Intra-articular injection of the anti-inflammatory compound LMWF-5A in adults with severe osteoarthritis: a double-blind prospective randomized controlled multi-center safety and efficacy trial

Abstract

Background: There are limited efficacious treatment options for severe osteoarthritis of the knee (OAK). The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is in development to treat severe OAK. This study evaluated the safety and efficacy of LMWF-5A for the signs and symptoms of OAK.

Methods: This 12-week randomized, double-blind, controlled clinical trial was conducted at thirteen sites across the United States. Patients with symptomatic, severe OAK (Kellgren-Lawrence grade 4 disease) who were fully ambulatory and had no other conditions interfering with the study knee were randomized to a single 4 ml intra-articular injection of LMWF-5A or saline, randomized 6:1. The primary endpoint was Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder rate (%), examined with a one-sided exact binomial test compared to a clinically meaningful response rate of 30%. Efficacy of LMWF-5A was also evaluated as controlled responder (%), defined as 20% improvements in both pain and function, compared to historical saline control from three previous trials. Safety was examined as the incidence and severity of adverse events (AEs). This trial was registered (clinicaltrials.gov identifier: NCT03182686).

Results: In total, 168 patients were randomized; 144 subjects treated with LMWF-5A were analysed. Overall, 71% (95% CI: 63.4%-78.3%) of subjects treated with LMWF-5A met the OMERACT-OARSI responder criteria, exceeding the 30% threshold (p < 0.001). There were also significantly more responders at week 12 in the LMWF-5A arm than historical saline control (65% vs. 43%, p < 0.001). There were no drug-related serious AEs reported and no deaths or withdrawals due to adverse events.

Conclusion: LMWF-5A provides relief for the signs and symptoms of severe osteoarthritis, and may be an alternative therapeutic treatment option for patients with severe osteoarthritis of the knee.

Keywords: Efficacy; Intra-articular injection; Osteoarthritis; Safety.

Conflict of interest statement

The study was approved from the Schulman Institutional Review Board with documentation of informed consent. Dr. Bar-Or reports personal fees from Ampio Pharmaceuticals Inc., during the conduct of the study; In addition, Dr. Bar-Or has 120 issued patents and 80 pending. Dr. Bar-Or is an employee of Ampio Pharmaceuticals, Inc. and serves as the chief Scientific officer of Ampio Pharmaceuticals and own stocks and stock options in the company. Ampio is developing LMWF-5A for the treatment of OA of the knee. Mrs. Salottolo reports personal fees from Ampio Pharmaceuticals, Inc., and own stocks and stock options in the company. Dr. Cole reports conflicts outside the submitted work including: personal fees and other from Arthrex, other from Arthroscopy; other from Aesculap/B.Braun, other from American Journal of Orthopedics, other from American Orthopaedic Society for Sports Medicine, other from American Shoulder and Elbow Surgeons, personal fees and other from Arthrex, Inc., other from Arthroscopy Association of North America, other from Athletico, other from Carticept, other from Cytori, other from DJ Orthopaedics, other from Elsevier Publishing, other from International Cartilage Repair Society, other from Journal of Bone & Joint Surgery - American, other from Journal of Shoulder and Elbow Surgery, other from Journal of the American Academy of Orthopaedic Surgeons, other from Medipost, other from National Institutes of Health (NIAMS & NICHD), other from Ossur, personal fees and other from Regentis, other from Saunders/Mosby-Elsevier, other from Smith & Nephew, other from Tornier, personal fees and other from Zimmer, other from Arthroscopy.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

CONSORT flowchart