Schroeder Orthopaedic Advanced Therapeutics Centre

• Integration of clinical, education and research excellence to deliver exemplary patient experience and value-based healthcare.
• Develop algorithms to standardize patient intake, assessment and allocation to orthobiologic treatment in a standardized manner.
• Collect outcomes in a standardized manner.
• Using AI, assess patient data to improve patient outcomes and create personalized tailored healthcare delivery.

Developing a biosignature that correlates with response to approved anti-inflammatory therapies.

Overview

This is a planned research cohort study involving 400 patients and 1,600 patient visits over a three-year study. Patients will receive one of four Health Canada-approved orthobiologics (corticosteroid, hyaluronic acid, platelet-rich plasma or autologous protein solution).

Rationale

Pain treatment options in osteoarthritis (OA) have changed little over the years and significant challenges remain in effective symptomatic treatment of OA. Anti-inflammatory knee injections have become a treatment option and increasingly patients are inquiring about and requesting such injections.

However, treatment response is variable, and it is unclear who responds and does not respond to current intra-articular injections. Options of injections, as well as costs, continue to increase due to uncertainty in response; many approved injectates are not covered by public or private insurance and therefore present a significant clinical and economic challenge to patients and their providers with regard to one choosing the right patient for an injection and two the best injection for that patient.

Objectives

The main goal of our study is to determine:

1. Who responds or does not respond to intra-articular anti-inflammatory injections
2. Why they respond the way they do

Our ultimate aim is to be able to predict patient response prior to injection and be able to develop and provide the right therapeutic to the right patient, at the right time, and at the right value.

Hypothesis

Levels of baseline inflammation correlate with patient response to anti-inflammatory therapies. We further hypothesize that regional levels of inflammation are more correlative than systemic inflammation based on a cohort study we completed that shows strong inverse correlation of patient-reported outcome measures (PROMS) in knee OA patients with regional but not systemic levels of immune cells (Gómez-Aristizábal et al. 2019), and this is supported by other studies in the literature as well.

Stay tuned for enrollment into this cohort study.

Main objective

This study will determine the efficacy of intra-articular injection of bone marrow aspirate concentrate (BMAC) or autologous lipoaspirate with platelet-rich plasma (PRP) against PRP in patients with knee or shoulder osteoarthritis. Efficacy will be measured as improvement in pain at 12 months after injection, relative to baseline and will be compared against PRP response rates. Dropout/failure rate (based on the provided definition) will also be assessed in each group over the 12-month period, specifically at 3, 6 and 12 months.

Secondarily functional joint-specific outcomes will be measured after BMAC, LA +PRP or PRP injections at baseline, 3, 6 and 12 months. Heterogeneity in the cellular composition of BMA and LA will be assessed. As in the LEAP in BIO cohort study, heterogeneity in local and systemic immune cell profile and inflammatory profile will also be assessed.

Exploratory objectives

AI approaches will be used to identify unique inflammatory, immune cell profiles agnostic to response status to determine whether these unbiased profiles correlate to or accurately predict response or in combination with other factors enhance our ability to predict response compared to clinically biased profiles. Health economics of receiving the different injections and the cost of health care delivery will also be compared, post hoc.

Stay tuned for updates on the start and enrollment into this study.

We plan to conduct a bridging Health Canada-authorized clinical trial on 40 knee OA patients using allogeneic adipose tissue-derived mesenchymal stromal cells (AD-MSCs). This trial is a bridge between our previously conducted autologous bone marrow-derived MSCs (Chahal et al. 2019) and autologous AD-MSCs trial conducted by collaborators in Europe (Pers et al., 2017). The bridging trial will assess safety and efficacy relative to baseline at 3, 6, 12 and 24 months using Knee Outcome and Osteoarthritis Scores (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as PROMS, x-ray and MRI imaging and evaluation of local immune cell profile (synovial fluid at baseline and 3 months post-injection) and systemic inflammatory profile.

As a first step in this project, bioreactor(s) to scale up and produce Master Cell Banks (MCB) of allogenic AD-MSCs will be evaluated for MSC yield, potency, ease of use, cost and regulatory support. Data from these engineering runs will be used to support the regulatory Clinical Trial Application (CTA) filing.

First step = scaling up production of AD-MSCs

This last pillar is focused on forward-looking therapies being developed in the research lab of Dr. Viswanathan. We are looking at several next-generation technologies in the pipeline including genetically engineered allogeneic MSCs, induced pluripotent stem cell (iPSC)-derived MSCs, and iPSC-derived and genetically engineered monocyte/macrophages, 3D printed synovial tissue/MSC-differentiated chondrocytes, etc.

These are largely research-stage projects involving laboratory proof-of-concept experiments and animal studies and will pave the way for next-generation of OA cellular therapeutics which can be translated into the clinic.

A strong research arm will ensure a pipeline of new and emerging technologies that can be translated into clinical practice using the know-how we obtain from the other pillars, especially in terms of targeting appropriate patients and matching them with the most effective anti-inflammatory treatments.