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.

Knee Osteoarthritis Clinical Trial

— ARTROCELL  

Official title:

Phase III, Multicenter, Randomized, Open-label Clinical Trial Comparing Treatment With Allogeneic Mesenchymal Cells Versus Autologous Mesenchymal Cells and Versus Active Control With Hyaluronic Acid in Patients With Knee Osteoarthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05086939
• Other study ID #: ARTROCELL
• Secondary ID: 2019-002446-21
• Status: Recruiting
• Phase: Phase 3
• Start date: May 26, 2021
• Est. completion date: December 2025

Study information

• Verified date: February 2023
• Source: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Autologous MSCs
Intra-articular injection 40 million/4 ml.
• Allogenic MSCs
Intra-articular injection 40 million/4 ml.
• Hyaluronic Acid
Intra-articular injection 60mg / 3 ml .

Locations

Country	Name	City	State
Spain	Hospital Clinic	Barcelona
Spain	Hospital Clínico Universitario San Carlos	Madrid
Spain	Hospital Fundación Jiménez Díaz	Madrid
Spain	Hospital Gregorio Marañón	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Complejo Asistencial Universitario de Salamanca	Salamanca
Spain	Hospital Clínico Universitario de Valladolid	Valladolid

Sponsors (5)

Lead Sponsor	Collaborator
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León	Hospital Universitari de Bellvitge, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Instituto de Investigación Biomédica de Salamanca, Spanish Clinical Research Network - SCReN

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Range of motion.	Evaluation of clinical-functional response using Joint range-of-motion evaluation (Flexion score 0º-140º / Extension score -140º-0º / Hyperextension: positive degrees from 0).	12 months
Primary	Pain self-assessment.	Evaluation of pain using Visual Analogue Scale (VAS) (Pain self-assessment score range from 0 -no pain- to 10 -maximum-).	12 months
Primary	Knee Osteoarthritis.	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-)]	12 months
Primary	Functional response.	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.	12 months
Primary	X-ray changes of osteoarthritis.	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.	12 months
Primary	Radiological response using nuclear magnetic resonance imaging.	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).	12 months
Secondary	Perceived general well-being.	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)]	6, 12 and 24 months
Secondary	Feasibility assessment of a multicentre strategy production of both cell types with several Cell Production Units	Rate of products not conforming to the validation criteria in each arm of experimental treatment.	24 months
Secondary	Evaluation of presence of adverse events related with investigational medical product (IMP).	Rate of adverse events and other pharmacovigilance parameters in the three treatment arms.	24 months
Secondary	Evaluation of products obtained by genomic study and potency studies of the final products of all cell types (exploratory objective)	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.	30 days
Secondary	Evaluate induced changes in circulating cells of the immune system after cell treatment (exploratory objetive)	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	30 days