A Multicenter, Double-Blind, Phase III Clinical Trial to Evaluate the Efficacy and Safety of a Cell and Gene Therapy in Knee Osteoarthritis Patients
- 주제(키워드) TissueGene-C , osteoarthritis , gene therapy , Phase III
- 주제(기타) Biotechnology & Applied Microbiology; Critical Care Medicine; Medicine, Research & Experimental
- 설명문(일반) [Kim, Myung-Ku] Inha Univ Hosp, Incheon, South Korea; [Ha, Chul-Won] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Seoul, South Korea; [In, Yong] Catholic Univ Korea, Coll Med, Seoul, South Korea; [Cho, Sung-Do] Ulsan Univ Hosp, Ulsan, South Korea; [Bing, Seong-Il] Univ Ulsan, Asan Med Ctr, Coll Med, Ulsan, South Korea; [Choi, Eui-Sung] Chungbuk Natl Univ Hosp, Cheongju, South Korea; [Ha, Jeong-Ku] Inje Univ, Seoul Paik Hosp, Seoul, South Korea; [Lee, Ju-Hong] Jeonbuk Natl Univ, Med Sch, Jeonju, South Korea; [Yoo, Jae-Doo] Ewha Womans Univ, Mokdong Hosp, Seoul, South Korea; [Choi, Choong-Hyeok] Hanyang Univ, Coll Med, Seoul, South Korea; [Kyung, Hee-Soo] Kyungpook Natl Univ, Daegu, South Korea; [Lee, Myung-Chul] Seoul Natl Univ Hosp, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 MARY ANN LIEBERT, INC
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000151459
- 본문언어 영어
- Published As http://dx.doi.org/10.1089/humc.2017.249
초록/요약
The aim of this study was 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 transforming growth factor-1. A total of 163 Kellgren-Lawrence grade 3 patients with knee osteoarthritis were randomly assigned to receive intra-articular TG-C or placebo. 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 function by the Western Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms, daily activities, function in sports and recreation, and quality of life by the Knee Injury and Osteoarthritis Outcome Score (KOOS), X-ray, magnetic resonance imaging, and soluble urine and blood biomarkers. 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 toward 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 these were not statistically significant (p>0.05). Serum C-terminal telopeptide of type I collagen (CTX-I) and urine CTX-II levels were 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 great potential as a 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%). TG-C was associated with statistically significant improvements in function and pain in patients with knee osteoarthritis. The unexpected adverse events were not observed.
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