Clinical Trial to Evaluate Efficacy and Safety of JOINTSTEM in Patients With Degenerative Arthritis

Multicenter, Randomized, Double-Blind, Placebo Controlled Phase Ⅱb Clinical Trial to Evaluate Efficacy and Safety of JOINTSTEM in Patients With Degenerative Arthritis

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

Study Overview

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

Detailed Description

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

It primarily aims to improve pain and joint function, and secondary, to regenerate cartilage. The intra-articular injection of JOINTSTEM is expected to stimulate the regeneration and growth of cartilage, and to innovatively improve pain and joint function with cartilage regeneration within six months.

The subjects of this therapy were regenerative patients with K&L grade 2~4 aged 18 or older. JOINTSTEM is expected to be used in patients who have significantly damage cartilage due to its cartilage regeneration ability, in addition to its improvement of pain and joint performance. A;sp. Patients who had already undergone knee arthroplasty can delay their additional surgery with the use of JOINTSTEM. For dose who still have their own cartilage, arthroplasty is not an immediate treatment option, and osteoporosis patients who cannot undergo arthroplasty due to their advanced age can receive JOINTSTEM.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-720
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 134-727
    • KyungHee University Gangdong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 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 osteoarthritis by ACR osteoarthritis of the knee
4. Diagnosis of osteoarthritis by radiographic criteria of Kellgren and Lawrence grade 2-4
5. More than Grade 4 (0~10 point numeric scale) pain at least for 12 weeks
6. Diagnosis of osteoarthritis of class Ⅰ~Ⅲ by ACR(American College of Rheumatology Criteria) Global functional criteria
7. Patient who agree with contraception

Exclusion Criteria:

1. Preparing for Pregnancy or Pregnant women or lactating mothers.
2. Patients with Body Mass Index (BMI) > 35.

3. Patients with other disease including

   : Septic arthritis, Rheumatoid or Inflammatory joint disease, Crystalline disease (gout or pseudogout), Paget disease, Articular fractures, Ochronosis, Acromegaly, Hemochromatosis, Wilson's disease, Osteochondromatosis, Hereditary disorder

4. Patients with serious condition internal medicine disease
5. Patients with positive human immunodeficiency (HIV), hepatitis B (HBV), hepatitis C (HCV), syphilis at screening indicative of current of pass infection.
6. Patient with behavioral disorders, cognitive disorders and chronic mental symptoms
7. Patient with significant neurologic or psychiatric disorders
8. Patients who alcohol, drug abuse history
9. Patients who had participated in other clinical trials within 12 weeks prior to this study.
10. Patients who received any drug by intra-articular injection for treatment within 2 months prior to this enrollment.
11. Patients who experienced as the knee joint cartilage and stem cell therapy
12. Patients who the principal investigator considers inappropriate for the clinical trial due to any other reasons than those listed above
13. Patients who penicillin hypersensitivity reactions -

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/3ml), 1 time injection; Other Names: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml
Placebo Comparator: Saline solution; Sodium chloride	Drug: Saline solution; Saline solution (Sodium chloride 9mg/ml), 1 time injection; Other Names: Sodium chloride 9mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC score	Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC 3 subscale	Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC)	24 weeks
KOOS (Knee Injury & Osteoarthritis Outcome Score)	Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS)	24 weeks
SF(Short Form)-36 Score	The SF(Short Form)-36 Health Survey is a 36-item, patient-reported survey of patient health.	24 weeks
Global assessment of disease activity	Change From Baseline in Patient's & Physician's Global Assessment of Disease Activity Score at 12,24 weeks by 100mm VAS(Visual Analogue Scale)	24 weeks
Overall satisfaction	Patient's overall satisfaction on a 0-100mm VAS(Visual Analogue Scale)	24 weeks
X-ray	X-ray perform to measure with Kellgren-Lawrence grade	24 weeks
MRI scan	MRI perform to measure cartilage defect size change from baseline up to 24weeks	24 weeks
Arthroscopy evaluation	Arthroscopy performs to evaluate any change in cartilage defect at the time of cell injection, and at 24 weeks after injection	24 weeks
Histological evaluation	Biopsy specimens subject to safranin-O staining and immunohistochemistry for type I and II collagen. Thickness of the articular cartilage before and after injection measure, and specimens evaluate with ICRS(International Cartilage Repair Society) II by a blind histopathologist.	24 weeks
VAS	Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)	24 weeks
IKDC	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)	24 weeks
ROM	change from baseline in knee flexion Range of Motion(ROM) at 12,24 weeks by physical examination	24 weeks
Quadriceps power	Change from baseline in quadriceps power at 12,24 weeks by physical examination	24 weeks
effusion	Change from baseline in 4-grade knee effusion at 12,24 weeks	24 weeks
Crepitus	Change from baseline in asymptomatic and symptomatic crepitus at 12,24 weeks by physical examination	24 weeks
Ligament laxity	Change from baseline in ligament laxity at 12,24 weeks by physical examination	24 weeks
Medial joint line tenderness	Change from baseline in 4-grade(none, mild, moderate, severe) medial joint line tenderness at 12,24 weeks by physical examination	24 weeks
Pes tenderness	Change from baseline in 4-grade(none, mild, moderate, severe) Pes tenderness at 12,24 weeks by physical examination	24 weeks

Collaborators and Investigators

• Sponsor: R-Bio

Publications and helpful links

General Publications

• Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. Stem Cells Transl Med. 2019 Jun;8(6):504-511. doi: 10.1002/sctm.18-0122. Epub 2019 Mar 5.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: August 3, 2015
• First Submitted That Met QC Criteria: January 14, 2016
• First Posted (Estimate): January 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 5, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: osteoarthritis; Stem cell; degenerative arthritis; biostar; Rbio; adipose tissue derived mesenchymal stem cell
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: Jointstem2b