Phase III, multicentre, randomized, open clinical trial comparing treatment with allogenic mesenchymal cells against autologous mesenchymal cells and against active control with hyaluronic acid in patients with knee osteoarthritis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion De Investigacion Biomedica De Salamanca

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

26 May 2021 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III

External identifiers

EU CT number

2024-514545-11-00

EudraCT number

2019-002446-21

ClinicalTrials.gov

NCT05086939

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To compare the efficacy of allogeneic mesenchymal stem cells (MSC) and autologous MSC versus an active control with hyaluronic acid in terms of clinical, functional and radiological response.

Secondary objectives 5

1. To analyse changes in the quality of life of the patients included in each of the three experimental groups.
2. To confirm the feasibility of treatment with both cell types in a multicentre strategy that includes several Cell Production Units, analysing the rate of non-compliant products with release criteria and the characteristics of the released and infused product.
3. Collect the rate of adverse effects and other pharmacovigilance parameters from the three treatment arms.
4. Evaluation of the products obtained by genomic studies and potency studies of the final products of all cell types (exploratory objective).
5. To assess the changes induced in circulating cells of the immune system after cell treatment (exploratory objective).

Conditions and MedDRA coding

Knee osteoarthritis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Kellgren and Lawrence grade 2, 3 or 4 gonarthrosis.
2. Chronic painful knee with mechanical features.
3. Absence of local or systemic septic process.
4. Haemacytometric and biochemical analyses without significant alterations contraindicating treatment.
5. Written informed consent obtained from the patient.
6. The patient is able to understand the nature of the study.
7. Body Mass Index between 20 and 35 kg/m2.

Exclusion criteria 9

1. Patient < 18 years old, or legally dependent.
2. Patient > 75 years old.
3. Congenital or evolutive diseases that result in malformation and/or significant deformities of the knee (varus<10º; valgus<20º) and cause difficulties in the application and evaluation of the results.
4. Pregnant or breastfeeding women.
5. Neoplastic disease
6. Intra-articular infiltration of any drug within 3 months prior to inclusion in the study.
7. Concurrent participation in another clinical trial or treatment with another investigational product in the 30 days prior to inclusion in the study.
8. Allergy to gentamicin (antibiotic used in the cell culture process).
9. Other illnesses or circumstances that might compromise the patient participation in the study according to medical criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Measurement of pain intensity according to the VAS pain scale at 12 months.
2. Assessment of functional capacity and pain according to the Lequesne scale at 12 months
3. Measurement of symptomatology and perceived physical disability according to the WOMAC scale at 12 months.
4. Estimation of lesion improvement or stabilisation on T2-mapping MR images at 12 months.

Secondary endpoints 6

1. Assessment of perceived quality of life on the SF-12 scale at 6, 12 and 24 months.
2. Rate of products not complying with the validation criteria in each experimental treatment branch.
3. Rate of autologous products that could not be manufactured due to alterations in the serological profile of the patients.
4. Rate of medication-related adverse effects in each of the treatment arms.
5. Cell product studies. In this exploratory objective, genomic studies will be performed by 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 response, but they are not included in the explicit secondary variables, because they will also require subsequent validation.
6. Biological studies to evaluate the immune system in the patient's blood and serum (days +7 and +30) As these are exploratory objectives, statistical analyses of correlations between the results of the biological variables and the clinical parameters will be carried out, but they are not included among the explicit secondary variables, because they will also require subsequent validation.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion De Investigacion Biomedica De Salamanca

Sponsor organisation

Fundacion De Investigacion Biomedica De Salamanca

Address

Paseo De San Vicente 58-182

City

Salamanca

Postcode

37007

Country

Spain

Scientific contact point

Organisation

Fundacion De Investigacion Biomedica De Salamanca

Contact name

Esperanza Lopez Franco

Public contact point

Organisation

Fundacion De Investigacion Biomedica De Salamanca

Contact name

Esperanza Lopez Franco

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications