A phase I trial of cyclosporine for hospitalized patients with COVID-19
BACKGROUND COVID-19 remains a global health emergency with limited treatment options, lagging vaccine rates, and inadequate healthcare resources in the face of an ongoing calamity. The disease is characterized by immune dysregulation and cytokine storm. Cyclosporine A (CSA) is a calcineurin inhibito...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2022-06-01
|
| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.155682 |
| _version_ | 1818242189367443456 |
|---|---|
| author | Emily A. Blumberg Julia Han Noll Pablo Tebas Joseph A. Fraietta Ian Frank Amy Marshall Anne Chew Elizabeth A. Veloso Alison Carulli Walter Rogal Avery L. Gaymon Aliza H. Schmidt Tiffany Barnette Renee Jurek Rene Martins Briana M. Hudson Kalyan Chavda Christina M. Bailey Sarah E. Church Hooman Noorchashm Wei-Ting Hwang Carl H. June Elizabeth O. Hexner |
| author_facet | Emily A. Blumberg Julia Han Noll Pablo Tebas Joseph A. Fraietta Ian Frank Amy Marshall Anne Chew Elizabeth A. Veloso Alison Carulli Walter Rogal Avery L. Gaymon Aliza H. Schmidt Tiffany Barnette Renee Jurek Rene Martins Briana M. Hudson Kalyan Chavda Christina M. Bailey Sarah E. Church Hooman Noorchashm Wei-Ting Hwang Carl H. June Elizabeth O. Hexner |
| author_sort | Emily A. Blumberg |
| collection | DOAJ |
| description | BACKGROUND COVID-19 remains a global health emergency with limited treatment options, lagging vaccine rates, and inadequate healthcare resources in the face of an ongoing calamity. The disease is characterized by immune dysregulation and cytokine storm. Cyclosporine A (CSA) is a calcineurin inhibitor that modulates cytokine production and may have direct antiviral properties against coronaviruses.METHODS To test whether a short course of CSA was safe in patients with COVID-19, we treated 10 hospitalized, oxygen-requiring, noncritically ill patients with CSA (starting at a dose of 9 mg/kg/d). We evaluated patients for clinical response and adverse events, measured serum cytokines and chemokines associated with COVID-19 hyperinflammation, and conducted gene-expression analyses.RESULTS Five participants experienced adverse events, none of which were serious; transaminitis was most common. No participant required intensive care unit–level care, and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyperinflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I IFN gene expression signatures and other transcriptional profiles associated with exacerbated hyperinflammation in the peripheral blood cells of these patients.CONCLUSION Short courses of CSA appear safe and feasible in patients with COVID-19 who require oxygen and may be a useful adjunct in resource-limited health care settings.TRIAL REGISTRATION This trial was registered on ClinicalTrials.gov (Investigational New Drug Application no. 149997; ClinicalTrials.gov NCT04412785).FUNDING This study was internally funded by the Center for Cellular Immunotherapies. |
| first_indexed | 2024-12-12T13:41:16Z |
| format | Article |
| id | doaj.art-6597f6dab218404fa9ecd0f6232979e4 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T13:41:16Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-6597f6dab218404fa9ecd0f6232979e42022-12-22T00:22:48ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-06-01711A phase I trial of cyclosporine for hospitalized patients with COVID-19Emily A. BlumbergJulia Han NollPablo TebasJoseph A. FraiettaIan FrankAmy MarshallAnne ChewElizabeth A. VelosoAlison CarulliWalter RogalAvery L. GaymonAliza H. SchmidtTiffany BarnetteRenee JurekRene MartinsBriana M. HudsonKalyan ChavdaChristina M. BaileySarah E. ChurchHooman NoorchashmWei-Ting HwangCarl H. JuneElizabeth O. HexnerBACKGROUND COVID-19 remains a global health emergency with limited treatment options, lagging vaccine rates, and inadequate healthcare resources in the face of an ongoing calamity. The disease is characterized by immune dysregulation and cytokine storm. Cyclosporine A (CSA) is a calcineurin inhibitor that modulates cytokine production and may have direct antiviral properties against coronaviruses.METHODS To test whether a short course of CSA was safe in patients with COVID-19, we treated 10 hospitalized, oxygen-requiring, noncritically ill patients with CSA (starting at a dose of 9 mg/kg/d). We evaluated patients for clinical response and adverse events, measured serum cytokines and chemokines associated with COVID-19 hyperinflammation, and conducted gene-expression analyses.RESULTS Five participants experienced adverse events, none of which were serious; transaminitis was most common. No participant required intensive care unit–level care, and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyperinflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I IFN gene expression signatures and other transcriptional profiles associated with exacerbated hyperinflammation in the peripheral blood cells of these patients.CONCLUSION Short courses of CSA appear safe and feasible in patients with COVID-19 who require oxygen and may be a useful adjunct in resource-limited health care settings.TRIAL REGISTRATION This trial was registered on ClinicalTrials.gov (Investigational New Drug Application no. 149997; ClinicalTrials.gov NCT04412785).FUNDING This study was internally funded by the Center for Cellular Immunotherapies.https://doi.org/10.1172/jci.insight.155682COVID-19 |
| spellingShingle | Emily A. Blumberg Julia Han Noll Pablo Tebas Joseph A. Fraietta Ian Frank Amy Marshall Anne Chew Elizabeth A. Veloso Alison Carulli Walter Rogal Avery L. Gaymon Aliza H. Schmidt Tiffany Barnette Renee Jurek Rene Martins Briana M. Hudson Kalyan Chavda Christina M. Bailey Sarah E. Church Hooman Noorchashm Wei-Ting Hwang Carl H. June Elizabeth O. Hexner A phase I trial of cyclosporine for hospitalized patients with COVID-19 JCI Insight COVID-19 |
| title | A phase I trial of cyclosporine for hospitalized patients with COVID-19 |
| title_full | A phase I trial of cyclosporine for hospitalized patients with COVID-19 |
| title_fullStr | A phase I trial of cyclosporine for hospitalized patients with COVID-19 |
| title_full_unstemmed | A phase I trial of cyclosporine for hospitalized patients with COVID-19 |
| title_short | A phase I trial of cyclosporine for hospitalized patients with COVID-19 |
| title_sort | phase i trial of cyclosporine for hospitalized patients with covid 19 |
| topic | COVID-19 |
| url | https://doi.org/10.1172/jci.insight.155682 |
| work_keys_str_mv | AT emilyablumberg aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT juliahannoll aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT pablotebas aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT josephafraietta aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT ianfrank aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT amymarshall aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT annechew aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT elizabethaveloso aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT alisoncarulli aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT walterrogal aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT averylgaymon aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT alizahschmidt aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT tiffanybarnette aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT reneejurek aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT renemartins aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT brianamhudson aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT kalyanchavda aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT christinambailey aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT sarahechurch aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT hoomannoorchashm aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT weitinghwang aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT carlhjune aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT elizabethohexner aphaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT emilyablumberg phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT juliahannoll phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT pablotebas phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT josephafraietta phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT ianfrank phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT amymarshall phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT annechew phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT elizabethaveloso phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT alisoncarulli phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT walterrogal phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT averylgaymon phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT alizahschmidt phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT tiffanybarnette phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT reneejurek phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT renemartins phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT brianamhudson phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT kalyanchavda phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT christinambailey phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT sarahechurch phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT hoomannoorchashm phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT weitinghwang phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT carlhjune phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 AT elizabethohexner phaseitrialofcyclosporineforhospitalizedpatientswithcovid19 |