scholarly journals 16. A Randomized Phase 1 Study of a Novel Pneumococcal Conjugate Vaccine in Healthy Japanese Adults in the United States

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S30-S31
Author(s):  
David Fitz-Patrick ◽  
Mariano Young Jr. ◽  
Daniel Scott ◽  
Ingrid L Scully ◽  
Gary Baugher ◽  
...  
Keyword(s):  
United States ◽  
Conjugate Vaccine ◽  
Phase 1 ◽  
Geometric Mean ◽  
Age Groups ◽  
Unmet Need ◽  
The United States ◽  
Double Blind Study ◽  
Double Blind ◽  
Japanese Adults

Abstract Background Because of the number and variability of serotypes causing pneumococcal disease among different geographic regions, age groups, and environmental backgrounds, expanding serotype coverage with pneumococcal conjugate vaccines (PCVs) is a continued unmet need. Methods This phase 1, randomized, double-blind study included healthy Japanese adults aged 18–49 years residing in the United States. Subjects were randomized 1:1:1 to receive a single dose of a 20-valent PCV (containing 13-valent PCV [PCV13] serotypes plus 8, 10A, 11A, 12F, 15B, 22F, 33F), a novel pneumococcal polysaccharide conjugate vaccine with extended coverage, or PCV13 (control). Safety was the primary endpoint and included reactogenicity events occurring ≤ 14 days after vaccination, adverse events (AEs) ≤ 1 month after vaccination, and serious AEs (SAEs) ≤ 6 months after vaccination. The secondary endpoint was pneumococcal serotype-specific immunogenicity as determined by opsonophagocytic activity (OPA) titers on sera collected before and 1 month after vaccination. Results Overall, 35 subjects received PCV20 and 35 subjects received PCV13. One subject withdrew before the 1-month follow-up. Local reactions and systemic events across groups were generally mild or moderate (Figure 1). Two vaccine-related AEs occurred (injection site erythema and swelling in the PCV20 group); no severe AEs, SAEs, or safety-related withdrawals were reported. OPA geometric mean titers increased for all 20 serotypes in the PCV20 group and all 13 serotypes in the PCV13 group 1 month after vaccination; corresponding OPA geometric mean fold rises from baseline to 1 month after vaccination are reported (Figure 2; Figure 3). Figure 1 Figure 2 Figure 3 Conclusion PCV20 was well tolerated and induced serotype-specific functional OPA immune responses that are anticipated to be associated with protection in Japanese adults. ClinicalTrials.gov: NCT03642847. Funding: Pfizer Inc. Disclosures David Fitz-Patrick, MD, Pfizer Inc (Grant/Research Support) Mariano Young Jr., MD, Pfizer Inc (Employee, Shareholder) Daniel Scott, MD, Pfizer (Employee, Shareholder) Ingrid L. Scully, PhD, Pfizer Inc (Employee, Shareholder) Gary Baugher, PharmD, Pfizer Inc (Employee, Shareholder) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Wendy Watson, MD, Pfizer (Employee, Shareholder)

scholarly journals 2725. Immunogenicity and Safety of a Booster Dose of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Adolescents and Adults

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S959-S959
Author(s):  
James Hedrick ◽  
Michael W Simon ◽  
Shane Christensen ◽  
German Anez ◽  
Judy Pan ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Booster Dose ◽  
Geometric Mean ◽  
Safety Data ◽  
The United States ◽  
Phase Iii ◽  
Double Blind Study ◽  
Double Blind ◽  
Post Vaccination ◽  
Quadrivalent Meningococcal Conjugate Vaccine

