A Multicenter, Double-Blind, Phase III Clinical Trial to Evaluate the Efficacy and Safety of a Cell and Gene Therapy in Knee Osteoarthritis Patients.

Abstract

OBJECTIVE To test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1), retrovirally transduced to overexpress TGF-β1. DESIGN We randomly assigned 163 with knee osteoarthritis to receive intra-articular TG-C or placebo in Kellgren-Lawrence grade 3 patients for clinical trial. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks. Secondary efficacy measures included IKDC and VAS at 26 and 39 weeks; pain, stiffness, and physical functions by the Western Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms, daily activities, functions in sports and recreation, and quality of life by the Knee Injury and Osteoarthritis Outcome Score (KOOS), X ray, MRI, and soluble urine and blood biomarkers. RESULTS TG-C was associated with statistically significant improvement over placebo in the total IKDC score and individual categories, and in the VAS score at 26, 39, and 52 weeks. WOMAC and KOOS scores also improved with TG-C over placebo. Patients treated with TG-C showed trends directed towards thicker cartilage and slower growing rates of subchondral bone surface area in the medial tibia, lateral tibia, lateral patella, and lateral patella femoral regions, although not statistically significant (P > 0.05). Serum CTX-I and urine CTX II levels showed lower over 1 year in TG-C than placebo treated patients with CTX-I level reaching statistical significance. These tendencies supported TG-C as holding a great potential for disease-modifying osteoarthritis drug. The most frequent adverse events in the TG-C group were peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%). CONCLUSIONS TG-C was associated with statistically significant improvements in functions and pain in patients with knee osteoarthritis. The unexpected adverse events were not observed. TRIAL REGISTRATION clinicaltrials.gov NCT02072070 and CRiS: KCT0001112.