title: Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenerative joint disease of the knee.
abstract: OBJECTIVE
  The aim of this study was to preliminarily evaluate the efficacy and outcomes of injectable genetically engineered chondrocytes virally transduced with TGF-β1 (GEC-TGF-β1) compared to placebo.
  
  
  METHODS
  A multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 2:1 randomized to GEC-TGF-β1 or placebo. Primary outcomes assessed were (1) function of the knee joint, scored using the International Knee Documentation Committee (IKDC); and (2) pain, measured by Visual Analog Scale (VAS). Secondary endpoints assessed were pain and analgesic use, quality of life (QOL), and adverse events (AEs) including need for total knee arthroplasty after treatment.
  
  
  RESULTS
  IKDC showed significant improvement in the GEC-TGF-β1 group over the placebo at week 12 (least mean square difference (LSMD): 10.3; P = 0.0342), week 52 (LSMD: 13.6; P = 0.0082), and overall (LSMD: 8.6; P = 0.0453). VAS Analysis showed a significant improvement in GEC-TGF-β1 group compared to placebo at weeks 12 (LSMD: -13.8; P = 0.0162), 52 (LSMD: -13.1; P = 0.0332), and overall (LSMD: -10.1; P = 0.0350). Reduction in pain severity at week 12 and 52, frequency at 24 h and week 52, and the percentage of patients in the GEC-TGF-β1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed.
  
  
  CONCLUSIONS
  GEC-TGF-β1 patients had more positive responses on the IKDC, VAS, and were less likely to require analgesics.
  
  
  BACKGROUND
  ClinicalTrials.gov (NCT01221441) - "Study of TG-C in Patients with Grade 3 Degenerative Joint Disease of the Knee".
authors.affiliation: Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cherian
authors.affiliation: Rothman Institute, Thomas Jefferson University, 925 Chestnut St 5th Fl, Philadelphia, PA 19107, USA.
authors.forename: J
authors.initials: J
authors.lastname: Parvizi
authors.affiliation: Pinellas Park, 4820 Park Blvd., Pinellas Park, FL 33781, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bramlet
authors.affiliation: TissueGene, Inc., 9605 Medical Center Drive, Suite 200, Rockville, MD 20850, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Commonwealth Orthopaedics, 1635 N George Mason Dr Ste 310, Arlington, VA 22205-3616, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Romness
authors.affiliation: Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA. Electronic address: mmont@lifebridgehealth.org.
authors.forename: M A
authors.initials: MA
authors.lastname: Mont
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use; D019645:Arthroplasty, Replacement, Knee / Q000706:statistics & numerical data; D017690:Cell Transplantation / Q000379:methods; D019902:Chondrocytes / Q000378:metabolism / Q000637:transplantation*; D004311:Double-Blind Method; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000503:physiopathology / Q000628:therapy*; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D059408:Pain Management; D011788:Quality of Life; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Genetically modified; Growth factors; Knee; Osteoarthritis; Pain; TissueGene