Abstract Background The MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine that contains tetanus toxoid as carrier protein. Vaccine is intended for global use in all age groups (i.e., individuals 6 weeks of age and older). This Phase III study evaluated the safety and immunogenicity of the vaccine when compared with a licensed quadrivalent meningococcal conjugate vaccine in individuals ≥ 15 years of age. Methods A randomized, modified double-blind study (NCT02752906) was conducted in the United States and Puerto Rico. The study evaluated 810 participants primed with a licensed quadrivalent meningococcal conjugate vaccine (Menactra® [MenACWY-D] or MENVEO® [MenACWY-CRM]) in the 4 to 10 years prior to enrollment. Participants were randomly assigned to receive either a single booster dose of MenACYW-TT conjugate vaccine or MenACWY-D. Safety data were collected up to 6 months post-vaccination. Results Non-inferiority of immune response was demonstrated for MenACYW-TT vs. MenACWY-D based on percentages of participants achieving an serum bactericidal assay with human complement (hSBA) seroresponse for serogroups A, C, W, and Y at Day 30 post-vaccination. Post-vaccination hSBA geometric mean titers (GMTs) were higher following administration of MenACYW-TT compared with MenACWY-D for age subgroups ≥15 to < 18 years and ≥18 years. Relative to MenACWY-D, post-vaccination hSBA GMTs were higher for all 4 serogroups following administration of MenACYW-TT in participants who received the priming vaccine < 7 years prior to the booster; for participants who received priming vaccine ≥7 years prior to booster, post-vaccination GMTs were higher for serogroups C, W and Y, and comparable for serogroup A. In MenACWY-CRM-primed subjects, hSBA vaccine seroresponse rates were comparable for all 4 serogroups regardless of the booster vaccine administered. In MenACWY-D-primed subjects, hSBA seroresponse rates following MenACYW-TT booster administration were comparable for serogroups A and Y, and higher for serogroups C and W. Reactogenicity profiles were comparable across study groups. Conclusion MenACYW-TT conjugate vaccine was immunogenic and well tolerated when administered as a booster dose to individuals ≥15 years of age. Disclosures All authors: No reported disclosures.

scholarly journals Impact of Pneumococcal Conjugate Vaccination of Infants on Pneumonia and Influenza Hospitalization and Mortality in All Age Groups in the United States

mBio ◽  
2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Lone Simonsen ◽  
Robert J. Taylor ◽  
Yinong Young-Xu ◽  
Michael Haber ◽  
Larissa May ◽  
...  
Keyword(s):  
United States ◽  
Cause Of Death ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Pneumococcal Disease ◽  
Pneumococcal Pneumonia ◽  
Herd Immunity ◽  
Age Groups ◽  
The United States ◽  
Conjugate Vaccination

ABSTRACT A seven-valent pneumococcal conjugate vaccine (PCV7) introduced in the United States in 2000 has been shown to reduce invasive pneumococcal disease (IPD) in both vaccinated children and adults through induction of herd immunity. We assessed the impact of infant immunization on pneumococcal pneumonia hospitalizations and mortality in all age groups using Health Care Utilization Project State Inpatient Databases (SID) for 1996 to 2006 from 10 states; SID contain 100% samples of ICD9-coded hospitalization data for the selected states. Compared to a 1996–1997 through 1998–1999 baseline, by the 2005–2006 season, both IPD and pneumococcal pneumonia hospitalizations and deaths had decreased substantially in all age groups, including a 47% (95% confidence interval [CI], 38 to 54%) reduction in nonbacteremic pneumococcal pneumonia (ICD9 code 481 with no codes indicating IPD) in infants <2 years old and a 54% reduction (CI, 53 to 56%) in adults ≥65 years of age. A model developed to calculate the total burden of pneumococcal pneumonia prevented by infant PCV7 vaccination in the United States from 2000 to 2006 estimated a reduction of 788,838 (CI, 695,406 to 875,476) hospitalizations for pneumococcal pneumonia. Ninety percent of the reduction in model-attributed pneumococcal pneumonia hospitalizations occurred through herd immunity among adults 18 years old and older; similar proportions were found in pneumococcal disease mortality prevented by the vaccine. In the first seasons after PCV introduction, when there were substantial state differences in coverage among <5-year-olds, states with greater coverage had significantly fewer influenza-associated pneumonia hospitalizations among children, suggesting that PCV7 use also reduces influenza-attributable pneumonia hospitalizations. IMPORTANCE Pneumonia is the world’s leading cause of death in children and the leading infectious cause of death among U.S. adults 65 years old and older. Pneumococcal conjugate vaccination of infants has previously been shown to reduce invasive pneumococcal disease (IPD) among seniors through prevention of pneumococcal transmission from infants to adults (herd immunity). Our analysis documents a significant vaccine-associated reduction not only in IPD but also in pneumococcal pneumonia hospitalizations and inpatient mortality rates among both vaccinated children and unvaccinated adults. We estimate that fully 90% of the reduction in the pneumonia hospitalization burden occurred among adults. Moreover, states that more rapidly introduced their infant pneumococcal immunization programs had greater reductions in influenza-associated pneumonia hospitalization of children, presumably because the vaccine acts to prevent the pneumococcal pneumonia that frequently follows influenza virus infection. Our results indicate that seven-valent pneumococcal conjugate vaccine use has yielded far greater benefits through herd immunity than have previously been recognized.

