A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in context
Summary: Background: Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a monoclonal antibody may be a more effective and convenient route. We investigated the safety, tolerabilit...
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Elsevier
2025-03-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S235239642500026X |
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| author | Thomas R. Moench Lakshmi Botta Brian Farrer Jason D. Lickliter Hyunah Kang Yoona Park Cheolmin Kim Marshall Hoke Miles Brennan Morgan D. McSweeney Zachary Richardson John B. Whelan Jong Moon Cho Soo Young Lee Frances Faurot Jeff Hutchins Samuel K. Lai |
| author_facet | Thomas R. Moench Lakshmi Botta Brian Farrer Jason D. Lickliter Hyunah Kang Yoona Park Cheolmin Kim Marshall Hoke Miles Brennan Morgan D. McSweeney Zachary Richardson John B. Whelan Jong Moon Cho Soo Young Lee Frances Faurot Jeff Hutchins Samuel K. Lai |
| author_sort | Thomas R. Moench |
| collection | DOAJ |
| description | Summary: Background: Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a monoclonal antibody may be a more effective and convenient route. We investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab for nebulized delivery by a handheld nebulizer. Methods: A Phase 1 study was conducted in healthy volunteers aged 18–55 a Phase 1 unit in Melbourne, Australia (ACTRN12621001235897). Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The ratio of active:placebo randomization to each cohort was set at 3:1. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetics of IN-006 in nasal fluid and serum. Findings: Twenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts (30 mg or 90 mg single nebulized dose, or seven daily 90 mg doses). There were no serious adverse events. All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and graded mild to moderate in severity. Nebulization was well-tolerated and completed in an average of 6 min. Geometric mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 739.8 μg/mL at 30 min after dosing and 1.2 μg/mL at 22 h. Geometric mean serum levels in the multiple dose cohort peaked at 0.51 μg/mL 3 days after the final dose. Interpretation: IN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above the IC50 range typical of antiviral mAbs. These data support further development of nebulized delivery of antiviral mAbs for respiratory infectious disease. Funding: This work was funded by the U.S. Army Medical Research and Development Command (W81XWH-15-9-0001) and regdanvimab was provided by Celltrion, Inc. |
| format | Article |
| id | doaj-art-c52295f8de5d472fa00f4af92237e58c |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-c52295f8de5d472fa00f4af92237e58c2025-02-10T04:34:34ZengElsevierEBioMedicine2352-39642025-03-01113105582A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in contextThomas R. Moench0Lakshmi Botta1Brian Farrer2Jason D. Lickliter3Hyunah Kang4Yoona Park5Cheolmin Kim6Marshall Hoke7Miles Brennan8Morgan D. McSweeney9Zachary Richardson10John B. Whelan11Jong Moon Cho12Soo Young Lee13Frances Faurot14Jeff Hutchins15Samuel K. Lai16Inhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USA; Corresponding author.Inhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USAInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USANucleus Network Pty Ltd, Level 5 Burnet Tower, 89 Commercial Road, Melbourne, VIC, 3004, AustraliaBiotechnology Research Institute, Celltrion Inc, Incheon, 22014, Republic of KoreaBiotechnology Research Institute, Celltrion Inc, Incheon, 22014, Republic of KoreaBiotechnology Research Institute, Celltrion Inc, Incheon, 22014, Republic of KoreaInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USAInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USAInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USAInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USAInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USABiotechnology Research Institute, Celltrion Inc, Incheon, 22014, Republic of KoreaBiotechnology Research Institute, Celltrion Inc, Incheon, 22014, Republic of KoreaInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USAInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USAInhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USA; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 125 Mason Farm Rd, Chapel Hill, NC, 27599, USA; Corresponding author. Inhalon Biopharma, Inc., 5151 McCrimmon Parkway, Suite 220, Research Triangle Park, Morrisville, NC, 27560, USA.Summary: Background: Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a monoclonal antibody may be a more effective and convenient route. We investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab for nebulized delivery by a handheld nebulizer. Methods: A Phase 1 study was conducted in healthy volunteers aged 18–55 a Phase 1 unit in Melbourne, Australia (ACTRN12621001235897). Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The ratio of active:placebo randomization to each cohort was set at 3:1. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetics of IN-006 in nasal fluid and serum. Findings: Twenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts (30 mg or 90 mg single nebulized dose, or seven daily 90 mg doses). There were no serious adverse events. All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and graded mild to moderate in severity. Nebulization was well-tolerated and completed in an average of 6 min. Geometric mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 739.8 μg/mL at 30 min after dosing and 1.2 μg/mL at 22 h. Geometric mean serum levels in the multiple dose cohort peaked at 0.51 μg/mL 3 days after the final dose. Interpretation: IN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above the IC50 range typical of antiviral mAbs. These data support further development of nebulized delivery of antiviral mAbs for respiratory infectious disease. Funding: This work was funded by the U.S. Army Medical Research and Development Command (W81XWH-15-9-0001) and regdanvimab was provided by Celltrion, Inc.http://www.sciencedirect.com/science/article/pii/S235239642500026XSARS-CoV-2Clinical trialPhase IAntibodiesMonoclonalRespiratory system |
| spellingShingle | Thomas R. Moench Lakshmi Botta Brian Farrer Jason D. Lickliter Hyunah Kang Yoona Park Cheolmin Kim Marshall Hoke Miles Brennan Morgan D. McSweeney Zachary Richardson John B. Whelan Jong Moon Cho Soo Young Lee Frances Faurot Jeff Hutchins Samuel K. Lai A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in context EBioMedicine SARS-CoV-2 Clinical trial Phase I Antibodies Monoclonal Respiratory system |
| title | A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in context |
| title_full | A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in context |
| title_fullStr | A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in context |
| title_full_unstemmed | A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in context |
| title_short | A randomized, double-blind, Phase 1, single- and multiple-dose placebo-controlled study of the safety and pharmacokinetics of IN-006, an inhaled antibody treatment for COVID-19 in healthy volunteersResearch in context |
| title_sort | randomized double blind phase 1 single and multiple dose placebo controlled study of the safety and pharmacokinetics of in 006 an inhaled antibody treatment for covid 19 in healthy volunteersresearch in context |
| topic | SARS-CoV-2 Clinical trial Phase I Antibodies Monoclonal Respiratory system |
| url | http://www.sciencedirect.com/science/article/pii/S235239642500026X |
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