Open Access

Journal of Infectious Diseases

A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants

Shabir A. Madhi ¹

ERIC A. F. SIMOES ^{2, 3, 4}

Armando Acevedo ⁵

Jose M Novoa Pizarro ⁶

Julie S. Shepard ^{7, 8}

Radha A. Railkar ^{9, 10}

Xin Cao ^{9, 10}

Brian M Maas ^{9, 10}

Xiaowei Zang ^{9, 10}

Andrea Krick ^{9, 10}

Brad Roadcap ^{9, 10}

Kalpit A. Vora ^{9, 10}

Antonios O. Aliprantis ^{9, 10}

Andrew W. Lee ^{9, 10}

ANUSHUA SINHA ^{9, 10}

Hide authors affiliations Show authors affiliations: 10 affiliations

South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg, Gauteng ,

University of the Witwatersrand

South African Medical Research Council

Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA; and Colorado School of Public Health , Aurora, Colorado ,

University of Colorado Anschutz Medical Campus

Children's Hospital Colorado

Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, Colorado ,

University of Colorado Anschutz Medical Campus

Children's Hospital Colorado

⁴

Colorado School of Public Health , Aurora, Colorado , |

⁵

Acevedo Clinical Research Associates , Miami, Florida , |

⁶

Hospital Padre Alberto Hurtado , Santiago , |

⁷

Ohio Pediatric Research Association , Dayton, OH ,

⁸

Ohio Pediatric Research Association , Dayton, Ohio , |

⁹

Merck & Co., Inc. , Rahway, NJ , |

¹⁰

Merck & Co, Inc , Rahway, New Jersey ,

Publication type: Journal Article

Publication date: 2024-11-27

Oxford University Press

Journal of Infectious Diseases

scimago Q1

wos Q1

SJR: 2.038

CiteScore: 11.1

Impact factor: 4.5

ISSN: 00221899, 15376613

DOI: 10.1093/infdis/jiae581

Copy DOI

PubMed ID: 39601265

Abstract

Background

Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants.

Methods

In this phase 1b/2a, double-blind study,183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm: 20, 50, 75 or 100-mg, full-term: 100 mg) to receive one dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and anti-drug antibodies (ADA). The incidence of RSV-associated endpoints [medically-attended lower respiratory tract infection (MALRI), hospitalization, and acute respiratory infection (ARI)] were also evaluated through 150 days postdose.

Results

The most common adverse event (AE) through day 14 was irritability; no treatment-related serious AEs were reported. Clesrovimab serum concentrations displayed a geometric mean apparent half-life of 44.9 days. Of participants receiving clesrovimab, 51 (36.7%) developed ADA with no apparent impact in pharmacokinetics. SNA titers increased in a dose-dependent manner at day 150. The incidences of RSV-associated endpoints were lower in infants treated with clesrovimab compared with placebo.

Conclusion

Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies supporting its ongoing development in late-stage trials.

Clinical Trial Registration

Clinicaltrials.gov, NCT03524118

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GOST |

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GOST Copy

Madhi S. A. et al. A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants // Journal of Infectious Diseases. 2024.

GOST all authors (up to 50) Copy

Madhi S. A., SIMOES E. A. F., Acevedo A., Novoa Pizarro J. M., Shepard J. S., Railkar R. A., Cao X., Maas B. M., Zang X., Krick A., Roadcap B., Vora K. A., Aliprantis A. O., Lee A. W., SINHA A. A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants // Journal of Infectious Diseases. 2024.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1093/infdis/jiae581

UR - https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae581/7909258

TI - A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants

T2 - Journal of Infectious Diseases

AU - Madhi, Shabir A.

AU - SIMOES, ERIC A. F.

AU - Acevedo, Armando

AU - Novoa Pizarro, Jose M

AU - Shepard, Julie S.

AU - Railkar, Radha A.

AU - Cao, Xin

AU - Maas, Brian M

AU - Zang, Xiaowei

AU - Krick, Andrea

AU - Roadcap, Brad

AU - Vora, Kalpit A.

AU - Aliprantis, Antonios O.

AU - Lee, Andrew W.

AU - SINHA, ANUSHUA

PY - 2024

DA - 2024/11/27

PB - Oxford University Press

PMID - 39601265

SN - 0022-1899

SN - 1537-6613

ER -

BibTex

Cite this

BibTex (up to 50 authors) Copy

@article{2024_Madhi,

author = {Shabir A. Madhi and ERIC A. F. SIMOES and Armando Acevedo and Jose M Novoa Pizarro and Julie S. Shepard and Radha A. Railkar and Xin Cao and Brian M Maas and Xiaowei Zang and Andrea Krick and Brad Roadcap and Kalpit A. Vora and Antonios O. Aliprantis and Andrew W. Lee and ANUSHUA SINHA},

title = {A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants},

journal = {Journal of Infectious Diseases},

year = {2024},

publisher = {Oxford University Press},

month = {nov},

url = {https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae581/7909258},

doi = {10.1093/infdis/jiae581}

}

Publisher

Oxford University Press

Journal

Journal of Infectious Diseases

scimago Q1

wos Q1

SJR

2.038

CiteScore

11.1

Impact factor

4.5

ISSN

00221899 (Print)

15376613 (Electronic)