PMID- 24498399 OWN - NLM STAT- MEDLINE DCOM- 20141020 LR - 20240314 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 2 DP - 2014 TI - 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. PG - e87910 LID - 10.1371/journal.pone.0087910 [doi] LID - e87910 AB - OBJECTIVE: The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis. METHODS: This 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 1ratio1ratio1ratio1 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). RESULTS: A 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%). CONCLUSIONS: This 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 REGISTRATION: ClinicalTrials.gov NCT01839331. FAU - Bar-Or, David AU - Bar-Or D AD - Trauma Research Department, Swedish Medical Center, Englewood, Colorado, United States of America ; Trauma Research Department, St Anthony Hospital, Lakewood, Colorado, United States of America ; Ampio Pharmaceuticals, Inc., Greenwood Village, Colorado, United States of America ; Rocky Vista University, Aurora Colorado, United States of America. FAU - Salottolo, Kristin M AU - Salottolo KM AD - Trauma Research Department, Swedish Medical Center, Englewood, Colorado, United States of America ; Trauma Research Department, St Anthony Hospital, Lakewood, Colorado, United States of America ; Ampio Pharmaceuticals, Inc., Greenwood Village, Colorado, United States of America. FAU - Loose, Holli AU - Loose H AD - Ampio Pharmaceuticals, Inc., Greenwood Village, Colorado, United States of America. FAU - Phillips, Matthew J AU - Phillips MJ AD - University Orthopaedic Center, Amherst, New York, United States of America. FAU - McGrath, Brian AU - McGrath B AD - University Orthopaedic Center, Amherst, New York, United States of America. FAU - Wei, Nathan AU - Wei N AD - Arthritis Treatment Center, Frederick Maryland, United States of America. FAU - Borders, James L AU - Borders JL AD - Central Kentucky Research Associates, Lexington, Kentucky, United States of America. FAU - Ervin, John E AU - Ervin JE AD - Center for Pharmaceutical Research, Kansas City, Missouri, United States of America. FAU - Kivitz, Alan AU - Kivitz A AD - Altoona Center for Clinical Research, Duncansville, Pennsylvania, United States of America. FAU - Hermann, Mark AU - Hermann M AD - Danville Orthopeadic Clinic, Danville Virginia, United States of America. FAU - Shlotzhauer, Tammi AU - Shlotzhauer T AD - Rochester Medical Research, Rochester, New York, United States of America. FAU - Churchill, Melvin AU - Churchill M AD - Physician Research Collaboration, Lincoln Nebraska, United States of America. FAU - Slappey, Donald AU - Slappey D AD - Alabama Clinical Therapeutics, LLC, Birmingham, Alabama, United States of America. FAU - Clift, Vaughan AU - Clift V AD - Ampio Pharmaceuticals, Inc., Greenwood Village, Colorado, United States of America. LA - eng SI - ClinicalTrials.gov/NCT01839331 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140203 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Serum Albumin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Double-Blind Method MH - Female MH - Humans MH - Injections, Intra-Articular MH - Male MH - Middle Aged MH - Molecular Weight MH - Osteoarthritis, Knee/*complications MH - Pain/*drug therapy/etiology MH - Serum Albumin/*administration & dosage MH - Severity of Illness Index MH - Treatment Outcome PMC - PMC3912151 COIS- Competing Interests: The authors have the following interests: Financial support for this study was provided by Ampio Pharmaceuticals, Inc., the employer of David Bar-Or, Kristin M. Salottolo, Vaughan Clift and Holli Loose who have stock/stock options in the company. David Bar-Or is also a board member, and inventor of patents (not paid) at Ampio Pharmaceuticals, Inc. Brian McGrath and Matthew Phillips have stock/stock options in the company. Ampion (LMWF-5A) is a product of Ampio Pharmaceuticals. There are no marketed products related to this work. There are several patents and products in development related to this work. Please see the supporting information file for more details. Donald Slappey is an employee of Alabama Clinical Therapeutics, LLC. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. EDAT- 2014/02/06 06:00 MHDA- 2014/10/21 06:00 PMCR- 2014/02/03 CRDT- 2014/02/06 06:00 PHST- 2013/10/15 00:00 [received] PHST- 2013/12/21 00:00 [accepted] PHST- 2014/02/06 06:00 [entrez] PHST- 2014/02/06 06:00 [pubmed] PHST- 2014/10/21 06:00 [medline] PHST- 2014/02/03 00:00 [pmc-release] AID - PONE-D-13-44034 [pii] AID - 10.1371/journal.pone.0087910 [doi] PST - epublish SO - PLoS One. 2014 Feb 3;9(2):e87910. doi: 10.1371/journal.pone.0087910. eCollection 2014.