatomical angle(FTA)	Measuring of FTA through X-ray	12 weeks, 24 weeks
Measuring of Hip-Knee-Ankle angle(HKA)	Measureing of HKA through X-ray	12 weeks, 24 weeks
Measuring of Joint Space Width	measuring Joint Space Width through X-ray	12 weeks, 24 weeks
MRI scan	MRI perform to measure Modified WORMS (Whole-Organ Magnetic Resonance Imaging Score)	12 weeks, 24 weeks
Use of rescue medication	Frequency and total amount of rescue medication administration will be measured.	12 weeks, 24 weeks

Collaborators and Investigators

• Sponsor: R-Bio
• Investigators: Principal Investigator: KangIl Kim, M.D., Ph.D., KyungHee University Gangdong Hospital; Principal Investigator: WOOSUK LEE, M.D., Ph.D., Gangnam Severance Hospital; Principal Investigator: SUNCHUL HWANG, M.D., Ph.D., Gyeongsang National University Hospital; Principal Investigator: SANGJUN SONG, M.D., Ph.D., Kyunghee University Medical Center; Principal Investigator: KICHEOR BAE, M.D., Ph.D., Keimyung University Dongsan Medical Center; Principal Investigator: YOUNGWAN MOON, M.D., Ph.D., Samsung Medical Center; Principal Investigator: JUHONG LEE, M.D., Ph.D., Chonbuk National University Hospital; Principal Investigator: HANJUN LEE, M.D., Ph.D., Chunang University Hospital; Principal Investigator: EUISUNG CHOI, M.D., Ph.D., Chungbuk National University Hospital; Principal Investigator: YONG IN, M.D., Ph.D., Seoul St. Mary's Hospital; Principal Investigator: KWANKYU PARK, M.D., Ph.D., Yonsei University; Principal Investigator: OOGJIN SHON, M.D., Ph.D., Yeungnam University Hospital; Principal Investigator: MYUNGCHUL LEE, M.D., Ph.D., Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2019
• Primary Completion (Actual): December 15, 2020
• Study Completion (Actual): December 15, 2020

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: osteoarthritis; Stem Cell; degenerative arthritis; Adipose tissue derived mesenchymal stem cell; biostar; Rbio
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: BSR-CTph3-JS1

Drug and device information, study documents

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