Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-ß1 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-ß1 (GEC-TGF-ß1) compared to placebo. DESIGN: A multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 21 randomized to GEC-TGF-ß1 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-ß1 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-ß1 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-ß1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed. CONCLUSIONS: GEC-TGF-ß1 patients had more positive responses on the IKDC, VAS, and were less likely to require analgesics. TRIAL NUMBER ClinicalTrials.gov (NCT01221441) - "Study of TG-C in Patients with Grade 3 Degenerative Joint Disease of the Knee".