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.