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

Phase 1

• Conditions: Knee Osteoarthritis
• Interventions: Biological: Bone marrow-derived MMSCs; Biological: Placenta-derived MMSCs; Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe

• Registration Number: NCT04453111
• Lead Sponsor: Institute of Cell Therapy

Brief Summary

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.

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 Timeline

• Study Start: 2020-01-02
• Study First Submitted: 2020-06-15
• Study First Submitted QC: 2020-06-26
• Status Verified: 2020-07
• Study First Posted: 2020-07-01
• Last Update Submitted: 2020-07-01
• Last Update Posted: 2020-07-07
• Primary Completion: 2021-08
• Study Completion: 2021-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hyaluronic Acid (HA) + BM-MMSCs	Bone marrow-derived 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
Hyaluronic Acid (HA) + P-MMSCs	Hyalgan 20 mg in 2 ML Prefilled Syringe	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
Hyaluronic Acid (HA) + P-MMSCs	Placenta-derived 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
Hyaluronic Acid (HA)	Hyalgan 20 mg in 2 ML Prefilled Syringe	Three intra-articular injection of 20 mg Hyaluronic Acid - 15 patients
Hyaluronic Acid (HA) + BM-MMSCs	Hyalgan 20 mg in 2 ML Prefilled Syringe	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Radiographic evidence. Whole-Organ Magnetic Resonance Imaging Score (WORMS)	12 months	Change in cartilage thickness of the knee using MRI
The Visual Analog Scale (VAS) assessment	12 months	VAS - measure of pain intensity. The scale is most commonly anchored by "no pain " (score of 0) and "worst imaginable pain" (score of 10).
Physical function improvement measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC).	12 months.	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.
Quality of Life (QOL) assessment	12 months	Change in scores on the QOL

Trial Locations

Locations (1)

Institute of Cell Therapy; 🇺🇦 Kyiv, Ukraine