TY - JOUR
T1 - Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects
AU - Kitamura, Masahiro
AU - Akamatsu, Motoki
AU - Kawanami, Masamitsu
AU - Furuichi, Yasushi
AU - Fujii, Takeo
AU - Mori, Mari
AU - Kunimatsu, Kazushi
AU - Shimauchi, Hidetoshi
AU - Ogata, Yorimasa
AU - Yamamoto, Matsuo
AU - Nakagawa, Taneaki
AU - Sato, Shuichi
AU - Ito, Koichi
AU - Ogasawara, Takefumi
AU - Izumi, Yuichi
AU - Gomi, Kazuhiro
AU - Yamazaki, Kazuhisa
AU - Yoshie, Hiromasa
AU - Fukuda, Mitsuo
AU - Noguchi, Toshihide
AU - Takashiba, Shogo
AU - Kurihara, Hidemi
AU - Nagata, Toshihiko
AU - Hamachi, Takafumi
AU - Maeda, Katsumasa
AU - Yokota, Makoto
AU - Sakagami, Ryuji
AU - Hara, Yoshitaka
AU - Noguchi, Kazuyuki
AU - Furuuchi, Toshi
AU - Sasano, Takashi
AU - Imai, Enyu
AU - Ohmae, Masatoshi
AU - Koizumi, Hayuru
AU - Watanuki, Mitsuru
AU - Murakami, Shinya
N1 - Publisher Copyright:
© 2016 American Society for Bone and Mineral Research.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - We investigated the efficacy, safety, and clinical significance of trafermin, a recombinant human fibroblast growth factor (rhFGF)-2, for periodontal regeneration in intrabony defects in Phase III trials. Study A, a multicenter, randomized, double-blind, placebo-controlled study, was conducted at 24 centers. Patients with periodontitis with 4-mm and 3-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 328 patients were randomly assigned (2:1) to receive 0.3% rhFGF-2 or placebo, and 323 patients received the assigned investigational drug during flap surgery. One of the co-primary endpoints, the percentage of bone fill at 36 weeks after drug administration, was significantly greater in the rhFGF-2 group at 37.131% (95% confidence interval [CI], 32.7502 to 41.5123; n = 208) than it was in the placebo group at 21.579% (95% CI, 16.3571 to 26.8011; n = 100; p < 0.001). The other endpoint, the clinical attachment level regained at 36 weeks, was not significantly different between groups. Study B, a multicenter, randomized, blinded (patients and evaluators of radiographs), and active-controlled study was conducted at 15 centers to clarify the clinical significance of rhFGF-2. Patients with 6-mm and 4-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 274 patients were randomly assigned (5:5:2) to receive rhFGF-2, enamel matrix derivative (EMD), or flap surgery alone. A total of 267 patients received the assigned treatment during flap surgery. The primary endpoint, the linear alveolar bone growth at 36 weeks, was 1.927 mm (95% CI, 1.6615 to 2.1920; n = 108) in the rhFGF-2 group and 1.359 mm (95% CI, 1.0683 to 1.6495; n = 109) in the EMD group, showing non-inferiority (a prespecified margin of 0.3 mm) and superiority of rhFGF-2 to EMD. Safety problems were not identified in either study. Therefore, trafermin is an effective and safe treatment for periodontal regeneration in intrabony defect, and its efficacy was superior in rhFGF-2 compared to EMD treatments.
AB - We investigated the efficacy, safety, and clinical significance of trafermin, a recombinant human fibroblast growth factor (rhFGF)-2, for periodontal regeneration in intrabony defects in Phase III trials. Study A, a multicenter, randomized, double-blind, placebo-controlled study, was conducted at 24 centers. Patients with periodontitis with 4-mm and 3-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 328 patients were randomly assigned (2:1) to receive 0.3% rhFGF-2 or placebo, and 323 patients received the assigned investigational drug during flap surgery. One of the co-primary endpoints, the percentage of bone fill at 36 weeks after drug administration, was significantly greater in the rhFGF-2 group at 37.131% (95% confidence interval [CI], 32.7502 to 41.5123; n = 208) than it was in the placebo group at 21.579% (95% CI, 16.3571 to 26.8011; n = 100; p < 0.001). The other endpoint, the clinical attachment level regained at 36 weeks, was not significantly different between groups. Study B, a multicenter, randomized, blinded (patients and evaluators of radiographs), and active-controlled study was conducted at 15 centers to clarify the clinical significance of rhFGF-2. Patients with 6-mm and 4-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 274 patients were randomly assigned (5:5:2) to receive rhFGF-2, enamel matrix derivative (EMD), or flap surgery alone. A total of 267 patients received the assigned treatment during flap surgery. The primary endpoint, the linear alveolar bone growth at 36 weeks, was 1.927 mm (95% CI, 1.6615 to 2.1920; n = 108) in the rhFGF-2 group and 1.359 mm (95% CI, 1.0683 to 1.6495; n = 109) in the EMD group, showing non-inferiority (a prespecified margin of 0.3 mm) and superiority of rhFGF-2 to EMD. Safety problems were not identified in either study. Therefore, trafermin is an effective and safe treatment for periodontal regeneration in intrabony defect, and its efficacy was superior in rhFGF-2 compared to EMD treatments.
KW - Cell/Tissue Signaling
KW - Clinical Trials
KW - Cytokines
KW - Dental Biologyx
KW - Endocrine Pathways
UR - http://www.scopus.com/inward/record.url?scp=84952685217&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952685217&partnerID=8YFLogxK
U2 - 10.1002/jbmr.2738
DO - 10.1002/jbmr.2738
M3 - Article
C2 - 26547659
AN - SCOPUS:84952685217
SN - 0884-0431
VL - 31
SP - 806
EP - 814
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 4
ER -
