Safety and Immunogenicity of the Ad26.RSV.preF Investigational Vaccine Coadministered With an Influenza Vaccine in Older Adults

2020 ◽  
Author(s):  
Jerald Sadoff ◽  
Els De Paepe ◽  
Wouter Haazen ◽  
Edmund Omoruyi ◽  
Arangassery R Bastian ◽  
...  
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Geometric Mean ◽  
Controlled Study ◽  
Tolerability Profile ◽  
Double Blind ◽  
Inhibition Antibody ◽  
Binding Antibody ◽  
Syncytial Virus ◽  
Significant Disease

Abstract Background Respiratory syncytial virus (RSV) and influenza cause significant disease burden in older adults. Overlapping RSV and influenza seasonality presents the opportunity to coadminister vaccines for both infections. This study assessed coadministration of the investigational vaccine, Ad26.RSV.preF, an adenovirus serotype 26 (Ad26) vector encoding RSV F protein stabilized in its prefusion conformation (pre-F), with a seasonal influenza vaccine in older adults. Methods In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control). Results The coadministration regimen had an acceptable tolerability profile. Reactogenicity was generally higher after Ad26.RSV.preF versus Fluarix, but symptoms were generally transient and mild or moderate. At 28 days after the first vaccination, the upper confidence intervals of the hemagglutination inhibition antibody geometric mean ratio (control/coadministration) for all influenza strains were <2, demonstrating noninferiority. Robust neutralizing and binding antibody responses to RSV A2 were observed in both groups. Conclusions Coadministration of Fluarix with Ad26.RSV.preF vaccine had an acceptable safety profile and showed no evidence of interference in immune response. The results are compatible with simultaneous seasonal vaccination with both vaccines. Clinical Trials Registration NCT03339713.

scholarly journals Prevention of Respiratory Syncytial Virus Infection in Healthy Adults by a Single Immunization of Ad26.RSV.preF in a Human Challenge Study

2021 ◽  
Author(s):  
Jerald Sadoff ◽  
Els De Paepe ◽  
John DeVincenzo ◽  
Efi Gymnopoulou ◽  
Joris Menten ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Controlled Study ◽  
Double Blind ◽  
Post Immunization ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is a significant cause of severe lower respiratory tract disease in children and older adults, but has no approved vaccine. This study assessed the potential of Ad26.RSV.preF to protect against RSV infection and disease in an RSV human challenge model. Methods In this double-blind, placebo-controlled study, healthy adults aged 18–50 years were randomized 1:1 to receive 1x1011 vp Ad26.RSV.preF or placebo intramuscularly. Twenty-eight days post-immunization, volunteers were challenged intranasally with RSV-A (Memphis 37b). Assesments included viral load (VL), RSV infections, clinical symptom score (CSS), safety and immunogenicity. Results Post-challenge, VL, RSV infections and disease severity were lower in Ad26.RSV.preF (n=27) versus placebo (n=26) recipients: median VL-AUC (area under the curve) qRT-PCR: 0.0 versus 236.0 (P=.012; predefined primary endpoint); median VL-AUC quantitative culture: 0.0 versus 109; RSV infections 11 (40.7%) versus 17 (65.4%); median RSV AUC-CSS 35 versus 167, respectively. From baseline to 28 days post-immunization, geometric mean fold-increases in RSV A2 neutralizing antibody titers of 5.8 and 0.9 were observed in Ad26.RSV.preF and placebo, respectively. Ad26.RSV.preF was well tolerated. Conclusions Ad26.RSV.preF demonstrated protection from RSV infection through immunization in a human challenge model, and therefore could potentially protect against natural RSV infection and disease. Clinical Trials Registration NCT03334695

scholarly journals The results of clinical trial on immunogenicity of adjuvanted quadrivalent inactivated subunit influenza vaccine Grippol Quadrivalent in pediatric population 6 to 17 years old

2020 ◽  
Vol 22 ◽  
pp. 02001
Author(s):  
O.P. Kovtun ◽  
V.V. Romanenko ◽  
I.V. Feldblum ◽  
A.U. Sabitov ◽  
A.V. Ankudinova
Keyword(s):  
Influenza Vaccine ◽  
Pediatric Population ◽  
Seroconversion Rate ◽  
Geometric Mean ◽  
Age Groups ◽  
Quadrivalent Vaccine ◽  
Seroprotection Rate ◽  
Double Blind ◽  
Care Workers ◽  
B Virus

