Nirsevimab, a monoclonal antibody with an extended half-life, is designed to protect infants from respiratory syncytial virus disease after a single intramuscular dose. This placebo-controlled trial ...involving 1447 preterm infants at 164 sites in 23 countries assessed the effectiveness of nirsevimab over 150 days after the dose was administered.
In a randomized, double-blind, placebo-controlled phase 3 trial of the ChAdOx1 nCoV-19 vaccine in over 32,000 participants from the United States, Chile, and Peru, the incidence of serious adverse ...effects was low (including no cases of vaccine-induced immune thrombotic thrombocytopenia) and the vaccine efficacy was 74%. Efficacy was documented in a range of demographic subgroups.
Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. In this clinical trial, a single dose of nirsevimab resulted in a significantly lower incidence of ...medically attended RSV-associated lower respiratory tract infection than that with placebo.
BACKGROUND:MEDI8897 is a recombinant human monoclonal antibody being developed for prophylaxis of serious respiratory syncytial virus (RSV) disease in all infants.
METHODS:In this phase 1b/2a ...dose-escalation study, healthy preterm infants with a gestational age of 32–35 weeks were randomized to receive a single intramuscular injection of MEDI8897 (10, 25 or 50 mg) or placebo. Safety, pharmacokinetics, RSV-neutralizing antibody and antidrug antibody (ADA) assessments were performed during the 360-day follow-up period. Infants who experienced medically attended lower respiratory tract infections (LRTIs) were tested for RSV.
RESULTS:MEDI8897 serum half-life ranged from 62.5–72.9 days. On day 151, 87% of infants in the 50 mg group had serum concentrations above the 90% effective concentration target level of 6.8 µg/mL, and 90% showed a ≥4-fold rise from baseline in serum RSV-neutralizing antibody levels. Adverse events (AEs) were reported in 17 of 18 (94.4%) placebo and 66 of 71 (93.0%) MEDI8897 recipients. Three MEDI8897 recipients experienced 5 serious AEs (3 LRTIs, 2 febrile seizures). ADA was detected at any time postbaseline in 28.2% of MEDI8897 recipients and at day 361 only in 26.5% of subjects. ADA response was not associated with AEs. Five (7%) MEDI8897 recipients experienced medically attended LRTIs through day 150; 1 tested positive for RSV (10 mg group).
CONCLUSIONS:MEDI8897 had a favorable safety profile in healthy preterm infants. The extended half-life of MEDI8897 and demonstrated RSV-neutralizing activity support protection from RSV for the duration of a typical 5-month season after a single 50 mg intramuscular (IM) dose.
BackgroundWe report updated safety, efficacy, and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) from an ongoing phase 3 trial.MethodsAdults at increased risk of SARS-CoV-2 infection were randomized ...(2:1), stratified by age, to receive 2 doses of AZD1222 or placebo. The primary efficacy end point was confirmed SARS-CoV-2 reverse-transcriptase PCR-positive (RT-PCR-positive) symptomatic COVID-19 at 15 or more days after a second dose in baseline SARS-CoV-2-seronegative participants. The 21,634 and 10,816 participants were randomized to AZD1222 and placebo, respectively.FindingsData cutoff for this analysis was July 30, 2021; median follow-up from second dose was 78 and 71 days for the double-blind period (censoring at unblinding or nonstudy COVID-19 vaccination) and 201 and 82 days for the period to nonstudy COVID-19 vaccination (regardless of unblinding) in the AZD1222 and placebo groups, respectively. For the primary efficacy end point in the double-blind period (141 and 184 events; incidence rates: 39.2 and 118.8 per 1,000 person years), vaccine efficacy was 67.0% (P < 0.001). In the period to nonstudy COVID-19 vaccination, incidence of events remained consistently low and stable through 6 months in the AZD1222 group; for the primary efficacy end point (328 and 219 events; incidence rates: 36.4, 108.4) and severe/critical disease (5 and 13 events; incidence rates: 0.6, 6.4), respective vaccine efficacy estimates were 65.1% and 92.1%. AZD1222 elicited humoral immune responses over time, with waning at day 180. No emergent safety issues were seen.ConclusionAZD1222 is safe and well tolerated, demonstrating durable protection and immunogenicity with median follow-up (AZD1222 group) of 6 months.Trial registrationClinicalTrials.gov NCT04516746.FundingAstraZeneca; US government.
