A Randomized Clinical Trial to Evaluate Two Doses of an Intra-Articular Injection of LMWF-5A in Adults with Pain Due to Osteoarthritis of the Knee

Abstract

ObjectiveThe Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis.MethodsThis was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs).ResultsA total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (−0.93 vs −0.72; estimated difference from control: −0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was −0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%).ConclusionsThis clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee.Trial RegistrationClinicalTrials.gov NCT01839331

Use of Saline as a Placebo in Intra-articular Injections in Osteoarthritis: Potential Contributions to Nociceptive Pain Relief

“…If this effect were uniform for all OA patients, a simple subtraction might be considered the appropriate manner of dealing with this confounding factor. This appears not to be the case, as demonstrated in the clinical trial testing IA injections of the low molecular weight fraction of human serum albumin for OA [4, 5]. In this study the amelioration of pain with physiological saline was much less pronounced in patients with the most severe OA (KL 4 patients).…”

“…In recent years, intra-articular (IA) knee joint injections have been used to relieve symptoms of this condition. These have succeeded to varying degrees either with sodium hyaluronate preparations [1, 2], platelet-rich plasma (PRP) [3], or with a low molecular weight fraction (< 5kDa) of human serum albumin (LMWF-5A) [4, 5]. In all of these studies, the control arm was injection of the same volume of sterile physiological saline ( i.e .…”

“…Moreover, OAK is a variable disease, with severity measured on the Kellgren and Lawrence scale, on which KL 0 indicates no disease and KL 1 to 4 indicates arthritic changes of increasing severity. It is thought that the various hyaluronate preparations have a therapeutic effect mostly on KL 2-3 patients, whereas the LMWF-5A preparation works best on KL 3-4 patients [1, 4, 5]. Since the effect of saline injection is always greater than no treatment, evaluations of these treatments can be confounded in clinical trials.…”

Low Molecular Weight Fraction of Commercial Human Serum Albumin Induces Morphologic and Transcriptional Changes of Bone Marrow-Derived Mesenchymal Stem Cells

“…The safety and efficacy of LMWF5A was evaluated in 329 patients with moderate to severe OA of the knee in the multicenter, randomized, vehicle-controlled, double-blind, phase III SPRING study (ClinicalTrials.gov identifier NCT01839331) [8]. The protocol for the SPRING study was approved by the institutional review boards from SUNY-Buffalo Health Sciences and Liberty IRB (Deland, FL, https://www.libertyirb.com/) and complies with the code of ethics of the World Medical Association.…”

Preliminary Trial of Intra-articular LMWF-5A for Osteoarthritis of the Knee

“…[4][5][6][7] A pivotal phase III randomized controlled trial showed that a single intraarticular injection of LMWF-5A was effective in reducing pain in adults with osteoarthritis of the knee and was safe and well tolerated. 8 This study investigated the safety and efficacy of 3 biweekly intraarticular injections of LMWF-5A in osteoarthritis of the knee.…”