Intra-articular Injection of UC-MSC Exosome in Knee Osteoarthritis (EXO-OA01)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Biological: UC-MSC sEV

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jose Matas, MD; Phone Number: 3347 +56 2 26183347; Email: jmatas@clinicauandes.cl
• Study Contact Backup: Name: Francisco Espinoza, MD; Phone Number: 3347 +56 2 26183347; Email: fespinoza@clinicauandes.cl

Study Locations

• Chile
  • Las Condes
    • Santiago, Las Condes, Chile, 2501
      • Recruiting
      • Clínica Universidad de los Andes
      • Contact: Bernardita Hurtado; Phone Number: 226182071; Email: bhurtadodeme@clinicauandes.cl
      • Contact: Consuelo Covarrubias; Phone Number: 226182071; Email: ccovarrubias@uandes.cl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Dose; Intra-articular knee injection of exosomes (2 x 10e9 particles/dose) derived from allogeneic mesenchymal stromal cells. Single dose. 4 patients	Biological: UC-MSC sEV; Small extracellular vesicles derived from allogenic mesenchymal stromal cells, single dose; Other Names: Cellistem®sEV-OA
Experimental: Medial-Dose; Intra-articular knee injection of exosomes (6 x 10e9 particles/dose) derived from allogeneic mesenchymal stromal cells. Single dose. 4 patients	Biological: UC-MSC sEV; Small extracellular vesicles derived from allogenic mesenchymal stromal cells, single dose; Other Names: Cellistem®sEV-OA
Experimental: High-Dose; Intra-articular knee injection of exosomes (2 x 10e10 particles/dose) derived from allogeneic mesenchymal stromal cells. Single dose. 4 patients	Biological: UC-MSC sEV; Small extracellular vesicles derived from allogenic mesenchymal stromal cells, single dose; Other Names: Cellistem®sEV-OA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event	Occurrence of any adverse reactions within 12 months of treatment	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of responders	According to OMERACT-OARSI Criteria Index Response after 52 weeks	52 weeks
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
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
Pain change	Change in Visual Analogue Scale (VAS) (0-100mm) score every 2 months	12 months
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

Collaborators and Investigators

• Sponsor: Universidad de los Andes, Chile

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 17, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 27, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: EXO-OA01

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