articular knee diseases MedDRA version: 21.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: MesoCellA-Ortho
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Autologous adipose-derived mesenchymal stem cells in vitro expanded
Other descriptive name: Autologous
Sponsors
Jagiellonian University
Eligibility
Sex/Gender
All
Inclusion criteria
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) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
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: i)HIV, syphilis, HBV, HCV ii) CMV, mycoplasmas (only subjects with positive results for IgM antibodies will be excluded) iii) medical history or diagnosed during anamnesis/medical examination: EBV, malaria, Toxoplasma gondii, Trypanosoma cruzi, HTLV. 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. At screening: • blood test result outside of the allowable ranges (e. g. morphology, electrolytes, blood clotting APTT, INR, fibrinogen, CRP, glucose) • positive results of laboratory blood test (HIV, syphilis, HBV, HCV, CMV-IgM, mycoplasmas-IgM) 20. 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. 21. Known allergic reactions to antibiotics used in cell culture: penicillin, streptomycin, amphotericin B. 22. Intolerance or hypersensitivity to any of the anesthetics (including lignocaine).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety: •To establish the safety of hyaluronic acid supplemented with AT-MSCs (MesoCellA-Ortho) injected intraarticular at a dose of 20 mln cells over 6 months by monitoring adverse reactions in three group of patients with osteoarthritis, additionally burdened with obesity and type 2 diabetes. Clinical efficacy: •To evaluate efficacy of treatment of osteoarthritis (OA) with autologous AT-MSCs (MesoCellA-Ortho) when compared to treatment method employing hyaluronic acid intraarticular injection in non-obese patients and in patients burdened with T2DM and obesity, considering patient’s subjective pain level and evaluation of the improvement of knee joint function. osteoarthrosis treatment, through subjective patient assessment of knee function and pain level.;Secondary Objective: Clinical efficacy: •To evaluate efficacy of treatment of osteoarthritis (OA) with autologous AT-MSCs (MesoCellA-Ortho) when compared to treatment method employing hyaluronic acid intraarticular injection in non-obese patients and patients burdened with T2DM and obesity, considering changes in cartilage structure observed in MRI, as well as objective improvement of knee joint function assessed by dynamographic platform and ROM. ;Primary end point(s): Safety Endpoints The primary endpoint of this study is to measure the number and frequency of adverse event(s) including serious adverse event(s) throughout the study duration. Therefore, the following data will be collected: Primary: •Nature, incidence and severity of adverse events and serious adverse events, •Numerical Rating Scale (NRS) – evaluation of changes in pain level under the influence of intraarticular injection of MesoCellA-Ortho (according to Table 1) •Joint swelling (physical examination) - evaluation the joint swelling by physical examination after intraarticular injection •Allergic reactions Efficacy Endpoints The efficacy endpoint of this study is to measure positive effect of the proposed therapy in k | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • MRI – qualitative and quantitative assessment of cartilage: - evaluation of the cartilage by modified Outerbridge (Modified Outerbridge classification of cartilage defects), - cartilage mapping: measurement of relaxation time (measured in milliseconds, ms) in selected ROIs (Region of Interest) in both medial and lateral femoral and tibial condyle, - subchondral bone evaluation: observation of bone marrow edema-like lesions (BMLs) in medial and lateral femoral and tibial condyle; if present then measurement of width and length of BMLs in sagittal cross-sections. • Dynamographic platform – weight distribution on stable platform for objective evaluation of lower limb loading symmetry during clinical study during 5 exercises: standing, standing with eyes closed, calf raises, squat, jump. Minimum, maximum and average weight-bearing value (measured in kilograms, kg) of the left and right lower extremity will be recorded. • Range of motion (ROM) - measurement of knee flexion and extension angles. Normal ROM at the knee is considered to be 0 degrees of extension (completely straight knee joint) to 135 degrees of flexion (fully bent knee joint). ;Timepoint(s) of evaluation of this end point: pre-rehabilitation visit 1, intraarticular administration visit, rehabilitation visit 4, follow-up visit 1, follow-up visit 2 | — |
Countries
Poland
Contacts
Public ContactBiuro Projektu BioMiStem
Ewa Zuba-Surma
Outcome results
None listed