PMID- 30609439 OWN - NLM STAT- MEDLINE DCOM- 20200812 LR - 20200812 IS - 1938-2480 (Electronic) IS - 1538-8506 (Linking) VI - 33 IP - 2 DP - 2020 Feb TI - Results of a Phase II Study to Determine the Efficacy and Safety of Genetically Engineered Allogeneic Human Chondrocytes Expressing TGF-beta1. PG - 167-172 LID - 10.1055/s-0038-1676803 [doi] AB - Genetically engineered chondrocytes virally transduced with a transforming growth factor (TGF)-beta1 (TG-C [TissueGene-C]) expression vector have been shown to have potential benefits in the nonoperative management of knee osteoarthritis. Previous literature has reported on safe dosages of TG-C. Therefore, the purpose of this study was to evaluate the Phase II results and a 24-month efficacy of this injectable mixture compared with placebo in patients with Kellgren-Lawrence (K-L) grade III knee osteoarthritis. Specifically, we assessed (1) functional outcomes, (2) pain scores, (3) adverse events (AEs), and (4) magnetic resonance imaging (MRIs) findings. We performed a multicenter, double-blinded, placebo-controlled, and randomized study of adults who had K-L grade III knee osteoarthritis. A total of 102 patients were 2:1 randomized to TG-C at a dose of 3.0 x 10(7) cells, or placebo injections between May 1, 2011 and October 31, 2012. Outcomes analyzed were knee joint function, pain, quality of life, adverse events, and MRI findings using the whole-organ magnetic resonance imaging score (WORMS) system. There were significant improvements in the International Knee Documentation Committee (IKDC) and visual analogue scale (VAS) scores in the TG-C cohort, when compared with the placebo cohort at weeks 12, 52, 72, and 104 (p < 0.05). No severe AEs were observed. Common AEs were arthralgia, joint inflammation, and joint effusion which were similar between both cohorts. Whole-knee MRIs at 12 months showed less progression of cartilage damage, infrapatellar fat pad-synovitis, and effusion-synovitis in the TG-C cohort. Patients who received TG-C had significant improvements in IKDC and VAS scores. These patients also reported less severe and frequent pain. Additionally, fewer patients treated with TG-C showed progression of cartilage damage, as well as less progression of infrapatellar fat pad synovitis and effusion-synovitis. Furthermore, treatment with TG-C was generally well tolerated with minor AEs. Therefore, based on these results, TG-C appears to be a safe and effective modality for the management of K-L grade III osteoarthritis. CI - Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA. FAU - Lee, Bumsup AU - Lee B AD - Kolon Life Science, Inc., Gwacheon, Gyeonggi, Republic of Korea. FAU - Parvizi, Javad AU - Parvizi J AD - Rothman Institute Philadelphia, Pennsylvania. FAU - Bramlet, Dale AU - Bramlet D AD - Department of Orthopaedic Surgery, Pinellas Park, Pinellas Park, Florida. FAU - Romness, David W AU - Romness DW AD - Department of Orthopaedic Surgery, OrthoVirginia, Arlington, Virginia. FAU - Guermazi, Ali AU - Guermazi A AD - Quantitative Imaging Center, Boston University School of Medicine, Boston, Massachusetts. FAU - Noh, Moon AU - Noh M AD - Kolon Life Science, Inc., Gwacheon, Gyeonggi, Republic of Korea. FAU - Sodhi, Nipun AU - Sodhi N AD - Department of Orthopaedic Surgery, Lenox Hill Hospital, Northwell Health, New York, New York. FAU - Khlopas, Anton AU - Khlopas A AD - Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio. FAU - Mont, Michael A AU - Mont MA AD - Department of Orthopaedic Surgery, Lenox Hill Hospital, Northwell Health, New York, New York. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20190104 PL - Germany TA - J Knee Surg JT - The journal of knee surgery JID - 101137599 RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Adult MH - Aged MH - Cell Transplantation/*methods MH - Chondrocytes/*metabolism/*transplantation MH - Double-Blind Method MH - Female MH - Genetic Engineering MH - Humans MH - Injections, Intra-Articular MH - Knee Joint/diagnostic imaging/surgery MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Osteoarthritis, Knee/diagnostic imaging/*surgery MH - Transduction, Genetic MH - Transforming Growth Factor beta1/*biosynthesis/metabolism MH - Transplantation, Homologous MH - Treatment Outcome COIS- B.L.: Kolon TissueGene. J.P.: Alphaeon, CeramTec, Ceribell, ConvaTec, Corentec, Cross Current Business Intelligence, Datatrace, Eastern Orthopaedic Association, Elsevier, Ethicon, Heron, Hip Innovation Technology, Intellijoint, Invisible Sentinelp, Jaypee Publishers, Joint Purification Systems, Journal of Bone and Joint Surgery-American, MDValuate, MedAp, MicroGenDx, Muller Foundation, Parvizi Surgical Innovations, Physician Recommended Nutriceuticals, PRN-Veterinary, SLACK Incorporated, Tenor, Kolon TissueGene, Wolters Kluwer Health - Lippincott Williams & Wilkins, Zimmer. D.W.R.: AAOS, Eastern Orthopaedic Assn., Virginia Orthopaedic Society, Centrexion, Tenex, Kolon Tissuegene. A.G.: AstraZeneca, Boston Imaging Core Lab, GE Healthcare, Merck, Norvartis, OrthoTrophix, Pfizer; Kolon TissueGene. M.N.: Kolon TissueGene; M.A.M.: AAOS, Cymedica, DJ Orthopaedics, Johnson & Johnson, Journal of Arthroplasty, Journal of Knee Surgery, Microport, National Institutes of Health (NIAMS & NICHD), Ongoing Care Solutions, Orthopedics, Orthosensor, Pacira, Peerwell, Performance Dynamics Inc, Sage, Stryker: IP royalties, Surgical Technologies International, Kolon TissueGene. EDAT- 2019/01/05 06:00 MHDA- 2020/08/13 06:00 CRDT- 2019/01/05 06:00 PHST- 2019/01/05 06:00 [pubmed] PHST- 2020/08/13 06:00 [medline] PHST- 2019/01/05 06:00 [entrez] AID - 10.1055/s-0038-1676803 [doi] PST - ppublish SO - J Knee Surg. 2020 Feb;33(2):167-172. doi: 10.1055/s-0038-1676803. Epub 2019 Jan 4.