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. (ARTROCELL)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Autologous MSCs; Drug: Allogenic MSCs; Drug: Hyaluronic Acid

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital Clínic
    • Contact: Andrés Comballa Aleu
    • Contact: Esperanza López Franco; Phone Number: +34 923 291100; Email: uicec.coordinacion@ibsal.es
  • Madrid, Spain
    • Suspended
    • Hospital Clinico Universitario San Carlos
  • Madrid, Spain
    • Recruiting
    • Hospital Fundación Jiménez Díaz
    • Contact: Esperanza López Franco; Phone Number: +34 923291100; Email: uicec.coordinacion@ibsal.es
  • Madrid, Spain
    • Recruiting
    • Hospital Gregorio Marañón
    • Contact: Esperanza López Franco; Phone Number: +34 923291100; Email: uicec.coordinacion@ibsal.es
  • Murcia, Spain
    • Recruiting
    • Hospital Universitario Virgen de la Arrixaca
    • Contact: Esperanza López Franco; Phone Number: 55779 +34 923291100; Email: uicec.coordinacion@ibsal.es
  • Málaga, Spain
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
    • Contact: Esperanza López Franco; Phone Number: +34 923291100; Email: uicec.coordinacion@ibsal.es
  • Pamplona, Spain
    • Recruiting
    • Clinica Universidad de Navarra
    • Contact: Esperanza López Franco; Phone Number: 923 291100; Email: uicec.coordinacion@ibsal.es
  • Salamanca, Spain, 37007
    • Recruiting
    • Complejo Asistencial Universitario de Salamanca
    • Contact: Esperanza López Franco; Phone Number: +34 923 291100; Email: uicec.coordinacion@ibsal.es
  • Valladolid, Spain
    • Active, not recruiting
    • Hospital Clínico Universitario de Valladolid

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Autologous Mesenchymal Stromal Cells (MSC); Treatment with 40 millions of autologous autologous adult mesenchymal stem cells from expanded bone marrow administered intra-articularly.	Drug: Autologous MSCs; Intra-articular injection 40 million/4 ml.
EXPERIMENTAL: Allogenic Mesenchymal Stromal Cells (MSC); Treatment with 40 millions of adult allogeneic expanded bone marrow mesenchymal stem cells administered intra-articularly.	Drug: Allogenic MSCs; Intra-articular injection 40 million/4 ml.
ACTIVE_COMPARATOR: Active Control; Hyaluronic Acid 60mg/3ml administered intra-articularly.	Drug: Hyaluronic Acid; Intra-articular injection 60mg / 3 ml .; Other Names: Hyaluronic Acid 20 mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 26, 2021
• Primary Completion (ANTICIPATED): December 1, 2025
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (ACTUAL): October 21, 2021

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: ARTROCELL; 2019-002446-21 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No