Russian health care workers currently use trivalent influenza vaccines with a strain of a single lineage of type B virus. The purpose of our study was to evaluate the immunogenicity of an adjuvanted quadrivalent inactivated subunit influenza vaccine Grippol Quadrivalent in pediatric population 6 to 17 years old. We compared this new vaccine to a trivalent Grippol Plus vaccine in terms of immunogenicity against certain strains of influenza virus. A multicenter double-blind randomized controlled clinical study was conducted in 440 pediatric subjects (age groups: 6 to 11; 12 to 17 y.o.); 221 subjects received Grippol Quadrivalent, 219 – Grippol Plus. Vaccine immunogenicity was evaluated by seroprotection rate (SPR), seroconversion rate (SCR), geometric mean titer (GMT) of antibodies, and an X-fold rise in antibodies level (↑GMT). Antibodies quantification was done using hemagglutination inhibition assay (HAI) in serial serum dilutions. No significant differences were found between the two vaccines’ performance against A(H1N1), A(H3N2) strains or Victoria B virus. With respect to type A virus, both vaccines satisfied three of CPMP criteria (SPR, SCR, ↑GMT). With respect to Victoria B virus, the two vaccines met but one CPMP criterion (↑GMT). The immunogenicity against Yamagata B virus was evaluated only for Grippol Quadrivalent vaccine which met two of CPMP requirements (SCR, ↑GMT). Our findings suggest that in terms of its prophylactic efficiency, Grippol Quadrivalent vaccine is no inferior to the Grippol Plus one.

scholarly journals A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus

2010 ◽  
Vol 107 (19) ◽  
pp. 8800-8805 ◽  
Author(s):  
J. DeVincenzo ◽  
R. Lambkin-Williams ◽  
T. Wilkinson ◽  
J. Cehelsky ◽  
S. Nochur ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Syncytial Virus

scholarly journals A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 296
Author(s):  
Irina Kiseleva ◽  
Irina Isakova-Sivak ◽  
Marina Stukova ◽  
Marianna Erofeeva ◽  
Svetlana Donina ◽  
...  
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Phase 1 ◽  
Healthy Adults ◽  
Controlled Study ◽  
Temperature Sensitive ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Human Influenza Virus ◽  
Live Attenuated Influenza Vaccine

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

scholarly journals Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 807
Author(s):  
Mandar Jog ◽  
Jack Lee ◽  
Astrid Scheschonka ◽  
Robert Chen ◽  
Farooq Ismail ◽  
...  
Keyword(s):  
Essential Tremor ◽  
Upper Limb ◽  
Motor Performance ◽  
Controlled Study ◽  
Tolerability Profile ◽  
Double Blind ◽  
Hand Tremor ◽  
Global Impression Of Change ◽  
Amplitude Versus ◽  
Favorable Tolerability Profile

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn–Tolosa–Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, n = 19; placebo, n = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (p= 0.003) and Week 8 (p= 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (p < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (p= 0.004) and Week 8 (p < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.

scholarly journals LB2. TORC1 Inhibition with RTB101 as a Potential Pan-Antiviral Immunotherapy to Decrease the Incidence of Respiratory Tract Infections Due to Multiple Respiratory Viruses in Older Adults

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S993-S994 ◽  
Author(s):  
Joan Mannick ◽  
Amelia Tomlinson ◽  
Sarb Shergill ◽  
Grace Teo ◽  
Lloyd Klickstein
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Controlled Study ◽  
Double Blind ◽  
Increased Risk ◽  
Intent To Treat ◽  
Tract Infections ◽  
Antiviral Gene

