Adipose-derived Stem Cells (ADSCs) for Knee Osteoarthritis

A Phase I/II Study to Evaluate the Safety and Efficacy of the Allogeneic Injection of Expanded Adipose-derived Stem Cells to Patients With Knee Osteoarthritis

1. To assess the safety of allogeneic injection of expanded ADSCs to patients with knee osteoarthritis
2. To assess the efficacy of allogeneic injection of expanded ADSCs to patients with knee osteoarthritis

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: Elixcyte 8 ml; Device: Hya Joint Plus; Biological: Elixcyte 4 ml; Biological: Elixcyte 2 ml

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taoyuan City, Taiwan, 333
    • Chang Gung Memorial Hospital LinKou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 40-80 years (inclusive)
2. Kellgren-Lawrence grading I-III, as determined by American College of Rheumatology (ACR) criteria for osteoarthritis of the knee
3. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of 7-17 in the study knee even if treated with chronic doses of non steroidal anti-inflammatory drugs
4. Having provided informed consent

Exclusion Criteria:

1. With previous surgery of articular fracture, ligament reconstruction, meniscal reconstruction, and knee arthroplasty on the target knee joint
2. With previous intra-articular intervention on the target knee joint within past 3 months (e.g. steroid, anaesthetic, sodium hyaluronate)
3. Known or suspected infection of the target knee joint
4. Ascertained hypersensitivity to any component used in the study
5. Administered with systemic anti-inflammatory drugs (e.g. non-steroidal anti-inflammatory drug or steroid ) or topical anti-inflammatory drugs on target knee within 7 days prior to administration in the study
6. With serious prior or ongoing medical conditions (e.g. concomitant illness such as cardiovascular (e.g. New York Heart Association grade III or IV), hepatic (e.g. Child-Pugh Class C), psychiatric condition, alcoholism, drug abuse), medical history, physical findings, , or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely affect the safety of the patient
7. With any evidence of malignant disease with life expectancy of less than 1 year
8. Pregnant or lactating women or planning to be pregnant during the study period
9. With body mass index (BMI) greater or equal to 35 kg/m2
10. With joint diseases except knee osteoarthritis considered by investigator not eligible to enter the study
11. With known history of human immunodeficiency virus (HIV) infection.
12. Judged to be not applicable to this study by investigator such as difficulty of follow-up observation
13. With any other serious diseases/medical history considered by the investigator not in the condition to enter the trial
14. Having participated other investigational study within 4 weeks of entering this study
15. With known history of claustrophobia
16. Having any existing active/inactive implanted medical devices, such as cardiac pacemaker, cochlear, intracranial vascular clips or neurostimulator, etc...
17. Having any existing metallic intraocular foreign body

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elixcyte 8mL; ADSC 6.4*10^7 cells, allogeneic injection, one time injection on Day 1	Biological: Elixcyte 8 ml; ADSC 6.4*10^7 cells, allogeneic injection
Active Comparator: Hya Joint Plus; Hya Joint Plus synovial fluid supplement 3mL, SciVision Biotech Inc., one time injection on Day 1	Device: Hya Joint Plus; Hya Joint Plus synovial fluid supplement 3mL, SciVision Biotech Inc.
Experimental: Elixcyte 4mL; ADSC 3.2*10^7 cells, allogeneic injection, one time injection on Day 1	Biological: Elixcyte 4 ml; ADSC 3.2*10^7 cells, allogeneic injection
Experimental: Elixcyte 2mL; ADSC 1.6*10^7 cells, allogeneic injection, one time injection on Day 1	Biological: Elixcyte 2 ml; ADSC 1.6*10^7 cells, allogeneic injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes from baseline to post-treatment visit of WOMAC pain score at week 24 after treatment	Weeks 0, 24
Incidence of adverse events (AEs) and serious adverse events (SAEs)	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes from baseline to post-treatment visits of Visual Analogue Scale (VAS) to measure Pain Levels	Weeks 0, 2, 4, 12, 24, 36, 48
Changes from baseline to post-treatment visits of scores of sections in Knee Society Clinical Rating System (KSCRS) Score	Weeks 0, 2, 4, 12, 24, 36, 48
Changes from baseline to post-treatment visits of MRI examination results	Weeks 0, 24, 48, 72, 96
Changes from baseline to post-treatment visits of total score, and sub-scores of all sections in WOMAC	Weeks 0, 2, 4, 12, 36, 48
Total acetaminophen consumption amount during the first 48 weeks and week 48 to week 96	Week 0, 2, 4, 12, 24, 48, 96
Total non-steroidal anti-inflammatory drug (NSAID) consumption amount during the first 48 weeks and week 48 to week 96	Weeks 0, 2, 4, 12, 24
Time to subject first time consumes acetaminophen	Weeks 0, 2, 4, 12, 24
Time to subject first time consumes non-steroidal anti-inflammatory drug (NSAID)	Weeks 0, 2, 4, 12, 24
Number of patients with clinically abnormal laboratory values and/or adverse events that are related to treatment	Weeks 0, 2, 4, 12, 24, 36, 48, 72, 96
Number of patients with clinically abnormal vital signs and/or adverse events that are related to treatment	Weeks 0, 2, 4, 12, 24, 36, 48, 72, 96
Changes from baseline to week 96 visit in cartilage thickness in the total femorotibial joint by centralized (independent) imaging interpretation.	Weeks 0, 24, 48, 72, 96

Collaborators and Investigators

• Sponsor: UnicoCell Biomed CO. LTD
• Collaborators: A2 Healthcare Taiwan Corporation
• Investigators: Principal Investigator: Yu-Han Chang, MD, Chang Gung Memorial Hospital; Principal Investigator: Cheng-Fong Chen, MD, Taipei Veterans General Hospital, Taiwan

Publications and helpful links

General Publications

• Chen CF, Hu CC, Wu CT, Wu HH, Chang CS, Hung YP, Tsai CC, Chang Y. Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE(R): a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial. Stem Cell Res Ther. 2021 Oct 30;12(1):562. doi: 10.1186/s13287-021-02631-z.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: May 16, 2016
• First Submitted That Met QC Criteria: May 24, 2016
• First Posted (Estimate): May 27, 2016

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: July 14, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: CT21

Plan for Individual participant data (IPD)

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