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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.

Nirsevimab is a monoclonal antibody targeting respiratory syncytial virus. In this trial, the safety of nirsevimab was assessed in infants eligible to receive palivizumab, including those born preterm (at 35 weeks of gestation or less) and those with congenital heart disease or chronic lung disease of prematurity. No safety concerns were identified.

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.

•An RSV vaccine [F protein±adjuvant] was assessed in subjects aged ≥60 years.•Adjuvant contributed to local reactogenicity, but safety was acceptable.•Adjuvant enhanced both humoral and cellular immune responses.•A robust, antigen dose-dependent, F-specific IFN-γ T cell response was observed.•Dose-dependent increases in humoral responses occurred. Respiratory syncytial virus (RSV) causes significant illness in older adults resulting in substantial health and economic impact. A successful vaccine would reduce morbidity in this growing segment of the population. In this double-blind phase 1 study, subjects 60 years of age and older were enrolled by cohort and randomized to receive vaccines containing escalating doses (20, 50, or 80μg) of soluble RSV fusion protein (sF) alone or adjuvanted with 2.5μg of glucopyranosyl lipid A, a toll-like receptor-4 agonist, in 2% stable emulsion (GLA-SE). Each cohort included 20 vaccine and 4 placebo recipients. Immune responses were evaluated using assays for RSV microneutralizing, anti-F IgG, and palivizumab competitive antibodies and for F-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) responses. The inclusion of adjuvant increased local reactogenicity, with the majority of subjects who received sF and adjuvant reporting low-grade injection site pain or tenderness. At all doses, the safety profile was acceptable for further development. Immune responses were antigen dose-dependent, and the inclusion of adjuvant increased both humoral and cellular immune responses, with responses statistically higher than for placebo recipients in all 4 assays. At the highest dosage level with adjuvant, half of the subjects had a ≥3-fold rise from day 0 in RSV neutralizing antibody titers, and all had a ≥3-fold rise in antibody levels by anti-F IgG and palivizumab competitive antibody assays on day 29. For the day 8 IFNγ ELISPOT assay, 74% of subjects in the highest dosing cohort had a ≥3-fold rise from baseline. The safety and immunogenicity results from this study support inclusion of the GLA-SE adjuvant in this RSV vaccine for older adults and also support assessment of the efficacy of the vaccine in a larger clinical trial. Clinicaltrials.gov NCT02115815.

Abstract Background Influenza is responsible for significant morbidity and mortality and more effective therapeutics are needed. MEDI8852 is a human IgG1 kappa monoclonal antibody that binds to the conserved stalk region of the influenza hemagglutinin protein neutralizing both seasonal and pandemic influenza A strains. MEDI8852 is being developed to treat patients hospitalized with influenza A. The primary objective of this study was to evaluate the safety of MEDI8852 administered either alone or with oseltamivir (OS) in outpatient adults with acute, uncomplicated influenza A. Methods Subjects aged 18 to 65 years with onset of influenza symptoms ≤ 5 days prior to dosing were enrolled. Subjects were randomized into 4 cohorts: Cohort 1: 750 mg MEDI8852 (single intravenous infusion) + 75 mg OS (orally twice a day for 5 days); Cohort 2: 3,000 mg MEDI8852 + 75 mg OS; Cohort 3: placebo + 75 mg OS; or Cohort 4: 3,000 mg MEDI8852. Subjects were followed through Day 10 for solicited symptoms (SS), through Day 28 for adverse events (AEs) and through Day 101 for serious AEs (SAEs) and AEs of special interest (AESIs). Viral shedding was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) through Day 7. Results 126 subjects (31 in Cohort 1; 31 in Cohort 2; 32 in Cohort 3; and 32 in Cohort 4) were enrolled at sites in United States (2015–16) and South Africa (2016). More AEs were reported in the total MEDI8852 group (Cohorts 1, 2 and 4 combined: 39/93, 41.9%) than in placebo group (10/32, 31.3%). Related AEs were similar across the 2 groups (14/93, 15.1% total MEDI8852 group; 5/32, 15.6% placebo group). Most AEs were Grade 1 or Grade 2. The most common AE was bronchitis (11/93, 11.8%; 1/32, 3.1%). One subject in Cohort 2 had a related SAE (and AESI) of Grade 3 infusion-related reaction, which resolved with treatment. There were no deaths or discontinuations due to an AE. Median (range) time to resolution of SS were similar across groups (93/94, 111.3 [92.4, 130.8] hours; 32/32, 108.8 [71.2, 161.8] hours). Median (range) decreases in viral shedding (log10 viral copies/mL) were similar across groups (-3.6 [-6.2. 0.5]; -3.4 [-5.9, 0.9]). Conclusion MEDI8852 has an acceptable safety profile in adults with acute, uncomplicated influenza A. These results support the continued development of MEDI8852 for the treatment of influenza A. Disclosures O. Ali, MedImmune: Employee, Salary; T. Takas, MedImmune: Employee and Shareholder, Salary and stock; A. C. Nyborg, MedImmune: Employee, Salary; K. M. Jensen, MedImmune: Employee and Shareholder, Salary and stock; F. Dubovsky, MedImmune: Employee and Shareholder, Salary and stock; R. Mallory, MedImmune: Employee, Salary