Oral Rehydration Therapy for Acute Diarrhea in Ambulatory Children in the United States: A Double-Blind Comparison of Four Different Solutions

PEDIATRICS ◽  
1985 ◽  
Vol 76 (2) ◽  
pp. 159-166 ◽  
Author(s):  
Mathuram Santosham ◽  
Barbara Burns ◽  
Vinay Nadkarni ◽  
Stephan Foster ◽  
Steven Garrett ◽  
...  
Keyword(s):  
United States ◽  
Acute Diarrhea ◽  
Oral Rehydration Therapy ◽  
The United States ◽  
Double Blind Study ◽  
Double Blind ◽  
Oral Rehydration ◽  
Rehydration Solutions ◽  
Few Data ◽  
Us Children

Oral rehydration solutions containing 50 to 90 mmol/L of sodium have recently been recommended for the treatment of diarrhea in both hospitalized and ambulatory children in the United States. Few data are available, however, from ambulatory US children. Therefore, we conducted a randomized double-blind study comparing the use of four different oral rehydration solutions with differing concentrations of sodium, glucose, and base. Ambulatory children less than 2 years of age with acute diarrhea (N = 140) were randomly chosen to receive solutions containing sodium at 90 (solution A), 50 (solution B), and 30 mmol/L (solutions C and D). All oral rehydration solutions contained 20 g/L of glucose except solution D which contained 50 g/L of glucose. Solution A contained bicarbonate as its base source whereas the other three contained citrate. All but three (98%) children were treated uneventfully according to the study protocol, and there were no differences among groups in measurements of clinical outcome. It was concluded that in ambulatory US children, oral rehydration solutions containing 90, 50, or 30 mmol/L of sodium can be used safely for the treatment of mild acute diarrhea and that citrate is as efficacious as bicarbonate in the correction of acidosis.

scholarly journals 1240. Persistence of Circulating Antibody Through 12 Months Following Vaccination With a 20-Valent Pneumococcal Conjugate Vaccine in Adults 60–64 Years of Age

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S639-S639
Author(s):  
Donald Hurley ◽  
Carl Griffin ◽  
Mariano Young Jr. ◽  
Daniel Scott ◽  
Michael W Pride ◽  
...  
Keyword(s):  
Immune Responses ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Unmet Need ◽  
Control Group ◽  
Double Blind Study ◽  
Double Blind ◽  
Antibody Persistence ◽  
Phase 2 Study ◽  
Polysaccharide Composition