MEDI8852 is an IgG1 kappa monoclonal antibody that is being developed to treat patients hospitalized with influenza A. We evaluated the safety and tolerability, pharmacokinetics, and anti-drug ...antibodies (ADA) of a single intravenous dose of MEDI8852 in healthy adult volunteers (NCT02350751). Forty subjects were randomized to receive either MEDI8852 (250, 750, 1,500, or 3000 mg) (n = 32) or placebo (n = 8) on day 1. Dose escalation was based on cumulative safety data through day 8. Subjects were followed through day 101 for safety, pharmacokinetics, and ADA. Treatment-emergent adverse events (TEAEs) were comparable (37.5%; 37.5%); all TEAEs were mild (grade 1) or moderate (grade 2) in severity. The most frequently reported TEAEs were headache (9.4%, 12.5%) and hypoglycemia (12.5%, 12.5%); all subjects with hypoglycemia were asymptomatic and did not require treatment. No subjects discontinued the study due to a TEAE. Mean area under the curve from time 0 to last sampling time point, area under the curve from time 0 to infinity, and observed maximum concentration for MEDI8852 were dose proportional. The terminal half-life ranged from 19.4 to 22.6 days. No ADAs were detected. A population pharmacokinetic model demonstrated good concentration separation between the 750- and 3000-mg dose groups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in ...children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks’ gestational age wGA); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease CHD and/or chronic lung disease of prematurity CLD or born ≤35 wGA). Methods: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. Results: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. Conclusions: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.
Nirsevimab, a monoclonal antibody targeting respiratory syncytial virus, protected against RSV-associated hospitalization and severe lower respiratory tract infection in term and late-preterm infants.
Prevention of respiratory syncytial virus (RSV) illness in infants is a major public health priority, but there is no approved vaccine. Palivizumab is a monoclonal antibody that provides RSV ...prophylaxis but requires 5 monthly injections and is approved only for infants who experience the greatest morbidity and mortality from RSV. Thus, there remains a significant unmet medical need for prevention of RSV disease in healthy infants. MEDI8897 is a recombinant human RSV monoclonal antibody with a modified Fc region that extends its half-life and is being developed as RSV prophylaxis for all infants. In this phase 1, first-in-human, placebo-controlled study, 136 healthy adults were randomized to receive a single dose of MEDI8897 (
= 102) or placebo (
= 34) in 1 of 5 cohorts (300, 1,000, or 3,000 mg intravenously or 100 or 300 mg intramuscularly i.m.) and were monitored for 360 days. The mean half-life of MEDI8897 was 85 to 117 days across dose groups, and bioavailability after 300-mg i.m. dose administration was 77%. Time to maximum concentration following i.m. dosing was 5 to 9 days. Antidrug antibody (ADA) responses were detected in a similar proportion of placebo (15.2%) and MEDI8897 (13.7%) recipients. The safety profile of MEDI8897 was similar to that of the placebo. These results support clinical studies of the i.m. administration of a single dose of MEDI8897 in the target population of infants to provide protection for the duration of the RSV season. (This study has been registered at ClinicalTrials.gov under identifier NCT02114268.).
In a randomized, placebo-controlled, phase 2b clinical trial, an adjuvanted vaccine containing the respiratory syncytial virus (RSV) fusion protein was immunogenic but did not protect older adults ...from disease caused by RSV.
Abstract
Background
Respiratory syncytial virus (RSV) is an important cause of illness in older adults. This study assessed efficacy of a vaccine for prevention of RSV-associated acute respiratory illness (ARI), defined by specified symptoms with virologic confirmation.
Methods
This phase 2b study evaluated RSV postfusion F protein (120 µg) with glucopyranosyl lipid adjuvant (5 µg) in 2% stable emulsion. Subjects aged ≥60 years were randomly assigned at a ratio of 1:1 to receive vaccine or placebo (all received inactivated influenza vaccine). Ill subjects recorded symptoms and provided blood and nasal swab samples.
Results
In the per-protocol population (n = 1894), the incidence of RSV-associated ARI occurring ≥14 days after dosing was 1.7% and 1.6% in the vaccine and placebo groups, respectively, for a vaccine efficacy (VE) of –7.1% (90% confidence interval CI, –106.9%–44.3%). Efficacy was not observed in secondary analyses that included seroresponse to nonvaccine RSV antigens (VE, 8.9%; 90% CI, –28.5%–35.4%) or symptoms combined with seroresponse (VE, 10.0%; 90% CI, –45.4%–44.4%). On day 29, 92.9% of vaccinees had an anti-F immunoglobulin G antibody seroresponse. Overall, 48.5% and 30.9% of RSV vaccine recipients reported local and systemic solicited symptoms, respectively.
Conclusion
The RSV vaccine was immunogenic but did not protect older adults from RSV illness.
Clinical Trials Registration
NCT02508194.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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