Clinical trial NCT05081921: Clinical Trial to Evaluate Safety and Efficacy of MesoCellA-Ortho Tissue-Engineered Advanced Therapy Product in Patients With Osteoarthrosis and Civilisation Diseases
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Osteoarthritis of Knee
Keywords: Osteoarthritis
Mesenchymal stem cells
Autologous stem cells
Adipose tissue
Type 2 diabetes
Obesity
Civilisation diseases
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
Collaborators: name: National Center for Research and Development, Poland
name: KCRI
First posted: 2021-10-18
Enrollment: 192
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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)

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).

Primary outcomes:
measure: Nature, incidence and severity of adverse events (AEs)
timeFrame: Month 6 Follow-up
measure: Change in Numerical Rating Scale (NRS)
timeFrame: Month 3 and Month 6 Follow-up
measure: Change in joint swelling
timeFrame: Month 3 and Month 6 Follow-up
measure: Change in the 36-Item Short Form Survey (SF-36)
timeFrame: Month 6 Follow-up
measure: Change in Knee injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: Month 3 and Month 6 Follow-up
measure: Change in the International Knee Documentation Committee (IKDC 2000)
timeFrame: Month 3 and Month 6 Follow-up
Secondary outcomes:
measure: Change in cartilage morphology
timeFrame: Month 6 Follow-up
measure: Change in cartilage T2 relaxation time mapping in MRI
timeFrame: Month 6 Follow-up
measure: Changes in bone marrow edema-like lesions (BMLs)
timeFrame: Month 6 Follow-up
measure: Change in weight distribution on stable platform
timeFrame: Month 6 Follow-up
measure: Change in Range of motion (ROM)
timeFrame: Month 6 Follow-up
measure: Change in ultrasonographic findings in knee joint
timeFrame: Month 3 and Month 6 Follow-up
Other outcomes:
Locations:
city: Bieruń
country: Poland
facility: Galen - Ortopedia Sp. Z O.O.
state: Silesia
Study officials:
affiliation: Galen Ortopedia Sp. z o. o
name: Krzysztof Ficek, Prof., MD, PhD, DSc
role: PRINCIPAL_INVESTIGATOR
References: