Intra-articular Injection of UC-MSC Exosome in Knee Osteoarthritis

Osteo Arthritis Knee Clinical Trial

— EXO-OA01  

Official title:

Administration of sEV Derived From UC-MSC in Patients With Osteoarthritis of the Knee: Safety Determination in a Pilot Dose-escalation Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06431152
• Other study ID #: EXO-OA01
• Status: Recruiting
• Phase: Early Phase 1
• Start date: June 1, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Universidad de los Andes, Chile
• Contact: Jose Matas, MD
• Phone: +56 2 26183347
• Email: jmatas[@]clinicauandes.cl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aim to evaluate safety of exosomes (sEVs) from allogeneic mesenchymal stromal cells delivered by an intra-articular injection in the knee of patients with mild to moderate symptomatic osteoarthritis. The sEVs will be produced in a GMP-facility. The investigators expect to enroll 12 patients in this phase 1 trial open label dose-escalation pilot and the follow-up will be up to 12 months.

Description:

The clinical investigation will represent a Phase 1 trial focusing on small extracellular vesicles derived from mesenchymal stem cell (MSC-sEV) in patients with symptomatic Kellgren II-III knee OA. The phase 1 component of the study will be an open-label dose escalation pilot study in which three cohorts of subjects with OA will receive increasing doses of UC-MSC-sEV administered as a single intra-articular (IA) injection. Each cohort will comprise four participants. Eligible study subjects will be enrolled at the "Clinica Universidad de los Andes".

The small extracellular vesicles derived from umbilical cord mesenchymal stem cell (UC-MSC-sEV) will be prepared in the "Clinica Universidad de los Andes" GMP facility. The sEV-based therapeutic for clinical use will be manufactured in compliance with standardized procedures based on Good Manufacture Practice (GMP) regulations and all quality controls aforementioned. The sEV therapeutic will be transported to the patient administration site under controlled conditions, ensuring maintenance of a temperature range between 2-8°C. The sEV injection is expected to be administered within the first 6 h of product manufacture.

The primary study endpoints of this trial will focus on the safety, feasibility, and toxicity of the sEV-based product. The phase I will examine (1) the incidence of immediate post-infiltration adverse reactions in patients; (2) the occurrence of synovitis post-infiltration in patients at 24 and 48 hours, as well as on days 7 and 15; (3) the frequency of post-infiltration pain reported by patients at 24 and 48 h, and on days 7 and 15; and (4) the prevalence of adverse events related to sEV therapy occurring beyond IA infiltration at 24 and 48 h, and on days 7 and 15, as well as at months 2, 4, 6, 8, 10, and

12. The secondary study endpoint will be determine the optimal dose for phase II trials. The criteria that will be considered are (1) Safety profile at infiltration at 24 and 48 h, and on days 7 and 15, as well as at months 2, 4, 6, 8, 10, and 12; (2) changes in WOMAC scores at months 2, 4, 6, 8, 10, and 12; and (3) alterations in the Visual Analog Scale (VAS) pain scores at months 2, 4, 6, 8, 10, and 12.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age 30 to 70 years.

• Kellgren-Lawrence grade II - III knee OA (Rosenberg view x-ray)

• VAS for pain = 40 mm, without surgical indication in the affected knee.

• In case of bilateral involvement, the most affected knee will be treated. The contralateral knee should be asymptomatic or present a VAS = 20 mm.

• Stable knee with normal physical examination.

• Signed Informed Consent

Exclusion Criteria:

• Symptomatic bilateral knee OA

• BMI > 30 kg/m2

• Joint instability at physical examination.

• Mechanical meniscal tear on physical examination.

• Associated conditions: active local or systemic infection, neoplasia, immunosuppression, pregnancy, anticoagulant therapy, coagulation disorders, inflammatory joint disease (autoimmune, by crystal or other), joint prosthesis, symptomatic spine or hip disease.

• Recent use of intra-articular (last 6 months) or oral (last month) steroid therapy.

• Recent use of intra-articular hyaluronic acid therapy (last 6 months)

• Subchondral bone fracture.

Related Conditions & MeSH terms

• Osteo Arthritis Knee
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Biological:
• UC-MSC sEV
Small extracellular vesicles derived from allogenic mesenchymal stromal cells, single dose

Locations

Country	Name	City	State
Chile	Clinica Universidad de los Andes	Santiago	Las Condes

Sponsors (1)

Lead Sponsor	Collaborator
Universidad de los Andes, Chile

Country where clinical trial is conducted

Chile, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Event	Occurrence of any adverse reactions within 12 months of treatment	12 month
Secondary	Incidence of injection-related pain according to Visual Analogue Scale (VAS) (0-100mm)	Pain measured by Visual Analogue Scale (VAS) (0-100mm) after first week of treatment	1-2 weeks
Secondary	Incidence of injection-related synovitis according to effusion grading scale of knee joint	Synovitis measured by effusion grading scale (zero to 3+) after first week of treatment	1-2 weeks
Secondary	Pain change	Change in Visual Analogue Scale (VAS) (0-100mm) score every 2 months	12 months
Secondary	Disability change	Change in WOMAC subscale (Western Ontario and McMaster Universities Osteoarthritis IndexWomac) related to function (C) every 2 months Pain (0-20), Stiffness (0-8), functional capacity (0-68).	12 months
Secondary	Percentage of responders	According to OMERACT-OARSI Criteria Index Response after 52 weeks	52 weeks