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

• Published in: Journal of bone and mineral research Vol. 31; no. 4; pp. 806 - 814
• Main Authors: Kitamura, Masahiro, Akamatsu, Motoki, Kawanami, Masamitsu, Furuichi, Yasushi, Fujii, Takeo, Mori, Mari, Kunimatsu, Kazushi, Shimauchi, Hidetoshi, Ogata, Yorimasa, Yamamoto, Matsuo, Nakagawa, Taneaki, Sato, Shuichi, Ito, Koichi, Ogasawara, Takefumi, Izumi, Yuichi, Gomi, Kazuhiro, Yamazaki, Kazuhisa, Yoshie, Hiromasa, Fukuda, Mitsuo, Noguchi, Toshihide, Takashiba, Shogo, Kurihara, Hidemi, Nagata, Toshihiko, Hamachi, Takafumi, Maeda, Katsumasa, Yokota, Makoto, Sakagami, Ryuji, Hara, Yoshitaka, Noguchi, Kazuyuki, Furuuchi, Toshi, Sasano, Takashi, Imai, Enyu, Ohmae, Masatoshi, Koizumi, Hayuru, Watanuki, Mitsuru, Murakami, Shinya
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2016
• Subjects: Adult; Aged; CELL/TISSUE SIGNALING; CLINICAL TRIALS; CYTOKINES; DENTAL BIOLOGY; Dental Enamel - physiology; Double-Blind Method; ENDOCRINE PATHWAYS; Extracellular Matrix - metabolism; Female; Fibroblast Growth Factor 2 - administration & dosage; Fibroblast Growth Factors - administration & dosage; Humans; Male; Middle Aged; Peptide Fragments - administration & dosage; Periodontitis - drug therapy; Periodontitis - metabolism; Recombinant Proteins - administration & dosage; Regeneration - drug effects; CELL/TISSUE SIGNALING; ENDOCRINE PATHWAYS; CYTOKINES; DENTAL BIOLOGY; CLINICAL TRIALS
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.2738

ABSTRACT 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. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).