Clinical Trial to Evaluate Safety and Efficacy of MesoCellA-Ortho Tissue-Engineered Advanced Therapy Product in Patients With Osteoarthrosis and Civilisation Diseases

A Randomized, Double Blind, Two Arms, Controlled Phase I/II Safety and Efficacy Study on MesoCellA-Ortho Tissue Engineered Product Intraarticularly Administrated in Adult Patients With Osteoarthrosis

The aim of the study is to evaluate safety, tolerability and clinical efficacy of a newly developed MesoCellA-Ortho tissue-engineered advanced therapy medicinal product in adult patients suffering with osteoarthritis and additionally burdened with other civilisation diseases such as type 2 diabetes and/ or obesity.

The active substance of MesoCellA-Ortho consists of in vitro expanded autologous human adipose tissue-derived mesenchymal stem/ stromal cells (AT-MSCs) resuspended in carrier solution for intraarticular injections for individual patents.

To evaluate safety, tolerability and clinical efficacy of a MesoCellA-Ortho product, the active substance of MesoCellA-Ortho consisting of 20 mln in vitro expanded autologous human adipose tissue-derived mesenchymal stem/ stromal cells (AT-MSCs) will be intraarticularly administrated in adult patients with osteoarthritis and additionally burdened with other civilisation diseases such as type 2 diabetes and/ or obesity. Hyaluronic acid (HA) will be used as a Control.

The safety and clinical outcome of the treatment will be evaluated during 6 months of followup, considering patient's subjective pain level and evaluation of the improvement of knee joint function.

Inclusion Criteria:

1. Knee cartilage lesions (osteoarthritis II/III grade in Kellgren-Lawrence scale confirmed in X-ray)
2. Age between 40-70 years (inclusive)
3. No contraindications for liposuction
4. No contraindications for the general use of biological treatment, stem cells, PRP and whole autologous blood
5. Availability to take part into all study visits, barring unforeseen circumstances
6. Able and willing to perform exercises at home given by a physiotherapist
7. Contraceptive (birth control pills, injection, pessary or intrauterine device (IUD), spermicide condoms)
8. The pain intensity in treated knee not lower than grade 3 (on 11-point Numerical Rating Scale)

Exclusion Criteria:

1. A history of cancer for 2 years before screening. In case of history of cancer medical above 2 years, consultation with oncologist and her/his permission for participation in clinical trial will be obligatory.

2. Pregnant or breastfeeding women.

3. Allergy or poor tolerance of hyaluronic acid.

4. Diabetes mellitus type 1, diabetes mellitus type 2 on insulin treatment.

5. Lack of medical consultation in case of patients with diabetes group.

6. Comorbidities significantly affecting overall health (e.g. history of myocardial infarction, heart failure, thrombophlebitis, arterial hypertension (hypertensive crises), chronic obstructive pulmonary disease, renal failure, liver failure, advanced atherosclerosis, psychoorganic syndrome, hemiparesis, history of stroke).

7. Current or medical history of the patient: inflammatory diseases of the joints (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative arthritis involving the spine joints, septic arthritis, prior diagnosis of target arthrosis with crystal precipitation or elevated CRP in the condition, inflammation), osteonecrosis, osteoporotic fractures or other painful joint diseases other than osteoarthritis; secondary causes of osteoarthritis (e.g. rheumatoid arthritis, fibromyalgia, birth defects).

8. Current or medical history of the patient concerning carrier state or diseases: HIV, syphilis, HBV, HCV, EBV.

9. Symptomatic sciatica with radiation of pain to the examined limb.

10. Symptomatic osteoarthritis of the hip of both limbs.

11. Significant knee injuries within 6 months such as: ligament injuries, distal femur fracture or proximal tibia fracture, arthrofibrosis or cyclops lesions.

12. Endoprosthesis of the hip or knee joints.

13. Partial / total knee or hip joints replacement planned during the study.

14. Surgical operation of the lower limbs (including arthroscopy) within 6 months before screening visit or planned during the study.

15. Constant use of orthopaedic aids.

16. Intolerance or hypersensitivity to any component of the preparation.

17. Use of alternative treatment methods i.e. acupuncture within 4 weeks before screening visit or planning their use during the study.

18. Use in the treatment of osteoarthritis:

    • Hyaluronates (injections - test knee) within 3 months
    • Corticosteroids (injections) within 3 months
    • Oral corticosteroids within 3 months

19. If available, recent (<14 days) blood tests results outside of the allowable ranges (e. g. morphology, electrolytes, blood clotting APTT, INR, fibrinogen, CRP, glucose) if significant for participation in clinical study, particularly regarding contraindication for liposuction procedure.

20. If available, positive results of laboratory blood tests (HIV, syphilis, HBV, HCV, CMV -IgM antibodies, mycoplasmas -IgM antibodies, toxoplasmosis IgM antibodies, EBV IgM antibodies) if significant for participation in clinical study, particularly regarding contraindication for liposuction procedure.

21. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.

22. Known allergic reactions to antibiotics used in cell culture: penicillin, streptomycin, amphotericin B.

23. Intolerance or hypersensitivity to any of the anesthetics (including lignocaine).