"Ready-to-use" Intra-articular Formulation of Mesenchymal Stromal Cells (PANLAR-II)

Enabling Advanced Medical Therapy in the Americas: A Pilot Study to Validate a "Ready-to-use" Intra-articular Formulation of Mesenchymal Stromal Cells, Aiming Toward an Effective and Scalable Treatment for Symptomatic Knee Osteoarthritis

The goal of this clinical trial is to compare a newly developed off-the-shelf cryopreserved "ready to inject" Mesenchymal Stem Cell (MSC) product with the usual MSC preparation the investigators have used in knee osteoarthritis (OA) patients. Since usual MSC therapy requires cell manipulation in GMP (Good Manufacturing Practices)-type facilities, this new formulation would enable wider access to Cell therapy and Multicentric clinical trials in areas devoid of expensive facilities and equipment.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Biological: "Ready to inject" Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product; Biological: Resuspended Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product

Detailed Description

This is a double blind randomized controlled trial testing a modified formulation of an allogenic Umbilical cord (UC) derived MSC therapy that the investigators have used in a prior published clinical trial. It has been modified and characterized according to the standards of quality control that are required for the development an off-the-shelf cryopreserved MSCs product.

This so called "ready to inject" MSC preparation will be compared with the usual MSC formulation that requires centrifugation and resuspension in different media, thus requiring access to advanced (GMP-type) facilities.

A total of 60 symptomatic knee OA patients will be randomized (1.1 ratio) to receive one or the other MSC product at baseline and month 6, to be followed blindly for 12 months with baseline and end of study knee MRI imaging.

The primary endpoint of the trial will be the safety according to the occurrence of adverse events (AEs) as coded by the Common Terminology Criteria for Adverse Event classification. The secondary endpoint will be efficacy, as assessed by the following validated clinical outcome measures: Western Ontario and Mc Master Universities Arthritis Index (WOMAC) Spanish validated version, Pain Visual Analog scale (VAS), Quality of life by the Short-form 36 (SF-36) questionnaire, Patient Global Assessment, and the Outcome Measures in Rheumatology Committee (OMERACT)-Osteoarthritis Research Society International (OARSI) Responder Index Criteria. Baseline MRI will be performed mainly to exclude meniscal lesions associated with accelerated knee OA. Final (12 month) MRI will be performed to assess structural change in response to treatment

The completion of this project represents a main technological advance, eventually leading to the scalability and enhanced quality control of a much needed treatment, within reasonable costs and logistics, and in particular, with no need of a GMP facility at the point of care or of clinical testing

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fernando E Fernando, M.D.; Phone Number: +56 953722433; Email: ffigueroa@uandes.cl
• Study Contact Backup: Name: Francisco Espinoza, M.D.; Phone Number: +56 942201289; Email: fespinoza@clinicauandes.cl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic knee OA defined by grade 1-3 Kellgren-Lawrence radiographic changes in the targeted knee.
• Daily pain at the affected joint for at least 3 months before inclusion

Exclusion Criteria:

• Bilateral symptomatic knee OA (only if the contralateral knee has more severe disease)
• Meniscal rupture.
• Condylar or tibial plateau generalized bone marrow edema on MRI
• Major axial deviation defined by valgus (>10°) or varus (5°) deformity of the involved leg
• Use of oral or intra-articular steroids or hyaluronic acid in the past 6 months
• Ipsilateral hip or ankle pain, local or systemic infection
• Any form of secondary arthritis, previous malignancy, or body mass index ≥30.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: "Ready to inject" MSC product; Cryopreserved "ready to inject" Umbilical Cord (UC) derived MSC	Biological: "Ready to inject" Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product; Cryopreserved thaw & inject MSC intra-articular therapy; Other Names: Cryopreserved "Ready to inject" MSC product
Active Comparator: Resuspended MSC product; Umbilical Cord (UC) derived MSC in suspension media	Biological: Resuspended Umbilical cord-derived Mesenchymal Stromal Cell (MSC) product; Cryopreserved resuspended MSC intra-articular therapy; Other Names: Cryopreserved resuspended MSC product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety monitoring for Adverse events	Adverse events (AEs) reported for each study group as coded by the Common Terminology Criteria for Adverse Event classification.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC scale	Western Ontario and Mc Master Universities Arthritis Index (WOMAC) Spanish validated version. Scale ranges from 0-240 with higher scores indicating worsened state	12 months
Pain Visual Analog Scale (VAS)	VAS scale for pain, ranging from 0-10 with higher scores indicating worsened state	12 months
Quality of Life SF-36 questionnaire	Short-form 36 (SF-36) questionnaire, ranging from 0-100 with higher scores indicating better health status	12 months
Responder status	Assessed by the Outcome Measures in Rheumatology Committee (OMERACT)-Osteoarthritis Research Society International (OARSI) Responder Index Criteria. Responder status requires fulfilling at least 50% improvement in pain or function with absolute change of at least 20; or at least 20% improvemente in pain, function or patient´s global assessment, with absolute change of at least 20.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
WORMS SCORE	Baseline and 12 month MRI will be performed to assess structural change in response to treatment as computed by the Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. This score ranges 14 imaging features from 0-332 with higher scores indicating worsened state	12 months

Collaborators and Investigators

• Sponsor: Universidad de los Andes, Chile
• Collaborators: Liga Panamericana de Asociaciones de Reumatologia (PANLAR)
• Investigators: Principal Investigator: Fernando E Figueroa, M.D., Universidad De Los Andes

Publications and helpful links

General Publications

• Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, Alcayaga-Miranda F, Gonzalez PL, Muse E, Khoury M, Figueroa FE, Espinoza F. Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial. Stem Cells Transl Med. 2019 Mar;8(3):215-224. doi: 10.1002/sctm.18-0053. Epub 2018 Dec 28.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Osteoarthritis; Cell therapy; Mesenchymal Stromal Cell; Mesenchymal Stem Cell; Advanced Medicinal Therapy Product; Degenerative joint disease; Cryopreserved cell therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: PANLAR-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sharing upon request after publication of the trial.
• IPD Sharing Time Frame: At trial termination and publication.
• IPD Sharing Access Criteria: Data will be shared with researchers or scholars with no conflict of interest and once we have confirmed the data are not subject to confidentiality due to intellectual property or other issues.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No