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

Masahiro Kitamura, Motoki Akamatsu, Masamitsu Kawanami, Yasushi Furuichi, Takeo Fujii, Mari Mori, Kazushi Kunimatsu, Hidetoshi Shimauchi, Yorimasa Ogata, Matsuo Yamamoto, Taneaki Nakagawa, Shuichi Sato, Koichi Ito, Takefumi Ogasawara, Yuichi Izumi, Kazuhiro Gomi, Kazuhisa Yamazaki, Hiromasa Yoshie, Mitsuo Fukuda, Toshihide Noguchi & 16 others Shogo Takashiba, Hidemi Kurihara, Toshihiko Nagata, Takafumi Hamachi, Katsumasa Maeda, Makoto Yokota, Ryuji Sakagami, Yoshitaka Hara, Kazuyuki Noguchi, Toshi Furuuchi, Takashi Sasano, Enyu Imai, Masatoshi Ohmae, Hayuru Koizumi, Mitsuru Watanuki, Shinya Murakami

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)806-814
Number of pages9
JournalJournal of Bone and Mineral Research
Volume31
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Fingerprint

Fibroblast Growth Factor 2
Dental Enamel
Regeneration
Placebos
Confidence Intervals
Investigational Drugs
Safety
trafermin
Periodontitis
Bone Development
Therapeutics
Bone and Bones
Pharmaceutical Preparations

Keywords

  • Cell/Tissue Signaling
  • Clinical Trials
  • Cytokines
  • Dental Biologyx
  • Endocrine Pathways

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / 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.

In: Journal of Bone and Mineral Research, Vol. 31, No. 4, 01.04.2016, p. 806-814.

Research output: Contribution to journalArticle

Kitamura, M, Akamatsu, M, Kawanami, M, Furuichi, Y, Fujii, T, Mori, M, Kunimatsu, K, Shimauchi, H, Ogata, Y, Yamamoto, M, Nakagawa, T, Sato, S, Ito, K, Ogasawara, T, Izumi, Y, Gomi, K, Yamazaki, K, Yoshie, H, Fukuda, M, Noguchi, T, Takashiba, S, Kurihara, H, Nagata, T, Hamachi, T, Maeda, K, Yokota, M, Sakagami, R, Hara, Y, Noguchi, K, Furuuchi, T, Sasano, T, Imai, E, Ohmae, M, Koizumi, H, Watanuki, M & Murakami, S 2016, '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', Journal of Bone and Mineral Research, vol. 31, no. 4, pp. 806-814. https://doi.org/10.1002/jbmr.2738
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. / 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. In: Journal of Bone and Mineral Research. 2016 ; Vol. 31, No. 4. pp. 806-814.
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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

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.

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KW - Cytokines

KW - Dental Biologyx

KW - Endocrine Pathways

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