Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation
Hatice Hasturk, George Hajishengallis, The Forsyth Institute Center for Clinical and Translational Research staff, John D. Lambris, Dimitrios C. Mastellos, Despina Yancopoulou
Hatice Hasturk, George Hajishengallis, The Forsyth Institute Center for Clinical and Translational Research staff, John D. Lambris, Dimitrios C. Mastellos, Despina Yancopoulou
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Clinical Research and Public Health Immunology

Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation

Abstract

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 the resulting chronic gingival inflammation are hallmarks of periodontal diseases. We determined the efficacy and safety of a complement 3–targeted therapeutic, AMY-101, which was locally administered to adult patients with periodontal inflammation.Methods Thirty-two patients with gingival inflammation were enrolled in a randomized, placebo-controlled, double-blind, split-mouth phase IIa trial that followed a dose escalation study to select a safe and effective dose in an additional 8 patients. Half of the patient’s mouth was randomly assigned to AMY-101 (0.1 mg/site) or placebo injections at sites of inflammation, administered on days 0, 7, and 14, and then evaluated for safety and efficacy outcomes on days 28, 60, and 90. The primary efficacy outcome was a change in gingival inflammation, measured by a modified gingival index (MGI), and secondary outcomes included changes in bleeding on probing (BOP), the amount of plaque, pocket depth, clinical attachment level, and gingival crevicular fluid levels of matrix metalloproteinases (MMPs) over 90 days.Results A once-weekly intragingival injection of AMY-101 for 3 weeks was safe and well tolerated in all participants and resulted 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 after treatment.Conclusion AMY-101 treatment resulted in a significant and sustainable reduction in gingival inflammation without adverse events and, we believe, merits further investigation for the treatment of periodontitis and other oral or peri-implant inflammatory conditions.Trial registration ClinicalTrials.gov identifier NCT03694444.Funding Amyndas Pharmaceuticals.

Authors

Hatice Hasturk, George Hajishengallis, The Forsyth Institute Center for Clinical and Translational Research staff, John D. Lambris, Dimitrios C. Mastellos, Despina Yancopoulou

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Figure 5

Changes in the GCF levels of MMP-8 and MMP-9 following treatment with AMY-101.

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Changes in the GCF levels of MMP-8 and MMP-9 following treatment with AM...
The levels of MMP-8 (A) and MMP-9 (B) were measured in the GCF from 2 separate sites on each treatment side (AMY-101 or saline) and were compared within groups (e.g., different time points after AMY-101 treatment) as well as between groups (i.e., AMY-101 vs. saline). The LSM, its 95 % CI, SE, and LSM difference, along with its SE, 95% CI, and the P value, were obtained through a GEE method with normal distribution and identity link including treatment group, study visit (day 21, day 28, day 60, and day 90), and interaction between the treatment group and study visit as fixed effects with the baseline as the covariate. Dot plots with whiskers represent individual values and the mean ± SE. Within-group comparisons were performed using repeated-measures 1-way ANOVA followed by Sidak’s multiple-comparison test. *P < 0.05, **P < 0.01, and ***P < 0.001. For baseline (day 0), day 21, and day 28, n = 62; for day 60, n = 56; and for day 90, n = 60.