Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study
IntroductionNipocalimab is a high-affinity, fully human, aglycosylated, effectorless, immunoglobulin G (IgG) 1 monoclonal antibody that targets the neonatal Fc receptor (FcRn), decreases systemic IgG including autoantibodies, and is under development in several IgG autoantibody- and alloantibody-med...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1302714/full |
| _version_ | 1797337240953683968 |
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| author | Jocelyn H. Leu An Vermeulen Claudia Abbes Santiago Arroyo William S. Denney Leona E. Ling |
| author_facet | Jocelyn H. Leu An Vermeulen Claudia Abbes Santiago Arroyo William S. Denney Leona E. Ling |
| author_sort | Jocelyn H. Leu |
| collection | DOAJ |
| description | IntroductionNipocalimab is a high-affinity, fully human, aglycosylated, effectorless, immunoglobulin G (IgG) 1 monoclonal antibody that targets the neonatal Fc receptor (FcRn), decreases systemic IgG including autoantibodies, and is under development in several IgG autoantibody- and alloantibody-mediated diseases, including generalized myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, maternal-fetal medicine, and multiple other therapeutic areas. An initial phase 1 study with single and multiple ascending doses of nipocalimab infused intravenously (IV) over 2 h demonstrated dose-dependent serum pharmacokinetics and IgG reductions, with an adverse event (AE) profile comparable to placebo.MethodsThe current investigation evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of nipocalimab across various IV infusion rates in a randomized, double-blind, placebo-controlled, sequential-dose study. Forty participants were randomized to receive nipocalimab 30 mg/kg over 60, 30, 15 or 7.5 min (0.5, 1, 2, or 4 mg/kg/min); nipocalimab 60 mg/kg over 15 min (4 mg/kg/min); or matching placebo.ResultsAt doses up to 60 mg/kg and infusion rates up to 4 mg/kg/min (maximum clinically feasible rate), single doses of nipocalimab were tolerable, with 12 (40%) participants experiencing AEs across nipocalimab cohorts compared with 1 (10%) participant in the placebo cohort. AEs deemed treatment related occurred in 6 (20%) participants receiving nipocalimab and 1 (10%) participant receiving placebo. None of the AEs were severe, and no participants discontinued treatment due to AEs. Nipocalimab provided consistent, dose-dependent serum pharmacokinetics and IgG reductions, regardless of infusion rate.DiscussionThis study supports the use of shortened durations of nipocalimab infusion for future studies. |
| first_indexed | 2024-03-08T09:07:39Z |
| format | Article |
| id | doaj.art-b0db3a96072d4cefb2aece1ceaf0708f |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-08T09:07:39Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-b0db3a96072d4cefb2aece1ceaf0708f2024-02-01T04:25:23ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-02-011810.3389/fnins.2024.13027141302714Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled studyJocelyn H. Leu0An Vermeulen1Claudia Abbes2Santiago Arroyo3William S. Denney4Leona E. Ling5Janssen Research & Development, LLC, Spring House, PA, United StatesJanssen Research & Development, LLC, a Division of Janssen Pharmaceutica NV, Beerse, BelgiumMomenta Pharmaceuticals, Inc., Cambridge, MA, United StatesMomenta Pharmaceuticals, Inc., Cambridge, MA, United StatesHuman Predictions, LLC, Boston, MA, United StatesJanssen Research & Development, LLC, Cambridge, MA, United StatesIntroductionNipocalimab is a high-affinity, fully human, aglycosylated, effectorless, immunoglobulin G (IgG) 1 monoclonal antibody that targets the neonatal Fc receptor (FcRn), decreases systemic IgG including autoantibodies, and is under development in several IgG autoantibody- and alloantibody-mediated diseases, including generalized myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, maternal-fetal medicine, and multiple other therapeutic areas. An initial phase 1 study with single and multiple ascending doses of nipocalimab infused intravenously (IV) over 2 h demonstrated dose-dependent serum pharmacokinetics and IgG reductions, with an adverse event (AE) profile comparable to placebo.MethodsThe current investigation evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of nipocalimab across various IV infusion rates in a randomized, double-blind, placebo-controlled, sequential-dose study. Forty participants were randomized to receive nipocalimab 30 mg/kg over 60, 30, 15 or 7.5 min (0.5, 1, 2, or 4 mg/kg/min); nipocalimab 60 mg/kg over 15 min (4 mg/kg/min); or matching placebo.ResultsAt doses up to 60 mg/kg and infusion rates up to 4 mg/kg/min (maximum clinically feasible rate), single doses of nipocalimab were tolerable, with 12 (40%) participants experiencing AEs across nipocalimab cohorts compared with 1 (10%) participant in the placebo cohort. AEs deemed treatment related occurred in 6 (20%) participants receiving nipocalimab and 1 (10%) participant receiving placebo. None of the AEs were severe, and no participants discontinued treatment due to AEs. Nipocalimab provided consistent, dose-dependent serum pharmacokinetics and IgG reductions, regardless of infusion rate.DiscussionThis study supports the use of shortened durations of nipocalimab infusion for future studies.https://www.frontiersin.org/articles/10.3389/fnins.2024.1302714/fullneonatal Fc receptormonoclonal antibodiesphase 1 clinical trialintravenous infusionspharmacokineticsimmunoglobulin G |
| spellingShingle | Jocelyn H. Leu An Vermeulen Claudia Abbes Santiago Arroyo William S. Denney Leona E. Ling Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study Frontiers in Neuroscience neonatal Fc receptor monoclonal antibodies phase 1 clinical trial intravenous infusions pharmacokinetics immunoglobulin G |
| title | Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study |
| title_full | Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study |
| title_fullStr | Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study |
| title_full_unstemmed | Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study |
| title_short | Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study |
| title_sort | pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab results of a phase 1 placebo controlled study |
| topic | neonatal Fc receptor monoclonal antibodies phase 1 clinical trial intravenous infusions pharmacokinetics immunoglobulin G |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1302714/full |
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