NCT05517434

Autologous BMA vs Saline and LAM + LP-PRP vs Saline Evaluations in Knee OA

Intra-Articular Autologous Bone Marrow Aspirate vs Placebo Injection and Lipoaspirate Micronized With Leukocyte-Poor Platelet Rich Plasma vs Placebo Injection Evaluations for Treatment of Knee OsteoArthritis: The ABLE OA Double-Blinded Randomized Clinical Trial

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 148 (estimated)
• Sponsor: University Health Network, Toronto · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Not accepted

Summary

ABLE OA is a Health Canada authorized (phase II/III) trial \[Parent Control #: 263591\]. 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 (BMA) injection; and, ii) combined lipoaspirate micronized (LAM) and leukocyte poor (LP) platelet-rich plasma (PRP) injections for the treatment of knee osteoarthritis (OA). BMA, LAM from lipoaspirate (LA), and LP-PRP from whole blood will be prepared using the Cervos Marrow Cellution™ Bone Marrow Aspiration System, Cervos LIPO-PRO™ Adipose Transfer System, and Cervos KEYPRP Platelet Separator System, respectively. Patient-reported outcome (PRO) 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.

Detailed description

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 BMA or LAM + 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 BMA or LAM + 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 (BMA or LAM + LP-PRP) arm to a placebo saline control arm. OTHER SECONDARY OBJECTIVES: * To evaluate if an injection of BMA or LAM + 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 BMA or LAM + 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. * To evaluate health care consumption and health-related productivity losses of paid and unpaid work using the iMTA Medical Consumption Questionnaire (iMCQ) and iMTA Productivity Cost Questionnaire (iPCQ), respectively at 6 and 12 months post-injection relative to baseline. * To determine the quality-adjusted-life years (QALYs) using the 5-level EuroQol five-dimensional (EQ-5D-5L) health state utility scores based on the Canadian preference weights to inform cost-effective estimates. 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: 1. the cellular composition and soluble factors in BMA, LAM and LP-PRP autologous cellular preparations \[in BMA or LAM + LP-PRP groups only\] 2. the levels of local and systemic immune cell and inflammatory profiles of patients (based on synovial fluid, blood, and urine readouts) \[in BMA or LAM + LP-PRP and placebo groups\] 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.

Conditions

• Osteoarthritis, Knee

Interventions

Type	Name	Description
BIOLOGICAL	Bone Marrow Aspirate (BMA): Minimally manipulated autologous cellular preparation	Participants will undergo a bone marrow aspiration. About 10 mL of BMA will be collected from the posterior iliac spine i.e., ipsilateral and/or contralateral iliac crest using the Cervos Marrow Cellution™ kit. The BMA does not require processing using a centrifuge after collection. 9 mL (or less) of BMA is injected into the osteoarthritic knee joint after collection (Arm A, Study 1).
OTHER	Saline (Placebo Comparator for BMA)	Participants will undergo a bone marrow aspiration to collect about 10 mL of BMA from the posterior iliac spine i.e., ipsilateral and/or contralateral iliac crest. However, 0.9% sodium chloride (NaCl) Baxter or equivalent (9 mL) is injected into the osteoarthritic knee joint (Arm C, Study 1).
BIOLOGICAL	Lipoaspirate Micronized + Leukocyte-Poor Platelet-Rich Plasma (LAM + LP-PRP): Minimally manipulated autologous cellular preparations	Participants will undergo a lipoaspiration. 40 mL of lipoaspirate (LA) will be collected from subcutaneous adipose tissue. LA will be processed using the Cervos LIPO-PRO™ kit and a centrifuge. Participants will also undergo a blood draw. About 30 mL of whole blood will be collected from the antecubital fossa. Whole blood will be processed using the Cervos KEYPRP kit and a centrifuge. After processing, 9 mL (or less) of LAM is injected first followed immediately by 2 mL (or less) of LP-PRP into the osteoarthritic knee joint (Arm B, Study 2).
OTHER	Saline (Placebo Comparator for LAM + LP-PRP)	Participants will undergo a lipoaspiration to collect 40 mL of LA and a blood draw to collect about 30 mL of whole blood. However, 0.9% of sodium chloride (NaCl) Baxter or equivalent is injected twice (9 mL + 2 mL) into the osteoarthritic knee joint (Arm D, Study 2).

Timeline

• Start date: 2025-01-01
• Primary completion: 2026-06-01
• Completion: 2026-12-01
• First posted: 2022-08-26
• Last updated: 2025-12-19

Locations

2 sites across 1 country: Canada