Ian Hirsch
A5004267401- Asthma and respiratory diseases
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Respiratory and Cough-Related Research
- Eosinophilic Esophagitis
- Vaccine Coverage and Hesitancy
- Allergic Rhinitis and Sensitization
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Systems, Economic Evaluations, Quality of Life
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Statistical Methods in Clinical Trials
- Inhalation and Respiratory Drug Delivery
- Musculoskeletal pain and rehabilitation
- IL-33, ST2, and ILC Pathways
- Meta-analysis and systematic reviews
- COVID-19 epidemiological studies
- Pharmacovigilance and Adverse Drug Reactions
- Urticaria and Related Conditions
- Respiratory viral infections research
- Pain Management and Placebo Effect
- SARS-CoV-2 detection and testing
- COVID-19 and Mental Health
- Pediatric health and respiratory diseases
- Occupational exposure and asthma
- Heparin-Induced Thrombocytopenia and Thrombosis
AstraZeneca (United States)
2015-2024
AstraZeneca (United Kingdom)
2010-2024
Immune Regulation (United Kingdom)
2024
AstraZeneca (Singapore)
2021-2023
University of Rochester
2021
Unity Health System
2021
Columbia University
2021
Johns Hopkins University
2021
University of Maryland, Baltimore
2021
Walter Reed Army Institute of Research
2021
SummaryBackgroundA safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of COVID-19 pandemic. We evaluated safety efficacy ChAdOx1 nCoV-19 in a pooled interim analysis four trials.MethodsThis includes data from ongoing blinded, randomised, controlled trials done across UK, Brazil, South Africa. Participants aged 18 years older were randomly assigned (1:1) or (meningococcal group A,...
The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given an interval 4-12 weeks. planned roll-out in will involve vaccinating people high-risk categories their first dose immediately, delivering second 12 weeks later. Here, we provide both further prespecified pooled analysis trials exploratory analyses impact on immunogenicity efficacy extending...
Abstract The global supply of COVID-19 vaccines remains limited. An understanding the immune response that is predictive protection could facilitate rapid licensure new vaccines. Data from a randomized efficacy trial ChAdOx1 nCoV-19 (AZD1222) vaccine in United Kingdom was analyzed to determine antibody levels associated with against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after second dose were measured infected noninfected recipients. Higher all markers correlated reduced...
BackgroundThe safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection United States, Chile, Peru has not been known.MethodsIn this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated safety, efficacy, immunogenicity two doses as compared with placebo preventing onset symptomatic disease 2019 (Covid-19) 15 days or more...
Benralizumab is an anti-eosinophilic monoclonal antibody that reduces exacerbations and improves lung function for patients with severe, uncontrolled asthma eosinophilic inflammation. We evaluated the impact of baseline factors on benralizumab efficacy severe asthma. This analysis used pooled data from SIROCCO ( ClinicalTrials.gov identifier NCT01928771 ) CALIMA NCT01914757 Phase III studies. Patients aged 12–75 years receiving high-dosage inhaled corticosteroids plus long-acting β 2...
Abstract Background Although 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16 th June 2021, global supply remains limited. An understanding immune response associated with protection could facilitate rapid licensure new vaccines. Methods Data from a randomised efficacy trial ChAdOx1 nCoV-19 (AZD1222) vaccine in UK was analysed to determine antibody levels against SARS-CoV-2. Anti-spike and anti-RBD IgG multiplex immunoassay, pseudovirus live neutralising at 28...
Patients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody indicated for add-on maintenance treatment of patients aged 12 years and older, phenotype.To investigate the efficacy benralizumab by atopic status serum immunoglobulin E (IgE) concentrations.We analyzed pooled results from SIROCCO (NCT01928771) CALIMA (NCT01914757) phase III studies. to 75 old severe, uncontrolled on high-dosage inhaled...
Several vaccine candidates to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or disease 2019 (COVID-19) have entered will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials. To facilitate harmonized evaluation and comparison of the efficacy these vaccines, a general set endpoints is proposed, along with considerations guide selection primary on basis statistical reasoning. The plausibility that protection symptomatic...
