BACKGROUND. Gingivitis and periodontitis are prevalent inflammatory diseases of the periodontal tissues. Current treatments are often ineffective or do not prevent disease recurrence. Uncontrolled complement activation and resulting chronic gingival inflammation is a hallmark of periodontal diseases. We determined efficacy and safety of a complement 3-targeted therapeutic, AMY-101, locally administered in adults with periodontal inflammation.
METHODS. Thirty-two patients with gingival inflammation were enrolled into a randomized, placebo-controlled, double-blind, split-mouth design phase 2a trial, after dose-escalation study to select safe and effective dose with additional 8 patients. Half of the mouth was randomly assigned to AMY-101 (0.1mg/site) or placebo injections at sites of inflammation, administered on days 0, 7 and 14 and evaluated for safety and efficacy outcomes at days 28, 60 and 90. The primary efficacy outcome was change in gingival inflammation, measured by modified gingival index (MGI), and secondary outcomes included changes in bleeding-on-probing (BOP), amount of plaque, pocket depth, clinical attachment level, and gingival crevicular fluid levels of matrix metalloproteinases (MMPs) over 90 days.
RESULTS. A once-per-week intragingival injection of AMY-101 for 3 weeks was safe and well-tolerated in all participants resulting in significant (P<0.001) reductions in clinical indices measuring gingival inflammation (MGI and BOP). AMY-101 significantly (P<0.05) reduced MMP-8 and MMP-9 levels, indicators of inflammatory tissue destruction. These therapeutic effects persisted for at least 3 months post-treatment.
CONCLUSION. AMY-101 causes significant and sustainable reduction in gingival inflammation without adverse events and merits further investigation for the treatment of periodontitis and other oral or peri-implant inflammatory conditions.
TRIAL REGISTRATION. ClinicalTrials.gov: NCT03694444.
FUNDING. Amyndas Pharmaceuticals. Amyndas contributed to the design and conducts of the clinical trial and in the writing of the manuscript.
Hasturk H, Hajishengallis G, Lambris JD, Mastellos DM, Yancopoulou D. (2021). Phase 2a clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. J Clin Invest. [Online ahead of print].