Abstract Background RSV is the most common cause of lower respiratory tract infection (LRTI) among infants making prevention of RSV disease a public health priority. A significant unmet need exists for RSV prevention in healthy infants. Our goal is to develop a mAb with an extended half-life (t½) capable of protecting infants for an entire RSV season by using a single intramuscular (IM) dose. This study was conducted to evaluate the safety profile, pharmacokinetics (PK), RSV neutralizing antibody titers, and anti-drug antibody (ADA) responses for MEDI8897 in healthy preterm infants born between 32 and 35 weeks gestational age. Methods Infants were randomized 4:1 to receive a single IM injection of MEDI8897 10mg (n = 8), 25mg (n = 31), 50mg (n = 32) or placebo (n = 18) and followed for 360 days. Enrollment occurred during the 2,015 RSV seasons in the US, South Africa, and Chile. Blood was collected at multiple timepoints. Infants who met criteria for a medically-attended (MA) LRTI had nasal swabs obtained for RSV testing by RT-PCR. Results A total of 85/89 (95.5%) infants completed the study. Adverse events (AEs) were reported in 17/18 (94.4%) placebo and 66/71 (93.0%) MEDI8897 recipients. Five serious AEs (three LRTIs, two febrile seizures) were reported in three MEDI8897 recipients. No events were consistent with hypersensitivity reactions. The estimated MEDI8897 serum t½ ranged from 62.5 to 72.9 days. On day 151, 87% of the infants who received the 50mg dose of MEDI8897 had serum concentrations above the target EC90 level of 6.8 µg/ml, and 93.3% showed a ≥3-fold rise from baseline in serum anti-RSV neutralizing antibody titers. ADA was detected in 28.2% of MEDI8897 recipients, but when present was not associated with any safety findings. ADA was detected at day 361 only in 26.5% of subjects. MA-LRTI was reported in 5 (7%) MEDI8897 recipients through 150 days after dosing. The one subject with an MA-LRTI caused by RSV had received a 10mg dose of MEDI8897. Conclusion In healthy preterm infants, the safety profile of MEDI8897 was favorable. The extended t½ of MEDI8897 with the corresponding increase in RSV neutralizing antibody levels was confirmed and supports protection from RSV disease during a typical 5-month season with a single 50mg IM dose. This study was sponsored by MedImmune. Disclosures J. B. Domachowske, Medimmune: Investigator, Research grant; Regeneron: Investigator, Research grant; Pfizer: Investigator, Research grant; Glaxo Smith Kline: Investigator, Research grant; Novavax: Investigator, Research grant; Janssen: Investigator, Research grant; A. Khan, MedImmune: Employee and Shareholder, Salary and stock; M. T. Esser, MedImmune: Employee and Shareholder, Salary and stock; K. M. Jensen, MedImmune: Employee and Shareholder, Salary and stock; T. Takas, MedImmune: Employee and Shareholder, Salary and stock; T. Villafana, MedImmune: Employee and Shareholder, Salary and stock; F. Dubovsky, MedImmune: Employee and Shareholder, Salary and stock; M. P. Griffin, MedImmune: Employee and Shareholder, Salary and stock