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Hum Gene Ther Clin Dev. 2018 Mar;29(1):48-59. doi: 10.1089/humc.2017.249.

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

Author information

1
1 Inha University Hospital , Incheon, South Korea .
2
2 Samsung Medical Center, Sung Kyun Kwan University School of Medicine , Seoul, South Korea .
3
3 The Catholic University of Korea College of Medicine , Seoul, South Korea .
4
4 Ulsan University Hospital, University of Ulsan College of Medicine , Ulsan, South Korea .
5
5 Chungbuk National University Hospital , Cheongju, South Korea .
6
6 Seoul Paik Hospital, Inje University , Seoul, South Korea .
7
7 Jeonbuk National University Medical School , Jeonju, South Korea .
8
8 Ewha Womans University Mokdong Hospital , Seoul, South Korea .
9
9 Asan Medical Center, University of Ulsan College of Medicine , Ulsan, South Korea .
10
10 College of Medicine, Hanyang University , Seoul, South Korea .
11
11 Kyungpook National University , Daegu, South Korea .
12
12 Seoul National University Hospital , Seoul, South Korea .

Abstract

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-β1. 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02072070.

KEYWORDS:

Phase III; TissueGene-C; gene therapy; osteoarthritis

PMID:
29641281
DOI:
10.1089/humc.2017.249
[Indexed for MEDLINE]

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