Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation
Hatice Hasturk, … , Dimitrios C. Mastellos, Despina Yancopoulou
Hatice Hasturk, … , Dimitrios C. Mastellos, Despina Yancopoulou
Published October 7, 2021
Citation Information: J Clin Invest. 2021;131(23):e152973. https://doi.org/10.1172/JCI152973.
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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 1

CONSORT diagram.

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CONSORT diagram. CONSORT subject flow diagram shows the number of subjec...
CONSORT subject flow diagram shows the number of subjects screened, enrolled/randomized, and included in the interim, primary safety, and secondary efficacy analyses. Of the 98 patients screened, 40 were found eligible, agreed to participate, and enrolled in the study. The first 12 subjects were randomized into 3 escalating dose groups (dose group 1, dose group 2, and dose group 3; 4 individuals/group). After selection of the dose of 0.1 mg/interdental papilla, 28 more individuals (total of 32) were randomized to the main study group (orange shaded boxes) and treated split-mouth with AMY-101 at 0.1 mg/interdental papilla and placebo (saline) injections at baseline, on day 7 and on day 14, as 3 once-weekly injections. The safety population included all participants (n = 40) treated with at least 1 dose of AMY-101 or placebo, including the participants from the dose selection phase. The efficacy population included those who completed at least 1 post-baseline visit (starting on day 21) for efficacy analysis in the selected dose group. One participant dropped out before completing the necessary day-21 visit and was thus replaced per protocol. Red asterisk indicate that of the 31 patients treated with AMY-101 at a dose of 0.1 mg/interdental papilla and placebo, 1 failed to complete the day-90 visit; dose group 1: 0.025 mg/interdental papilla; dose group 2: 0.05 mg/interdental papilla; dose group 3: 0.1 mg/interdental papilla.