Back to resultsMulticenter 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)
Primary Purpose
Knee Osteoarthritis
Status
Recruiting
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Autologous MSCs
Allogenic MSCs
Hyaluronic Acid
Sponsored by
About this trial
This is an interventional treatment trial for Knee Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- Knee osteoarthritis Kellgren-Lawrence grade 2, 3 or 4 .
- Chronic painful knee of mechanical characteristics.
- Absence of local or systemic septic process.
- Hemacytometric and biochemical analysis without significant alterations that contraindicate treatment.
- Written informed consent of the patient.
- The patient is able to understand the nature of the study.
- NEGATIVE serologies: Syphilis, HTLVI-II, HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) and HCV Polymerase chain reaction (PCR) (must be repeated if more than 30 days elapse between its completion and the extraction of bone marrow in patients to whom autologous cells correspond).
- Body Mass Index 20-35 Kg/m2.
Exclusion Criteria:
- Patient < 18 years old, or legally dependent.
- Patient > 75 years old.
- Congenital or evolutive diseases that result in malformation and/or significant deformities of the knee (varus<10º; valgus<20º) that cause difficulties in the application and evaluation of the results.
- Pregnant or breastfeeding women.
- Neoplastic disease.
- Intra-articular infiltration of any drug in the 3 months prior to inclusion in the study.
- Concurrent participation in another clinical trial or treatment with another investigational product in the 30 days prior to inclusion in the study.
- Allergy to gentamicin (antibiotic used in the cell culture process).
- Other diseases or circumstances that may compromise the participation in the study according to medical criteria.
Sites / Locations
- Hospital Clinic
- Hospital Clínico Universitario San Carlos
- Hospital Fundación Jiménez DíazRecruiting
- Hospital Gregorio MarañónRecruiting
- Hospital Universitario Virgen de la ArrixacaRecruiting
- Hospital Universitario Virgen de la VictoriaRecruiting
- Clínica Universidad de NavarraRecruiting
- Complejo Asistencial Universitario de SalamancaRecruiting
- Hospital Clínico Universitario de Valladolid
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Autologous Mesenchymal Stromal Cells (MSC)
Allogenic Mesenchymal Stromal Cells (MSC)
Active Control
Arm Description
Treatment with 40 millions of autologous autologous adult mesenchymal stem cells from expanded bone marrow administered intra-articularly.
Treatment with 40 millions of adult allogeneic expanded bone marrow mesenchymal stem cells administered intra-articularly.
Hyaluronic Acid 60mg/3ml administered intra-articularly.
Outcomes
Primary Outcome Measures
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).
Pain self-assessment.
Evaluation of pain using Visual Analogue Scale (VAS) (Pain self-assessment score range from 0 -no pain- to 10 -maximum-).
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-)]
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.
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.
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).
Secondary Outcome Measures
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)]
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.
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.
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.
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
Full Information
NCT ID
NCT05086939
First Posted
July 5, 2021
Last Updated
February 7, 2023
Sponsor
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Collaborators
Instituto de Investigación Biomédica de Salamanca, Spanish Clinical Research Network - SCReN, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Universitari de Bellvitge
1. Study Identification
Unique Protocol Identification Number
NCT05086939
Brief Title
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.
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 26, 2021 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Collaborators
Instituto de Investigación Biomédica de Salamanca, Spanish Clinical Research Network - SCReN, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Universitari de Bellvitge
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Open-label, Clinical Trial comparing 3 active treatments.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Autologous Mesenchymal Stromal Cells (MSC)
Arm Type
Experimental
Arm Description
Treatment with 40 millions of autologous autologous adult mesenchymal stem cells from expanded bone marrow administered intra-articularly.
Arm Title
Allogenic Mesenchymal Stromal Cells (MSC)
Arm Type
Experimental
Arm Description
Treatment with 40 millions of adult allogeneic expanded bone marrow mesenchymal stem cells administered intra-articularly.
Arm Title
Active Control
Arm Type
Active Comparator
Arm Description
Hyaluronic Acid 60mg/3ml administered intra-articularly.
Intervention Type
Drug
Intervention Name(s)
Autologous MSCs
Intervention Description
Intra-articular injection 40 million/4 ml.
Intervention Type
Drug
Intervention Name(s)
Allogenic MSCs
Intervention Description
Intra-articular injection 40 million/4 ml.
Intervention Type
Drug
Intervention Name(s)
Hyaluronic Acid
Other Intervention Name(s)
Hyaluronic Acid 20 mg/ml
Intervention Description
Intra-articular injection 60mg / 3 ml .
Primary Outcome Measure Information:
Title
Range of motion.
Description
Evaluation of clinical-functional response using Joint range-of-motion evaluation (Flexion score 0º-140º / Extension score -140º-0º / Hyperextension: positive degrees from 0).
Time Frame
12 months
Title
Pain self-assessment.
Description
Evaluation of pain using Visual Analogue Scale (VAS) (Pain self-assessment score range from 0 -no pain- to 10 -maximum-).