Abstract Background While widespread use of pneumococcal conjugate vaccines (PCVs) has reduced disease burden, expanding serotype coverage remains an unmet need in disease prevention. The 20-valent PCV (PCV20) contains capsular polysaccharide conjugates from serotypes included in the 13-valent PCV (PCV13; Prevnar 13®) as well as 7 additional serotypes. In a phase 2 study of PCV20 in adults 60–64 years of age, robust immune responses were observed at 1 month after vaccination; antibody persistence up to 12 months after vaccination from that study is described herein. Methods In this randomized, active-controlled, double-blind study (ClinicalTrials.gov NCT03313037), adults aged 60–64 years received a single PCV20 dose followed 1 month later by saline placebo or PCV13 followed 1 month later by 23-valent pneumococcal polysaccharide vaccine (PPSV23), which provided benchmarks for all PCV20 serotypes. Immunogenicity was assessed at baseline and at 1 and 12 months after vaccination as serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs). OPA and IgG geometric mean fold rises (GMFRs) from baseline to 12 months after vaccination were assessed. Results In the PCV20 group, OPA GMTs (n=185–200 at Month 12) for all PCV20 serotypes increased substantially from baseline to 1 month after vaccination and then declined by Month 12 but remained elevated above baseline. OPA GMFRs from baseline to Month 12 after PCV20 vaccination were 1.9–15.0 for the serotypes in common with PCV13 and 5.6–15.6 for the 7 additional serotypes. Similar results were observed for IgG concentrations, with GMFRs of 2.4–9.4 for the PCV13 serotypes and 3.0–15.5 for the 7 additional serotypes. At Month 12, 11 months after PPSV23 vaccination (n=162–195), OPA GMFRs were 5.3–11.5 for the 7 additional serotypes; IgG GMFRs were 5.0–10.4. Benchmarking to PCV13 serotypes in the control group was not appropriate as these subjects received both PCV13 and PPSV23, which overlap in polysaccharide composition for 12 serotypes. Conclusion Immune responses induced by PCV20 persisted at 12 months after vaccination in adults 60–64 years of age, further supporting the potential of PCV20 to expand serotype protection against adult pneumococcal disease. Disclosures Mariano Young Jr., MD, Pfizer Inc (Employee, Shareholder) Daniel Scott, MD, Pfizer (Employee, Shareholder) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Ingrid L. Scully, PhD, Pfizer Inc (Employee, Shareholder) John Ginis, BS, Pfizer Inc (Employee, Shareholder) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Wendy Watson, MD, Pfizer (Employee, Shareholder)

scholarly journals A randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Miwa Haranaka ◽  
James Baber ◽  
Yoichiro Ogama ◽  
Masako Yamaji ◽  
Masakazu Aizawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Geometric Mean ◽  
Randomized Study ◽  
Age Groups ◽  
Serious Adverse Events ◽  
Robust Immune Response ◽  
Japanese Adults ◽  
To Receive ◽  
Ongoing Phase

AbstractWe report interim safety and immunogenicity findings from an ongoing phase 1/2 study of BNT162b2 in healthy Japanese adults. Participants were randomized 3:1 to receive 2 intramuscular injections of 30 μg BNT162b2 or placebo 21 days apart. Overall, 160 individuals were randomized: 119 received BNT162b2, and 41 received placebo. Participants were stratified by age: 20–64 years (n = 130) and 65–85 years (n = 30). More than 97% of BNT162b2 recipients received 2 doses. Local reactions and systemic events were generally transient and mild to moderate. Severe adverse events were uncommon; there were no serious adverse events. One month after dose 2, SARS-CoV-2 50% serum neutralizing geometric mean titers were 571 and 366, and geometric mean fold rises were 55.8 and 36.6, in the younger and older age groups, respectively. In summary, BNT162b2 has an acceptable safety profile and produces a robust immune response, regardless of age, in Japanese adults. (ClinicalTrials.gov, NCT04588480).

scholarly journals Incidence of Benign Meningiomas in the United States: Current and Future Trends

2021 ◽  
Author(s):  
Sonia Bhala ◽  
Douglas R Stewart ◽  
Victoria Kennerley ◽  
Valentina I Petkov ◽  
Philip S Rosenberg ◽  
...  
Keyword(s):  
United States ◽  
Age Groups ◽  
Cancer Registries ◽  
Health Impact ◽  
The United States ◽  
Birth Cohorts ◽  
Benign Meningioma ◽  
Case Count ◽  
Future Burden ◽  
Rate Ratios