Background Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated patients severe, uncontrolled asthma. Methods Data were pooled from seven similarly designed phase II III randomised controlled trials of biologic therapies for the treatment that enrolled comparable patient populations. Annualised rates (AAERs) placebo assessed by baseline characteristics, biomarker concentrations at...
In the phase 3 trial of AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates risk protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses negative participants based on case-cohort sampling recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The...
Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting β2-agonists (ICS/LABA), significantly reduced asthma exacerbations, improved lung function, symptoms for patients severe, uncontrolled blood eosinophil counts ≥300 cells/μL the Phase III SIROCCO CALIMA studies. To understand efficacy safety of benralizumab eosinophil-driven disease lower than 300 cells/μL, we evaluated effect applying cutoff ≥150 cells/μL.Adult...
For patients with eosinophilic asthma allergic characteristics, understanding the key drivers of exacerbations is important to identify optimal treatment strategies. Benralizumab an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that significantly reduces exacerbation frequency for severe, uncontrolled asthma. We evaluated predictive value baseline blood eosinophil counts vs. serum immunoglobulin E (IgE) concentrations on risk and association these variables benralizumab...
Importance Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders. Objective To identify associated with COVID-19, severe SARS-CoV-2 infection. Design, Setting, Participants This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, vaccine efficacy trials harmonized protocols established by the Prevention Network. Individual-level from participants randomized to receive...
Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, MHRA, with a regimen of two standard doses given an interval between 4 and 12 weeks. planned rollout in will involve vaccinating people high risk categories their first dose immediately, delivering second weeks later.Here we provide both further prespecified pooled analysis trials exploratory analyses impact on immunogenicity efficacy extending priming booster doses. In...
The minimum clinically important difference (MCID) between treatments is recognized as a key concept in the design and interpretation of results from clinical trial. Yet even assuming such can be derived, it not necessarily clear how should used. In this paper, we consider three possible roles for MCID. They are: (1) using MCID to determine required sample size so that trial has pre-specified statistical power conclude significant treatment effect when equal MCID; (2) requiring with high...
Fixed airflow obstruction (FAO) is associated with severe eosinophilic asthma. Benralizumab an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody for patients severe, uncontrolled asthma.We evaluated FAO influence on benralizumab treatment response.We performed a post hoc analysis of pooled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) data asthma baseline blood eosinophil counts 300 or more cells/μL who received 30 mg every 8 weeks placebo. Demographics, clinical...
BackgroundWhile vaccines have established utility against COVID-19, phase 3 efficacy studies generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective of SARS-CoV-2 and COVID-19 early in pandemic over three-to six-month follow-up compared with...
To evaluate the efficacy, tolerability, and safety of multiple fixed dosages esreboxetine for treatment fibromyalgia.Patients meeting American College Rheumatology criteria fibromyalgia were randomized to receive at 4 mg/day (n=277), 8 (n=284), or 10 (n=283) matching placebo (n=278) 14 weeks. The primary efficacy outcomes weekly mean pain score Fibromyalgia Impact Questionnaire (FIQ) total week 14. Secondary measures included scores Patient's Global Impression Change (PGIC) scale, Fatigue...
BackgroundBlood eosinophil count (BEC) measurements are a noninvasive, relatively reliable surrogate marker for eosinophilic airway inflammation. Single of peripheral BEC greater than or equal to 150 cells/μL predict the response anti-eosinophil therapies patients with characteristics severe asthma.ObjectiveTo describe how BECs shift over time severe, uncontrolled asthma receiving placebo in 2 large, randomized, placebo-controlled clinical trials benralizumab (SIROCCO and CALIMA).MethodsOur...
BackgroundThe stability and variability of blood eosinophil counts (BECs) to phenotype patients with severe asthma is not fully understood.ObjectiveThis post hoc, longitudinal, pooled analysis placebo-arm from 2 phase 3 studies evaluated the clinical implications BEC in moderate-to-severe asthma.MethodsThis included SIROCCO CALIMA who received maintenance medium- high-dosage inhaled corticosteroids plus long-acting β2-agonists; 2:1 BECs 300 cells/μL or higher less than were enrolled. The...