Abstract Background Respiratory tract infections (RTIs) are a leading cause of hospitalization and death in people age ≥65 years. RTIs are caused by multiple viruses, most of which lack effective treatments. An immunotherapy that enhances pan-antiviral innate immunity may reduce RTI incidence in older adults. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was reported to upregulate pan-antiviral gene expression and protect mice from a viral RTI (York AG et al. Cell 2015). We evaluated whether TORC1 inhibition increased antiviral gene expression and decreased RTI incidence in older adults. Methods A randomized, double-blind, placebo, controlled study was conducted to determine whether the TORC1 inhibitor RTB101 alone or in combination with the TORC1 inhibitor everolimus reduced the incidence of laboratory-confirmed RTIs. The study enrolled 652 older adults at increased risk of RTI-related morbidity and mortality (defined as age ≥85 years, or age ≥65 years with asthma, COPD, type 2 diabetes mellitus, or current smokers). Subjects were treated for 16 weeks during winter cold and flu season with oral RTB101 5 mg or 10 mg once daily (QD), RTB101 10 mg twice daily, RTB101 10 mg + everolimus 0.1 mg QD, or matched placebo. The primary endpoint was the percentage of subjects with ≥1 laboratory-confirmed RTI through Week 16. Results RTB101 was well tolerated. In the intent-to-treat analysis, RTB101 10 mg QD was observed to: reduce the percentage of subjects with laboratory-confirmed RTIs by 30.6% compared with placebo (P = 0.025); reduce the incidence of RTIs caused by multiple different viruses; and upregulate interferon-stimulated pan-antiviral gene expression in whole blood (P = 0.00001 vs. placebo, Figure 1). Furthermore, RTB101 10 mg QD was observed to reduce the time to alleviation of moderate to severe RTI symptoms by 5 days, and to reduce the rate of all-cause hospitalization (rate ratio 0.439, 90% CI 0.196–0.983, P = 0.047). Conclusion RTB101 10 mg QD was associated with a significant reduction in laboratory-confirmed RTIs due to multiple viral pathogens that lack effective medicines for treatment or prevention. RTB101 was observed to upregulate interferon-stimulated pan-antiviral gene expression, which may underlie the reduction in RTI incidence. Disclosures Joan Mannick, MD, resTORbio (Employee, Shareholder), Amelia Tomlinson, PhD, resTORbio (Employee), Sarb Shergill, PhD, resTORbio (Employee), Grace Teo, PhD, resTORbio (Employee), Lloyd Klickstein, MD, PhD, resTORbio (Employee).

scholarly journals 2775. Safety and Immunogenicity of a Seasonal Influenza Vaccine and Ad26.RSV.preF Vaccine With and Without Co-Administration: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study in Adults Aged ≥ 60 Years

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S979-S979
Author(s):  
Christy Comeaux ◽  
Arangassery Rosemary Bastian ◽  
Els De Paepe ◽  
Edmund Omoruyi ◽  
Wouter Haazen ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Neutralizing Antibody ◽  
Severe Illness ◽  
Tolerability Profile ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Antibody Titers ◽  
Group 2 ◽  
Tract Infections ◽  
Group 1

Abstract Background Influenza and RSV can cause respiratory tract infections leading to severe illness, hospitalization and mortality in at-risk populations, particularly the elderly. The seasonality of influenza and RSV present the potential to co-administer vaccines. This study aimed to demonstrate the non-inferiority of co-administration of the experimental RSV vaccine Ad26.RSV.preF with an influenza vaccine (Fluarix) vs. Fluarix alone in terms of immunogenicity against influenza. Methods This was a single-center, randomized, double-blind, placebo-controlled Phase 2a study (NCT03339713) in healthy adults ≥60 years old. Volunteers were randomized 1:1 to receive Fluarix + 1 × 1011 vp Ad26.RSV.preF on Day 1 and placebo on Day 29 (Group 1), or Fluarix + placebo on Day 1 and 1 × 1011 vp Ad26.RSV.preF on Day 29 (Group 2). Blood samples were taken prior to each vaccination and at Day 57. The primary endpoints were geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibody titers against Fluarix strains (A/Michigan, A/Hong Kong, B/Brisbane and B/Phuket) and the safety and tolerability of Ad26.RSV.preF administered with or without Fluarix. A key secondary endpoint was neutralizing antibody titers to RSV A2. Results Volunteers (N = 180) were included in Group 1 (n = 90) or Group 2 (n = 90). Most volunteers were white (89%) and female (63%), with a median age of 65 years. Both groups exhibited an increase from baseline in HI antibody response on Day 29. The 95% one-sided upper confidence limit of all GMT ratios were below the non-inferiority margin of 2. The frequency of solicited adverse events (AE) after Ad26.RSV.preF vaccination was similar with and without influenza co-administration. Solicited AEs were mainly of Grade 1 and 2 and of transient duration. Most unsolicited AEs were considered unrelated to the study vaccination and were Grade 1 or 2. There were no serious AEs related to the study vaccine and there were no discontinuations due to AEs. RSV neutralizing antibody titers 29 days post- Ad26.RSV.preF immunization were similar in both groups (1404, Group 1; 1690, Group 2). Conclusion Co-administration of Ad26.RSV.preF with Fluarix was non-inferior to Fluarix alone in terms of immunogenicity against influenza and had an acceptable tolerability profile. Disclosures All authors: No reported disclosures.

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