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Osteoarthritis Cartilage. 2015 Dec;23(12):2109-2118. doi: 10.1016/j.joca.2015.06.019. Epub 2015 Jul 16.

Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenerative joint disease of the knee.

Author information

1
Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA.
2
Rothman Institute, Thomas Jefferson University, 925 Chestnut St 5th Fl, Philadelphia, PA 19107, USA.
3
Pinellas Park, 4820 Park Blvd., Pinellas Park, FL 33781, USA.
4
TissueGene, Inc., 9605 Medical Center Drive, Suite 200, Rockville, MD 20850, USA.
5
Commonwealth Orthopaedics, 1635 N George Mason Dr Ste 310, Arlington, VA 22205-3616, USA.
6
Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA. Electronic address: mmont@lifebridgehealth.org.

Abstract

OBJECTIVE:

The aim of this study was to preliminarily evaluate the efficacy and outcomes of injectable genetically engineered chondrocytes virally transduced with TGF-β1 (GEC-TGF-β1) compared to placebo.

DESIGN:

A multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 2:1 randomized to GEC-TGF-β1 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-β1 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-β1 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-β1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed.

CONCLUSIONS:

GEC-TGF-β1 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".

KEYWORDS:

Genetically modified; Growth factors; Knee; Osteoarthritis; Pain; TissueGene

PMID:
26188189
DOI:
10.1016/j.joca.2015.06.019
[Indexed for MEDLINE]
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