Efficacy of Bone-marrow-derived and Placenta-derived Multipotent Mesenchymal Stem / Stromal Cells for Osteoarthritis

To define the clinical effects of intra-articular transplantation of bone-marrow-derived (BM-MMSCs) and placenta-derived multipotent mesenchymal stem / stromal cells (P-MMSCs) for knee osteoarthritis.

Study Overview

• Status: Unknown
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: Placenta-derived MMSCs; Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe; Biological: Bone marrow-derived MMSCs

Detailed Description

Multipotent mesenchymal stem / stromal cells (MMSCs) of different origin are the novel therapeutic agents that can slow down cartilage degeneration, improve reparation and ultimately prevent joint prosthetics. MSCs are capable to direct differentiation into chondrocytes, produce cytokines and growth factors with immunomodulatory and anti-inflammatory effects, stimulate angiogenesis, as well as induce chemotaxis of endogenous progenitors. Bone marrow-derived and placenta-derived MMSCs can be considered the most promising source for cell therapy of joints disorders according to availability, safety and expected therapeutic efficacy.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine, 04073
    • Recruiting
    • Institute of Cell Therapy
    • Contact: Vitalii Kyryk, PhD; Phone Number: +380442079207; Email: kyryk@stemcellclinic.com
    • Principal Investigator: Evgen Goliuk, MD, PhD
    • Principal Investigator: Roman Birsa, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical diagnosis of knee osteoarthritis.
2. Age: 18 to 75 years old.
3. Kellgren-Lawrence Grade 2 or 3 according to X-ray imaging.
4. Knee pain.
5. Written informed consent

Exclusion Criteria:

1. Age <18 or >75 years of age by time of infusion.
2. Participation in an on-going investigational therapeutic or device trial 30 days of consent.
3. Rheumatoid arthritis.
4. Psoriatic arthritis.
5. Juvenile idiopathic arthritis.
6. Gout.
7. Infectious arthritis.
8. Osteomyelitis.
9. Osteonecrosis.
10. Inflammatory arthritis.
11. Chondropathy.
12. Joint contracture.
13. Arthroplasty.
14. Arthroscopy within 6 months prior to study entry.
15. Intra-articular injection within 3 months prior to study entry.
16. Hormone intake.
17. Antiaggregants and anticoagulants intake.
18. Immunosuppressants intake.
19. Allergy to hyaluronic acid.
20. History of organ or cell transplantation.
21. Hematologic abnormality evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet count < 100,000/ul.
22. Active infection.
23. Positive for HIV antigen.
24. History of hepatitis B, hepatitis C.
25. History of malignancy in the last 5 years prior to study entry.
26. Active tumors.
27. History of myocardial infarction.
28. History of stroke.
29. Renal failure with chronic hemodialysis.
30. Liver Cirrhosis (ICGR 15 >30%).
31. Chromosomal abnormality.
32. Peripheral nervous system disorders.
33. Cognitive or language barriers that prohibit obtaining informed consent or any study elements.
34. History of drug abuse or alcohol abuse, or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months.
35. Pregnant/nursing women or women of child-bearing potential.
36. Other condition that limits lifespan to < 1 year.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hyaluronic Acid (HA) + P-MMSCs; Experimental Group 1: Three intra-articular injection of allogeneic P-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients	Biological: Placenta-derived MMSCs; Cryopreserved placenta-derived multipotent mesenchymal stem / stromal cells; Other Names: P-MMSCs; Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe; Hyaluronic Acid 20 mg; Other Names: HA
EXPERIMENTAL: Hyaluronic Acid (HA) + BM-MMSCs; Experimental Group 2: Three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients	Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe; Hyaluronic Acid 20 mg; Other Names: HA; Biological: Bone marrow-derived MMSCs; Cryopreserved bone marrow-derived multipotent mesenchymal stem / stromal cells; Other Names: BM-MMSCs
ACTIVE_COMPARATOR: Hyaluronic Acid (HA); Three intra-articular injection of 20 mg Hyaluronic Acid - 15 patients	Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe; Hyaluronic Acid 20 mg; Other Names: HA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events and changes in physical examinations, vital signs and the results of clinical lab tests.	Treatment-related adverse events	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical function improvement measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC).	Change in joint function from baseline WOMAC assessment. The WOMAC used a scoring scale of 0-4 (lower scores indicate lower levels of symptoms or physical disability). The higher the score, the higher the amount of pain, stiffness, and a high level of functional limitations.	12 months.
Radiographic evidence. Whole-Organ Magnetic Resonance Imaging Score (WORMS)	Change in cartilage thickness of the knee using MRI	12 months
Quality of Life (QOL) assessment	Change in scores on the QOL	12 months
The Visual Analog Scale (VAS) assessment	VAS - measure of pain intensity. The scale is most commonly anchored by "no pain " (score of 0) and "worst imaginable pain" (score of 10).	12 months

Collaborators and Investigators

• Sponsor: Institute of Cell Therapy
• Collaborators: The Institute of Traumatology and Orthopedics of NAMS of Ukraine; Kyiv City Clinical Hospital № 6

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 2, 2020
• Primary Completion (ANTICIPATED): August 1, 2021
• Study Completion (ANTICIPATED): October 1, 2021

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (ACTUAL): July 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Hyaluronic Acid; BM-MMSCs;; P-MMSCs
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: #7/09.26.2018

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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