Time Frame
12 months
Title
Knee Osteoarthritis.
Description
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-)]
Time Frame
12 months
Title
Functional response.
Description
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.
Time Frame
12 months
Title
X-ray changes of osteoarthritis.
Description
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.
Time Frame
12 months
Title
Radiological response using nuclear magnetic resonance imaging.
Description
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).
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Perceived general well-being.
Description
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)]
Time Frame
6, 12 and 24 months
Title
Feasibility assessment of a multicentre strategy production of both cell types with several Cell Production Units
Description
Rate of products not conforming to the validation criteria in each arm of experimental treatment.
Time Frame
24 months
Title
Evaluation of presence of adverse events related with investigational medical product (IMP).
Description
Rate of adverse events and other pharmacovigilance parameters in the three treatment arms.
Time Frame
24 months
Title
Evaluation of products obtained by genomic study and potency studies of the final products of all cell types (exploratory objective)
Description
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.
Time Frame
30 days
Title
Evaluate induced changes in circulating cells of the immune system after cell treatment (exploratory objetive)
Description
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
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Gonarthrosis grade 2, 3 or 4 of Kellgren and Lawrence (Kellgren & Lawrence, 1957) assessed by two observers.
Chronic painful knee of mechanical characteristics.
Absence of local or systemic septic process.
Hemat imetric and biochemical analysis without significant alterations that contraindicate the treatment.
Written informed consent of the patient.
The patient is able to understand the nature of the study.
Body Mass Index 20-35 Kg/m2.
Exclusion Criteria:
Patient < 18 years old, or legally dependent.
Patient > 75 years old.
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.
Pregnant or breastfeeding women.
Neoplastic disease.
Intra-articular infiltration of any drug in the 3 months prior to study inclusion.
Concurrent participation in another clinical trial or treatment with another investigational product within 30 days prior to study enrollment.
Allergy to gentamicin (antibiotic used in the cell culture process ).
Other diseases or circumstances that compromise participation in the study according to medical criteria.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fermín Sánchez-Guijo
Organizational Affiliation
IBSAL - University Hospital of Salamanca
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Clinic
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrés Comballa Aleu
First Name & Middle Initial & Last Name & Degree
Esperanza López Franco
Phone
+34 923 291100
Email
uicec.coordinacion@ibsal.es
First Name & Middle Initial & Last Name & Degree
Andrés Comballa Aleu
Facility Name
Hospital Clínico Universitario San Carlos
City
Madrid
Country
Spain
Individual Site Status
Suspended
Facility Name
Hospital Fundación Jiménez Díaz
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emilio Calvo Crespo
Phone
+34 915504800
Email
ecalvo@fjd.es
First Name & Middle Initial & Last Name & Degree
Esperanza López Franco
Phone
+34 923291100
Email
uicec.coordinacion@ibsal.es
First Name & Middle Initial & Last Name & Degree
Emilio Calvo Crespo
Facility Name
Hospital Gregorio Marañón
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Vaquero Martín
Phone
+34 915868000
Email
jvaquero@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
Esperanza López Franco
Phone
+34 923291100
Email
uicec.coordinacion@ibsal.es
First Name & Middle Initial & Last Name & Degree
Javier Vaquero Martín
Facility Name
Hospital Universitario Virgen de la Arrixaca
City
Murcia
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pedro A Martínez Victorio
Phone
+34 968369500
Email
pmartinezvi@secot.es
First Name & Middle Initial & Last Name & Degree
Esperanza López Franco
Phone
+34 923291100
Ext
55779
Email
uicec.coordinacion@ibsal.es
First Name & Middle Initial & Last Name & Degree
Pedro A. Martínez Victorio
Facility Name
Hospital Universitario Virgen de la Victoria
City
Málaga
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan M Gómez Palomo
Phone
+34 951032000
Email
jmgomezpalomo@gmail.com
First Name & Middle Initial & Last Name & Degree
Esperanza López Franco
Phone
+34 923291100
Email
uicec.coordinacion@ibsal.es
First Name & Middle Initial & Last Name & Degree
Juan M Gómez Palomo
Facility Name
Clínica Universidad de Navarra
City
Pamplona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Mª Lamo-Espinosa
Phone
+34 948 255400
Email
jlamodeespi@unav.es
First Name & Middle Initial & Last Name & Degree
Esperanza López Franco
Phone
923 291100
Email
uicec.coordinacion@ibsal.es
First Name & Middle Initial & Last Name & Degree
José Mª Lamo-Espinosa
Facility Name
Complejo Asistencial Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan F Blanco
Phone
+34 923 291100
Email
jfblanco@usal.es
First Name & Middle Initial & Last Name & Degree
Esperanza López Franco
Phone
+34 923 291100
Email
uicec.coordinacion@ibsal.es
First Name & Middle Initial & Last Name & Degree
Juan F Blanco
Facility Name
Hospital Clínico Universitario de Valladolid
City
Valladolid
Country
Spain
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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.
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