Investigator Initiated Trial to Evaluate the Efficacy and Safety of Intra-articular Injection of ADMSC Comared to Negative Control After High Tibial Osteotomy in the Osteoarthritis Patients.

Single-center, Randomized, Open Label, Negative-controlled Investigator Initiated Trial to Evaluate the Efficacy and Safety of Intra-articular Injection of ADMSC(Autologous Adipose Tissue Derived Mesenchymal Stem Cells) After High Tibial Osteotomy Compared to Negative Control in the Osteoarthritis Patients.

The purpose of this study is to evaluate the efficacy and safety of intra-articular injection of autologous adipose tissue derived mesenchymal stem cells compared after high tibial osteotomy to negative control in the osteoarthritis patients

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Degenerative Arthritis
• Intervention / Treatment: Biological: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml

Detailed Description

In this clinical trial, the investigational product is administered intra-articularly at 1 week after high tibial osteotomy in a patient with degenerative arthritis of the medial side.

The investigational product is autologous adipose-derived mesenchymal stem cells. As it does not use allogenic tissue 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 regenerate cartilage, to improve pain and joint function. The intra-articular injection of the investigational product is expected to stimulate the regeneration and growth of cartilage, and to innovatively improve pain and joint function with cartilage regeneration compared to high tibial osteotomy alone.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 134-727
    • KyungHee University Gangdong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must consent in writing to participate in the study by signing and dating an informed consent document
2. Patients who can communicate (exclusion of anyone who cannot understand the questionnaire)
3. between 20 years and 80 years of age
4. BMI≤30
5. Diagnosis of osteoarthritis by radiographic criteria of Kellgren and Lawrence grade 2-4
6. Diagnosis of osteoarthritis by ACR(American College of Rheumatology Criteria) Global functional criteria : There is the pain of the knee and radiographic osteophyte and at least one of the following (1) age >50 years (2) Less than 30 minutes of morning stiffness (3) The friction When moving weighted the knee
7. Patients who agree with contraception
8. Patients who agree to stop the existing osteoarthritis treatment and to get enough washout periods until medication time
9. Patients scheduled for High tibial osteotomy due to medial gonarthrosis

Exclusion Criteria:

1. patients with osteoporosis
2. Preparing for Pregnancy or Pregnant women or lactating mothers.
3. Patients with positive human immunodeficiency (HIV), hepatitis B (HBV), hepatitis C (HCV), venereal disease research laboratory(VDRL)
4. Patients with hypersensitivity to investigator product or investigational product component or those with a history
5. Patients who had participated in other clinical trials within 12 weeks prior to this study
6. Patients who received any drug by intra-articular injection for treatment within 2 months prior to this enrollment.
7. Patients who experienced as the knee joint cartilage and stem cell therapy or failure to treat
8. Patents who started or changed the physical therapy program established within 2 weeks before the start of the study or during the study(An established physical therapy program may continue for the duration of the trial, provided that it does not change in frequency and intensity)
9. Patents included in the following specific risk groups that may influence safety and efficacy assessments at the discretion of the investigator:: septic arthtritis, rheumatic disease, gout, recurrent pseudogout, paget disease, joint fracture, alcaptonuria, acromegaly, hemochromatosis, wilson's disease, primary osteochondrosis, hereditary disorder(ex: hyperkinesia), collagen gene abnormality ,etc
10. Patients who have clinically significant severe medical illnesses judged the principal investigator
11. Patients who have been diagnosed with malignancy within 5 years before screening (except for patients who were completely remissioned three years before screening criteria)
12. Patients who the principal investigator consider inappropriate for the clinical trial due to any other reasons
13. Patients who received concomitant contraindications and who have not passed the prescribed wash-out period before participating in the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Autologous Adipose Tissue derived MSCs; Biological: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml, 1 time injection(at 1week after high tibial osteotomy)	Biological: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml; biological : Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml drug: saline solution; Other Names: JOINTSTEM
NO_INTERVENTION: No treatment; No treatment (after high tibial osteotomy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI scan	MRI perform to measure cartilage defect size change from baseline up to 27 weeks	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI scan	MRI perform to measure cartilage defect size change from baseline up to 15 weeks	15, 27 weeks, 18, 24 months
WOMAC score	Change in WOMAC Total score from baseline up to 15, 27 weeks	15, 27 weeks, 18, 24 months
WOMAC sub-scale	Change in WOMAC sub-scale from baseline up to 15, 27 weeks	15, 27 weeks, 18, 24 months
Kellgren & Lawrence grade	Change in Kellgren & Lawrence grade from baseline up to 15, 27 weeks	15, 27 weeks, 18, 24 months
EQ5D	Change in the score of EQ-5D from baseline up to 15, 27 weeks	15, 27 weeks, 18, 24 months
ROM	change from baseline in knee flexion Range of Motion(ROM) at 15,27 weeks by physical examination	15, 27 weeks, 18, 24 months
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)	15, 27 weeks, 18, 24 months
PGIC(Patient Global Impression of Change)	The percentage of subjects who were evaluated as improved at 15 weeks and 27 weeks in the patient global impression of change	15, 27 weeks, 18, 24 months
PSQI(Pittsburgh Sleep Quality Index)	Change in PSQI from baseline up to 15, 27 weeks	15, 27 weeks, 18, 24 months
Biomarkers	Change from baseline in Biomarkers up to 15, 27 weeks	15, 27 weeks, 18, 24 months
Incidence of adverse reactions and characteristics associated with investigational product		15, 27 weeks, 18, 24 months

Collaborators and Investigators

• Sponsor: R-Bio

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 2, 2016
• Primary Completion (ACTUAL): May 22, 2020
• Study Completion (ACTUAL): May 22, 2020

Study Registration Dates

• First Submitted: December 18, 2016
• First Submitted That Met QC Criteria: December 18, 2016
• First Posted (ESTIMATE): December 22, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: osteoarthritis; Joint Diseases; Osteoarthritis, Knee; degenerative arthritis; biostar; Rbio; High tibial osteotomy; adipose tissue derived mesenchymal stem cell; kyung hee university hospital
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: HTO-MSCs

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO