166. A Phase 2b/3 Study to Evaluate the Efficacy and Safety of an Investigational Respiratory Syncytial Virus (RSV) Antibody, Clesrovimab, in Healthy Preterm and Full-Term Infants
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Background Clesrovimab is an investigational, long-acting monoclonal antibody (mAb) targeting site IV of the fusion protein for the prevention of RSV lower respiratory tract infection in infants. Methods This phase 2b/3 double-blind, randomized, placebo-controlled pivotal study enrolled healthy preterm and full-term infants birth to 1 year of age entering their first RSV season. Participants (pts) were randomized 2:1 to receive clesrovimab (105 mg IM) or placebo on day 1. Safety and tolerability were a primary endpoint. There were two hypothesis-tested endpoints: the efficacy of clesrovimab against RSV-associated medically attended lower respiratory tract infection (MALRI) through day 150 (primary) and against RSV-associated hospitalization through day 150 (secondary). The MALRI definition required ≥1 indicators of lower respiratory tract infection (LRI) or severity. To facilitate comparison across RSV mAb trials, a definition of RSV-associated MALRI that required ≥2 indicators of LRI/severity (≥1 indicator of LRI and ≥1 indicator of severity) was assessed post hoc. Results There were 3,632 pts randomized across 22 countries; >99% received study intervention. RSV-associated efficacy endpoints through day 150 and day 180 are shown in Table 1. Clesrovimab reduced the incidence of RSV-associated MALRI requiring ≥1 indicator of LRI/severity (60.4% [95% CI: 44.1, 71.9], p< 0.001) and ≥2 indicators of LRI/severity (88.0% [95% CI:76.1, 94.0]), RSV hospitalization (84.2% [95% CI: 66.6, 92.6], p< 0.001), and severe MALRI (91.7% [95% CI:62.9, 98.1]) through day 150 postdose compared to placebo. Efficacy increased with increasing RSV-associated disease severity and was similar from days 1-180 compared to days 1-150 across endpoints. The proportions of pts with adverse events (AEs), including injection-site and systemic AEs, drug-related AEs, and serious AEs were comparable between the clesrovimab and placebo groups (Table 2). There were no treatment-related deaths or deaths attributed to RSV disease. Conclusion A single dose of clesrovimab given before or during the first RSV season was efficacious in reducing RSV-associated MALRI and RSV-associated hospitalization in healthy preterm and full-term infants and was generally well tolerated with a safety profile comparable to placebo. Disclosures Heather J. Zar, PhD, MSD, Pfizer, AstraZeneca, Moderna (DSMB): Advisor/Consultant|MSD, Pfizer, AstraZeneca, Moderna (DSMB): Grant/Research Support|MSD, Pfizer, AstraZeneca, Moderna (DSMB): Honoraria|MSD, Pfizer, AstraZeneca, Moderna (DSMB): MSD Principal Investigator for the study and on MSD Advisory Board Eric Simoes, MD DCH, Pfizer, Sanofi, Merck, Icosavax, Enanta Cidara, Adiagio, Nuance, Shionogi, GIlead,: Advisor/Consultant|Pfizer, Sanofi, Merck, Icosavax, Enanta Cidara, Adiagio, Nuance, Shionogi, GIlead,: Grant/Research Support|Pfizer, Sanofi, Merck, Icosavax, Enanta Cidara, Adiagio, Nuance, Shionogi, GIlead,: Honoraria|Pfizer, Sanofi, Merck, Icosavax, Enanta Cidara, Adiagio, Nuance, Shionogi, GIlead,: MSD - PI for this study; DSMB Abbvie, Moderna, GSK Sabhir Madhi, MD, Pfizer, GSK, Medimmune, Merck & Co., Inc., Rahway, NJ, USA: Grant/Research Support|Pfizer, GSK, Medimmune, Merck & Co., Inc., Rahway, NJ, USA: Honoraria Octavio Ramilo, MD, Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Advisor/Consultant|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Grant/Research Support|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Honoraria|Pfizer, Sanofi, Gates Foundation, NIH, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): SAC member for MSD Shelly Senders, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Julie S. Shepard, MD, MPH, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Kamolwish Laoprasopwattana, MD, Merck & Co., Inc., Rahway, NJ, USA: Grant/Research Support|Merck & Co., Inc., Rahway, NJ, USA: MSD - PI for this study Jorge Piedrahita, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Jose M. Novoa Pizarro, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Principal Investigator for the study for MSD Sergio L. Vargas, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Marc Dionne, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Teresa Jackowska, MD, MSD Poland, Merck & Co., Inc, Rahway, NJ, USA: Advisor/Consultant|MSD Poland, Merck & Co., Inc, Rahway, NJ, USA: Grant/Research Support|MSD Poland, Merck & Co., Inc, Rahway, NJ, USA: Honoraria|MSD Poland, Merck & Co., Inc, Rahway, NJ, USA: MSD - PI for this study Enmei Liu, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Yasunori Ishihara, MD, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Kazushige Ikeda, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Principal Investigator Ying Zhang, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Radha A. Railkar, PhD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, US (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, US (MSD): Stocks/Bonds (Public Company) Jeannine Lutkiewicz, BS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Andrew W. Lee, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee at the time of study|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company) Andrea Guerra, MD, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Anushua Sinha, MD, MPH, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD): Stocks/Bonds (Public Company)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it