Trial interventions will occur in two independent studies under a single protocol where each experimental treatment will be compared to a placebo control.~Our primary hypothesis is that BMAC or LAC + LP-PRP injection is 35% more effective than placebo saline injection control in terms of response rates in Numeric Pain Rating Scale (NPRS) scores as measured by their difference.~PRIMARY OBJECTIVE:~To determine the efficacy of an intra-articular injection of BMAC or LAC + LP-PRP in patients with knee OA by comparing each of the two treatments to a placebo saline injection control arm. Efficacy will be measured by a pain intensity improvement of a minimum of 2 points in NPRS scores at 6 months after injection relative to baseline. The study endpoint is 6 months post-injection.~KEY SECONDARY OBJECTIVE:~To determine efficacy measured by improvements in the Knee Injury and Osteoarthritis Outcome Score (KOOS) function activities of daily living (ADL) subscale scores at 6 months after injection relative to baseline by comparing each of the treatment (BMAC or LAC + LP-PRP) arm to a placebo saline control arm.~OTHER SECONDARY OBJECTIVES:~To evaluate if an injection of BMAC or LAC + LP-PRP into the knee joint shows greater improvements in other pain outcomes (including KOOS pain) compared to placebo injection at 3, 6 and 12 months post-injection relative to baseline.~To evaluate the safety of BMAC or LAC + LP-PRP injection into the knee joint compared to placebo injection. Adverse events will be collected at baseline, 3, 6 and 12 months post-injection, and deleterious effects on the joint will be assessed by X-ray at 6 months post-injection only.~To evaluate the health profile and overall self-rated health status of patients in treatment and placebo arms at 3, 6 and 12 months post-injection relative to baseline.~To evaluate overall patient satisfaction in treatment and placebo arms at 6 months post-injection.~EXPLORATORY OBJECTIVES:~To determine the correlation between changes in NPRS/KOOS pain scores and KOOS ADL function at 6 months relative to baseline and the heterogeneity in:~the cellular composition and soluble factors in BMAC, LAC and PRP autologous cellular preparations [in BMAC or LAC + LP-PRP groups only]~the levels of local and systemic immune cell and inflammatory profiles of patients (based on synovial fluid, blood, and urine readouts) [in BMAC or LAC + LP-PRP and placebo groups]~A total of approximately 84 eligible participants in each study will be randomized in a 1:1 ratio, which allows for 42 participants per group (treatment vs. placebo). This sample size considers a potential drop-out rate of 10% for each study. Three recruitment centres (Toronto Western Hospital (TWH), University Health Network (UHN); Women's College Hospital (WCH); Cleveland Clinic Canada (CCC)) and one treatment centre (TWH, UHN) will be involved in these two studies. Stratification will occur by centre, baseline NPRS of 4-6 (moderate pain) or 7-10 (severe pain), and KL grade of 2 (minimal OA) or 3 (moderate OA). Additionally, the need to re-estimate the required sample size will be evaluated using the information available at interim. At the interim analysis, contingent on observed response rates and corresponding statistical signal, the required sample size may increase, ranging from 100 to 288 patients in total for each of the two studies.
ABLE OA is a Health Canada authorized (phase II/III) trial [Control #: 263591]. A multi-center, prospective, double-blinded, randomized, placebo-controlled adaptive trial to evaluate the efficacy of two minimally manipulated autologous cellular preparations i) bone marrow aspirate concentrate (BMAC) injection; and, ii) combined lipoaspirate concentrate (LAC) and leukocyte poor (LP) platelet-rich plasma (PRP) injections for the treatment of knee osteoarthritis (OA).~BMAC, LAC, and LP-PRP will be processed using the Terumo Blood and Cell Technologies (BCT) SmartPrep® System, a functionally closed system for the clinical preparation of cellular concentrates.~Patient-reported outcome measures will be collected using web- or paper-based questionnaires administered at baseline (pre-injection) as well as at 3, 6 and 12 months (post-injection). Blood, synovial fluid, and urine samples will be collected at baseline pre-injection and 6 months post-injection only.