Abstract Background Benign meningiomas are the most frequently reported central nervous system tumors in the United States (US), with increasing incidence in past decades. However, the future trajectory of this neoplasm remains unclear. Methods We analyzed benign meningioma incidence of cases identified by any means (eg, radiographically with or without microscopic confirmation) in US Surveillance Epidemiology and End Results (SEER) cancer registries among 35–84-year-olds during 2004–2017 by sex and race/ethnicity using age-period-cohort (APC) models. We employed APC forecasting models to glean insights regarding the etiology, distribution, and anticipated future (2018–2027) public health impact of this neoplasm. Results In all groups, meningioma incidence overall increased through 2010, then stabilized. Temporal declines were statistically significant overall and in most groups. JoinPoint analysis of cohort rate-ratios identified substantial acceleration in White men born after 1963 (from 1.1% to 3.2% per birth year); cohort rate-ratios were stable or increasing in all groups and all birth cohorts. We forecast that meningioma incidence through 2027 will remain stable or decrease among 55–84-year-olds but remain similar to current levels among 35–54-year-olds. Total meningioma burden in 2027 is expected to be approximately 30,470 cases, similar to the expected case count of 27,830 in 2018. Conclusions Between 2004–2017, overall incidence of benign meningioma increased and then stabilized or declined. For 2018–2027, our forecast is incidence will remain generally stable in younger age groups but decrease in older age groups. Nonetheless, the total future burden will remain similar to current levels because the population is aging.

scholarly journals Impact of Fatty Acid Supplementation on Cognitive Performance among United States (US) Military Officers: The Ranger Resilience and Improved Performance on Phospholipid-Bound Omega-3’s (RRIPP-3) Study

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1854
Author(s):  
Bernadette P. Marriott ◽  
Travis H. Turner ◽  
Joseph R. Hibbeln ◽  
Jill C. Newman ◽  
Marcie Pregulman ◽  
...  
Keyword(s):  
United States ◽  
Controlled Trial ◽  
The United States ◽  
Military Officers ◽  
Krill Oil ◽  
Omega 3 ◽  
Double Blind ◽  
Significant Group ◽  
Intention To Treat ◽  
Improved Performance

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both ‘Intention to Treat’ (ITT) and ‘As Per Protocol’ (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.

scholarly journals Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Egilius L. H. Spierings ◽  
Mikko Kärppä ◽  
Xiaoping Ning ◽  
Joshua M. Cohen ◽  
Verena Ramirez Campos ◽  
...  
Keyword(s):  
United States ◽  
Czech Republic ◽  
Adverse Events ◽  
Least Squares ◽  
The United States ◽  
Inadequate Response ◽  
Double Blind ◽  
Monthly Average ◽  
Preventive Medication ◽  
Subgroup Analyses

Abstract Background The FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, particularly for patients with difficult-to-treat migraine. These prespecified subgroup analyses evaluated efficacy by country in the FOCUS study of fremanezumab in adults with episodic migraine or chronic migraine and documented inadequate response to 2 to 4 migraine preventive medication classes. Methods Overall, 838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites. For 12 weeks of double-blind treatment, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched placebo. The primary efficacy endpoint was the mean change from baseline in monthly average migraine days over 12 weeks of double-blind treatment, evaluated by country in these subgroup analyses. Results Of 14 countries contributing data, the Czech Republic (n = 188/838; 22%), the United States (n = 120/838; 14%), and Finland (n = 85/838; 10%) enrolled the most patients. Changes from baseline in monthly average migraine days over 12 weeks were significantly greater with fremanezumab versus placebo for patients in these countries: Czech Republic (least-squares mean difference versus placebo [95% confidence interval]: quarterly fremanezumab, − 1.9 [− 3.25, − 0.47]; P = 0.009; monthly fremanezumab, − 3.0 [− 4.39, − 1.59]; P < 0.001), the United States (quarterly fremanezumab, − 3.7 [− 5.77, − 1.58]; P < 0.001; monthly fremanezumab, − 4.2 [− 6.23, − 2.13]; P < 0.001), and Finland (quarterly fremanezumab, − 3.0 [− 5.32, − 0.63]; P = 0.014; monthly fremanezumab, − 3.9 [− 6.27, − 1.44]; P = 0.002). Results were comparable for the remaining 9 countries, with the least-squares mean difference versus placebo ranging from – 5.6 to – 2.4 with quarterly fremanezumab and from − 5.3 to − 1.5 with monthly fremanezumab. Incidences of serious adverse events and adverse events leading to discontinuation were low and comparable across countries and treatment groups. Conclusions Monthly and quarterly fremanezumab significantly reduced the monthly average number of migraine days versus placebo regardless of country and continent (North America versus Europe) in migraine patients with documented inadequate response to 2 to 4 migraine preventive medication classes. Trial registration ClinicalTrials.gov Identifier: NCT03308968.

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