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

Sponsor

R-Bio (Industry)

Overall Status

Completed

CT.gov ID

NCT03990805

Collaborator

(none)

260

Enrollment

Locations

Arms

18.2

Actual Duration (Months)

21.7

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Degenerative Arthritis Knee Osteoarthritis	Biological: JOINTSTEM Drug: saline	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

260 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 11, 2019

Actual Primary Completion Date :

Dec 15, 2020

Actual Study Completion Date :

Dec 15, 2020

Arms and Interventions

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 saline	Drug: saline saline, 1 time injection

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

saline

Drug: saline

saline, 1 time injection

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

WOMAC 3 subscale score [12 weeks, 24 weeks]
Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC)
VAS score [12 weeks, 24 weeks]
Pain of knee will be measured by the 100mm Visual Analog Scale (VAS)
KOOS [12 weeks, 24 weeks]
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)
SF-36 [12 weeks, 24 weeks]
The SF(Short Form)-36 Health Survey is a 36-item, patient-reported survey of patient health.
IKDC [12weeks, 24 weeks]
Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)
Measuring of Kellgren-Lawrence grade [12 weeks, 24 weeks]
Measuring of Kellgren-Lawrence grade through X-ray
Measuring of Femoro-tibial anatomical angle(FTA) [12 weeks, 24 weeks]
Measuring of FTA through X-ray
Measuring of Hip-Knee-Ankle angle(HKA) [12 weeks, 24 weeks]
Measureing of HKA through X-ray
Measuring of Joint Space Width [12 weeks, 24 weeks]
measuring Joint Space Width through X-ray
MRI scan [12 weeks, 24 weeks]
MRI perform to measure Modified WORMS (Whole-Organ Magnetic Resonance Imaging Score)
Use of rescue medication [12 weeks, 24 weeks]
Frequency and total amount of rescue medication administration will be measured.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Patients who has joint pain ≥ 50mm on 100mm VAS (Visual Analog Scale) at Screening
Patient who has WOMAC score ≥ 1000 at Screening
No improvement with persisting knee pain at least for 12 weeks (3 months) by nonoperational therapy before Screening

Exclusion Criteria:

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

Pregnant women or lactating mothers
Patients with Body Mass Index (BMI) > 35
Patients with positive human immunodeficiency (HIV), hepatitis B (HBV), hepatitis C (HCV), syphilis at screening indicative of current of pass infection
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

Patients who are diagnosed with malignant tumor in the past or present
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.)

Patients who have significant lab abnormalities
Patients who have severe pain in other areas that can affect the judgement of knee joint symptom
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
Patients who received any drug by intra-articular injection(hyaluronic acid or steroid etc.) for treatment within 6 months prior to Screening
Patients who experienced as stem cell therapy or blood product injection(PRP, Prolo injection etc.)
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.)

Patients with penicillin hypersensitivity reactions
Patients with skin diseases or infections in the area of the injection site
Patients who have abnormal flail over grade 2 flail knee test of anterior to posterior and varus/valgus lesion at physical examination
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
Patients who have difficulty in liposuction or local anesthesia
Patients who have alcohol, drug abuse history
Patients who have severe neurologic and psychiatric disorders that affect clinical trials
Patients who had participated in other clinical trials within 12 weeks prior to this study
Patients who the principal investigator considers inappropriate for the clinical trial due to any other reasons than those listed above

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Chungbuk National University Hospital	Cheongju-si	Korea, Republic of	28644
2	Yeungnam University Hospital	Daegu	Korea, Republic of	42415
3	Keimyung University Dongsan Medical Center	Daegu	Korea, Republic of	42601
4	Chonbuk National University Hospital	Jeonju	Korea, Republic of	54907
5	Gyeongsang National University Hospital	Jinju-si	Korea, Republic of	52727
6	Kyunghee University Medical Center	Seoul	Korea, Republic of	02447
7	Yonsei University Health System	Seoul	Korea, Republic of	03722
8	Soonchunhyang University Hospital Seoul	Seoul	Korea, Republic of	04401
9	KyungHee University Gangdong Hospital	Seoul	Korea, Republic of	05278
10	Gangnam Severance Hospital	Seoul	Korea, Republic of	06273
11	Samsung Medical Center	Seoul	Korea, Republic of	06351
12	Chunang University Hospital	Seoul	Korea, Republic of	06973