Periodontal Tissue Regeneration Using Fibroblast Growth Factor -2: Randomized Controlled Phase II Clinical Trial

Abstract

BackgroundThe options for medical use of signaling molecules as stimulators of tissue regeneration are currently limited. Preclinical evidence suggests that fibroblast growth factor (FGF)-2 can promote periodontal regeneration. This study aimed to clarify the activity of FGF-2 in stimulating regeneration of periodontal tissue lost by periodontitis and to evaluate the safety of such stimulation.Methodology/Principal FindingsWe used recombinant human FGF-2 with 3% hydroxypropylcellulose (HPC) as vehicle and conducted a randomized double-blinded controlled trial involving 13 facilities. Subjects comprised 74 patients displaying a 2- or 3-walled vertical bone defect as measured ≥3 mm apical to the bone crest. Patients were randomly assigned to 4 groups: Group P, given HPC with no FGF-2; Group L, given HPC containing 0.03% FGF-2; Group M, given HPC containing 0.1% FGF-2; and Group H, given HPC containing 0.3% FGF-2. Each patient underwent flap operation during which we administered 200 µL of the appropriate investigational drug to the bone defect. Before and for 36 weeks following administration, patients underwent periodontal tissue inspections and standardized radiography of the region under investigation. As a result, a significant difference (p = 0.021) in rate of increase in alveolar bone height was identified between Group P (23.92%) and Group H (58.62%) at 36 weeks. The linear increase in alveolar bone height at 36 weeks in Group P and H was 0.95 mm and 1.85 mm, respectively (p = 0.132). No serious adverse events attributable to the investigational drug were identified.ConclusionsAlthough no statistically significant differences were noted for gains in clinical attachment level and alveolar bone gain for FGF-2 groups versus Group P, the significant difference in rate of increase in alveolar bone height (p = 0.021) between Groups P and H at 36 weeks suggests that some efficacy could be expected from FGF-2 in stimulating regeneration of periodontal tissue in patients with periodontitis.Trial RegistrationClinicalTrials.gov NCT00514657

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

“…The estimated size of the rhFGF-2-induced effect from the pooled data in Study A and previous studies (9,10) was about 1.05 mm. A total of 100 patients each in the rhFGF-2 and EMD groups would be needed to determine the non-inferiority with 80% power at a margin of 0.3 mm (about 1/3 of 0.81 mm) under the assumption of about 10% dropout.…”

“…In previously reported exploratory studies, (9,10) rhFGF-2 significantly improved the percentage bone fill compared with the placebo, and the optimal dose of rhFGF-2 for periodontal regeneration was found to be 0.3%. At the phase III trial stage, we conducted Study A to clarify the efficacy and safety of rhFGF-2 in periodontal regeneration.…”

“…The detailed methods for the radiographic measurements have been described previously. (9) The median of five measurements taken from the same image was selected for efficacy analysis.…”

“…Fibroblast growth factor (FGF)-2 exhibits potent angiogenic and mitogenic activity in mesenchymal cells within the periodontal ligament, and has been reported to be effective in regenerating periodontal tissue in animal models. (5)(6)(7)(8) Previously reported exploratory studies (9,10) found that trafermin, a recombinant human FGF-2 (rhFGF-2), significantly improved the percentage bone fill compared, with the placebo, and the optimal dose of rhFGF-2 for periodontal regeneration was 0.3%. Here, we report the results of two recently conducted Phase III studies.…”

Effect of basic fibroblast growth factor on root resorption after delayed autotransplantation of tooth in dogs

“…Clinical safety of FGF-2 has been shown when applied in 23 conjunction with periodontal surgery: the immunogenic potential of FGF-2 was found to be extremely low. 47 The results from the present study suggest that tissue engineering to functionally restore the damaged periodontal tissue could ultimately inhibit replacement resorption. …”