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Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.


ABSTRACT: Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

SUBMITTER: Skendros P 

PROVIDER: S-EPMC9385148 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.

Skendros Panagiotis P   Germanidis Georgios G   Mastellos Dimitrios C DC   Antoniadou Christina C   Gavriilidis Efstratios E   Kalopitas Georgios G   Samakidou Anna A   Liontos Angelos A   Chrysanthopoulou Akrivi A   Ntinopoulou Maria M   Kogias Dionysios D   Karanika Ioanna I   Smyrlis Andreas A   Cepaityte Dainora D   Fotiadou Iliana I   Zioga Nikoleta N   Mitroulis Ioannis I   Gatselis Nikolaos K NK   Papagoras Charalampos C   Metallidis Simeon S   Milionis Haralampos H   Dalekos George N GN   Willems Loek L   Persson Barbro B   Manivel Vivek Anand VA   Nilsson Bo B   Connolly E Sander ES   Iacobelli Simona S   Papadopoulos Vasileios V   Calado Rodrigo T RT   Huber-Lang Markus M   Risitano Antonio M AM   Yancopoulou Despina D   Ritis Konstantinos K   Lambris John D JD  

Science advances 20220817 33


Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (<i>n</i> = 16) or placebo (<i>n</i> = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101  ...[more]

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