Knee Osteoarthritis
Conditions
Brief summary
Phase III, multicenter, randomized, open-label, multicenter clinical trial comparing treatment with allogeneic mesenchymal cells versus autologous mesenchymal cells and versus active control with hyaluronic acid in patients with knee osteoarthritis.
Interventions
DRUGAutologous MSCs
Intra-articular injection 40 million/4 ml.
DRUGAllogenic MSCs
Intra-articular injection 40 million/4 ml.
DRUGHyaluronic Acid
Intra-articular injection 60mg / 3 ml .
Sponsors
Instituto de Investigación Biomédica de Salamanca
Spanish Clinical Research Network - SCReN
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Hospital Universitari de Bellvitge
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, Open-label, Clinical Trial comparing 3 active treatments.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Gonarthrosis grade 2, 3 or 4 of Kellgren and Lawrence (Kellgren & Lawrence, 1957) assessed by two observers. 2. Chronic painful knee of mechanical characteristics. 3. Absence of local or systemic septic process. 4. Hemat imetric and biochemical analysis without significant alterations that contraindicate the treatment. 5. Written informed consent of the patient. 6. The patient is able to understand the nature of the study. 7. Body Mass Index 20-35 Kg/m2.
Exclusion criteria
1. Patient \< 18 years old, or legally dependent. 2. Patient \> 75 years old. 3. Congenital or developmental diseases that translate malformation and / or significant deformations of the knee (varus\>10º; valgus\>20º) and condition difficulties of application and evaluation of the results. 4. Pregnant or breastfeeding women. 5. Neoplastic disease. 6. Intra-articular infiltration of any drug in the 3 months prior to study inclusion. 7. Concurrent participation in another clinical trial or treatment with another investigational product within 30 days prior to study enrollment. 8. Allergy to gentamicin (antibiotic used in the cell culture process ). 9. Other diseases or circumstances that compromise participation in the study according to medical criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiological response using nuclear magnetic resonance imaging. | 12 months | Evaluation of radiological response using T2 mapping nuclear magnetic resonance imaging (screening visit global mean of T2 values versus 12 months visit global mean of T2 values). |
| Range of motion. | 12 months | Evaluation of clinical-functional response using Joint range-of-motion evaluation (Flexion score 0º-140º / Extension score -140º-0º / Hyperextension: positive degrees from 0). |
| Pain self-assessment. | 12 months | Evaluation of pain using Visual Analogue Scale (VAS) (Pain self-assessment score range from 0 -no pain- to 10 -maximum-). |
| Knee Osteoarthritis. | 12 months | Evaluation of Knee Osteoarthritis using Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) \[measures five items for pain (score range from 0 -no pain- to 20 -maximum-), two for stiffness (score range from 0-no stiffness- to 8 -maximum-), and 17 for functional limitation (score range from 0 -no limitation- to 68 -maximum-)\] |
| Functional response. | 12 months | Evaluation of functional response using Lequesne Algofunctional Index (score range from 0 to 24). It includes measures of pain (5 questions), walking distance (1 question) and activities of daily living (4 questions) with separate versions for the hip and knee. The scores for each question are summed to obtain a combined score of disease severity. Scores 1 to 4 are classified as mild osteoarthrosis; 5 to 7, moderate; 8 to 10, severe; 11 to 13, very severe; and 14 and above, extremely severe. |
| X-ray changes of osteoarthritis. | 12 months | Radiological response using Kellgren and Lawrence classification system (grade from 0 to 4): * grade 0 (none): definite absence of x-ray changes of osteoarthritis. * grade 1 (doubtful): doubtful joint space narrowing and possible osteophytic lipping. * grade 2 (minimal): definite osteophytes and possible joint space narrowing. * grade 3 (moderate): moderate multiple osteophytes, definite narrowing of joint space and some sclerosis and possible deformity of bone ends. * grade 4 (severe): large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone ends. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility assessment of a multicentre strategy production of both cell types with several Cell Production Units | 24 months | Rate of products not conforming to the validation criteria in each arm of experimental treatment. |
| Evaluation of presence of adverse events related with investigational medical product (IMP). | 24 months | Rate of adverse events and other pharmacovigilance parameters in the three treatment arms. |
| Evaluation of products obtained by genomic study and potency studies of the final products of all cell types (exploratory objective) | 30 days | Studies of the cell product. In this exploratory objective, genomic studies will be carried out using RNA-seq and open array on the advanced therapy drugs manufactured in the study (both autologous and allogeneic), and a correlation will be made with clinical and biological parameters and with the response. |
| Evaluate induced changes in circulating cells of the immune system after cell treatment (exploratory objetive) | 30 days | Evaluation of cell populations (NK cells, B cells, regulatory T cells, myeloid suppressor cells, T cell populations) by flow cytometry, prior to administration of cell therapy, at 7 days and 30 days. Evaluation of activation and inhibition markers in T lymphocytes (CD69, HLADR, CD137, PD1, LAG3 and TIM3) prior to administration of cell therapy, at 7 days and 30 days Population of inflammatory cytokines circulating in peripheral blood (Plex deB iorad -reference M50DKFADY), prior to administration of treatment, at 7 days and 30 days |
| Perceived general well-being. | 6, 12 and 24 months | Evaluation of quality of life using Short Form-12 Health Survey questionnaire (SF12) \[score range from 0 (the worst health status for that dimension) to 100 (the best health status)\] |
Countries
Spain
Outcome results
None listed