Knee OsteoarthritisPhase 3ARTROCELLNCT05086939
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.
A Phase 3 study testing Autologous MSCs, Allogenic MSCs and Hyaluronic Acid in people with Knee Osteoarthritis, run by Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León at 8 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Autologous MSCs, Allogenic MSCs and Hyaluronic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 8 sitesSpain
- Study dates
- 26 May 2021to May 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Spain8 sites
Hospital Clinic
Barcelona
Hospital Clínico Universitario San Carlos
Madrid
Hospital Fundación Jiménez Díaz
Madrid
Hospital Gregorio Marañón
Madrid
Hospital Universitario Virgen de la Victoria
Málaga
Hospital Universitario Virgen de la Arrixaca
Murcia
Clínica Universidad de Navarra
Pamplona
Complejo Asistencial Universitario de Salamanca
Salamanca, 37007
About this study
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
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.
- Conditions
- Knee Osteoarthritis
- Being tested
- Autologous MSCs, Allogenic MSCs, Hyaluronic Acid
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous MSCsDrug
Intra-articular injection 40 million/4 ml.
Allogenic MSCsDrug
Intra-articular injection 40 million/4 ml.
Hyaluronic AcidDrug
Also called Hyaluronic Acid 20 mg/ml
Intra-articular injection 60mg / 3 ml .
| Study group | Role | What they receive |
|---|---|---|
| Autologous Mesenchymal Stromal Cells (MSC) | Experimental | Treatment with 40 millions of autologous autologous adult mesenchymal stem cells from expanded bone marrow administered intra-articularly. Receives: Drug: Autologous MSCs |
| Allogenic Mesenchymal Stromal Cells (MSC) | Experimental | Treatment with 40 millions of adult allogeneic expanded bone marrow mesenchymal stem cells administered intra-articularly. Receives: Drug: Allogenic MSCs |
| Active Control | Active comparator | Hyaluronic Acid 60mg/3ml administered intra-articularly. Receives: Drug: Hyaluronic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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-).
Measured: 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-)]
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 12 months
Secondary outcomes (5)
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)]
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2021
- Study start26 May 2021
- Primary completionMay 2025 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Open-label, Clinical Trial comparing 3 active treatments.
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Investigación Biomédica de Salamanca, Spanish Clinical Research Network - SCReN, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Universitari de Bellvitge
- Responsible party
- Sponsor
- Investigators
- Fermín Sánchez-Guijo, Principal investigator, IBSAL - University Hospital of Salamanca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05086939
- Sponsor's protocol ID
- ARTROCELL
- Other IDs
- 2019-002446-21, 2024-514545-11-00, 2019
- Acronym
- ARTROCELL
- Status last verified
- Nov 2024
- First submitted
- 5 Jul 2021
- Last updated
- 29 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05086939
- Acronym / sponsor ID
- ARTROCELL / ARTROCELL
- Conditions
- Knee Osteoarthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y LeónUniversity, hospital or other
- Collaborators
- Instituto de Investigación Biomédica de Salamanca, Spanish Clinical Research Network - SCReN, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Universitari de Bellvitge
- Study start
- 26 May 2021 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 21 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Randomized, Open-label, Clinical Trial comparing 3 active treatments.
| Arm | Type | Receives |
|---|---|---|
| Autologous Mesenchymal Stromal Cells (MSC) | Experimental | Drug: Autologous MSCsTreatment with 40 millions of autologous autologous adult mesenchymal stem cells from expanded bone marrow administered intra-articularly. |
| Allogenic Mesenchymal Stromal Cells (MSC) | Experimental | Drug: Allogenic MSCsTreatment with 40 millions of adult allogeneic expanded bone marrow mesenchymal stem cells administered intra-articularly. |
| Active Control | Active comparator | Drug: Hyaluronic AcidHyaluronic Acid 60mg/3ml administered intra-articularly. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous MSCsIntra-articular injection 40 million/4 ml. | Drug | Autologous Mesenchymal Stromal Cells (MSC) |
| Allogenic MSCsIntra-articular injection 40 million/4 ml. | Drug | Allogenic Mesenchymal Stromal Cells (MSC) |
| Hyaluronic AcidAlso: Hyaluronic Acid 20 mg/mlIntra-articular injection 60mg / 3 ml . | Drug | Active Control |
Primary outcome
Range of motion.
Time frame: 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.
Time frame: 12 months
Evaluation of pain using Visual Analogue Scale (VAS) (Pain self-assessment score range from 0 -no pain- to 10 -maximum-).
Knee Osteoarthritis.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Radiological response using nuclear magnetic resonance imaging.
Time frame: 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).
5 secondary outcomes
Perceived general well-being.
Time frame: 6, 12 and 24 months
Feasibility assessment of a multicentre strategy production of both cell types with several Cell Production Units
Time frame: 24 months
Evaluation of presence of adverse events related with investigational medical product (IMP).
Time frame: 24 months
Evaluation of products obtained by genomic study and potency studies of the final products of all cell types (exploratory objective)
Time frame: 30 days
Evaluate induced changes in circulating cells of the immune system after cell treatment (exploratory objetive)
Time frame: 30 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fermín Sánchez-Guijo principal investigator
IBSAL - University Hospital of Salamanca
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Autologous MSCs, Allogenic MSCs and Hyaluronic Acid in people with Knee Osteoarthritis, run by Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León at 8 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Range of motion. (time frame: 12 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.