Clinical Study of Intra Articular Injection of Catholic MASTER Cell (Bone Marrow Derived Mesenchymal Stem Cell) in Knee Osteoarthritis (MSC-OA)

Randomized Double-blind Clinical Study of Intra Articular Injection of Catholic MASTER Cell in Knee Osteoarthritis

1. objective

   - safety and efficacy evalaution of MASTER cells injected into knee of patients with osteoarthritis

2. background

   • osteoarthritis

     • Osteoarthritis is severe and intractable musculoskeletal disease that eventually leads to joint failure and pain due to inflammation and joint injury.
     • OA is one of the most prevalent diseases. The prevalence increases with age, but overuse and trauma can result in OA in young population as well.
     • Injured cartilage can not be regenerated spontaneously, untreated injured cartilage eventually leads to osteoarthritis. Surgical treatment may repair the damage but the reparied cartilage may turn out to be fibrocartilage rather than hyaline cartilage.

   • Curent treatment

     • medical therapy: medication for symptom relief, together with exercise. Medications include NSAIDS visco-supplement.
     • surgical therapy: total knee replacement arthroplasty
     • to overcome such limitations, cell therapy such as stem cell/ chondrocyte injection is being investigated

3. Hypothesis

   - Intra articular injection of MASTER cells will show safety and efficacy in terms of pain and functional improvement.

4. Protocol 1) deisgn : Injection of MASTER cell 1X 10^8 cells/2cc (experimental arm) or 2cc saline (placebo arm) into knee of patients with osteoarthritis 2) outcomes

   • primary outcome : safety evaluation(adverse event)
   • secondary outcomes : check on 1,2,3,6,9,12 months, atient reported outcome (WOMAC, KOOS, IKDC, pain VAS) 3,12 months SF-36, knee MRI score, serum cytokine, bone turnover marker 12 months x-ray 3) Disease

   • osteoarthritis

     4) Subjects

     1. inclusion : age 20-80yrs, diagnosed with OA according to ACR criteria for knee OA, baseline pain VAS equal or more than 50mm
     2. exclusion: lower extremities surgery within 6months or planned surgery, concommitant systemic rheumatic diseases that can affect the results of the trial, steroid intraarticular inejction into the index knee within 3months, clinicallly meaningful abnormal lab tests (liver function, kidney function)

     5) evaluation

   • primary outome : compare the number and proportion of of adverse event and lab test abnormalities between the two arms

   • secondary outome

     1. change of 100mm pain VAS
     2. change of Western Ontario and McMAster Universities Osteoarthritis (WOMAC) pain VAS, IKDC, KOOS total score
     3. change WOMAC sub scale, IKDC, KOOS
     4. chagne of KHAQ
     5. change of MRI indices
     6. change of x-ray( joins space narrowing)
     7. change of serum ESR/CRP, CTX-II

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Biological: Catholic MASTER cell; Other: Saline

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ji Hyeon Ju, MD, PhD; Phone Number: 82-2-2258-6893; Email: juji@catholic.ac.kr
• Study Contact Backup: Name: Jennifer Lee, MD, PhD; Phone Number: 82-2-2258-6893; Email: poohish@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06950
    • Recruiting
    • Catholic University of Korea
    • Contact: Ji Hyeon Ju, MD, PhD

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. Age 20-80
2. diagnosed with knee osteoarthritis (OA) according to ACR classfication criteia for knee OA
3. symptomatic OA that lastede for at least 3 months before screening
4. Baseline Pain VAS ≥50 mm
5. treated with medication such as acetaminophen, tramadol, NSAID for at least 1month due to OA pain
6. X-ray Kellgren-Lawrence grade 1~4
7. volauntarily enrolled with informed consent
8. no improvement with medical treatment for at least 3 months

Exclusion Criteria:

1. disease in spine or lower extremities that can affect the outcome of index knee
2. surgery on lower extremities within 6month before injection or planned
3. joint symptoms that can affect the interpretation of the trial data or prevent the subject from enrollement including but not limited to symptomatic fracture, fibromyalgia, rheumatoid arthritis, reactive arthritis
4. steroid injection to the index knee within preivious 3months
5. hyaluronic acid injection to the index knee within preivious 6months
6. underwent cell therapy or gene therapy in the past
7. more than 3 times upper normal limit in one or more of the followings: serum creatinine, bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or more than 3 times upper normal limit in two or more of the followings: bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
8. participation in a different clinical trial other than this within 4 weeks after initiation of the current study
9. use (reccuent use or addiction) of substances that can affect pain sensation such as narcotics
10. females of childbearing age who do not consent to effective contraceptive methods during the study period
11. pregnant or lactating woman
12. malignancy
13. considered to be inappropriate for the trial by investigators

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: MASTER cell; Intraarticular injection of Catholic MASTER cell, 1 time, 1 x 10^8 cells/DMEM 5cc, into knee joint of patients with osteoarthritis	Biological: Catholic MASTER cell; Injection of CATHOLIC MASTER cells 1 x 10^8 cells/DMEM 5cc into knee of patents with osteoarthritis
Placebo Comparator: Saline; Intraarticular injection of saline, 1 time, 5cc, into knee joint of patients with osteoarthritis	Other: Saline; Injection of saline 5cc into knee of patents with osteoarthritis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
adverse event according to CTCAE 5.0, clinically meaningful abnormalites in laboratory tests (blood)	Change from Baseline blood abnormalities at 12 month
Western Ontario and McMaster Universities Arthritis Index (WOMAC) score	Change from Baseline WOMAC score at 12 month
Knee injury and Osteoarthritis Outcome Score (KOOS)	Change from Baseline KOOS score at 12 month
International knee documentation committee (IKDC)	Change from Baseline IKDC score at 12 month
Cartilage damage evaluation through knee MRI	Change from Baseline cartilage morphology at 12 month
SF-36 questionnaire	Change from Baseline SF-36 score at 12 month
Serum inflammatory cytokine, acute phase reactant, bone turnover marker	Change from Baseline cytokine level, acute phase reactant, bone turnover marker level at 12 month
Cartilage damage evaluation through knee x-ray	Change from Baseline cartilage and bone morphology at 12 month

Collaborators and Investigators

• Sponsor: Seoul St. Mary's Hospital
• Investigators: Principal Investigator: Ji Hyeon Ju, MD, PhD, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2019
• Primary Completion (Anticipated): March 31, 2021
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: January 22, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: osteoarthritis; mesenchymal stem cell
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: KC19CNSI0469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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