Dataset Information

Safety, tolerability and immunogenicity of the ExPEC4V (JNJ-63871860) vaccine for prevention of invasive extraintestinal pathogenic Escherichia coli disease: A phase 1, randomized, double-blind, placebo-controlled study in healthy Japanese participants.

ABSTRACT: This Phase 1, randomized, double-blind, placebo-controlled study was conducted to evaluate the safety, tolerability and immunogenicity of different doses of ExPEC4V conjugate vaccine (4-16µg Polysaccharide [PS]/serotype) in healthy Japanese participants, stratified into younger (?20 to <50 years) or older age groups (?50 years). Within each age group, participants were randomized to a single vaccination with 1 of 3 dose levels of ExPEC4V (4, 8 and 16 µg PS/serotype) or placebo. Safety and tolerability were the primary objectives; immunogenicity was secondary. Of the 48 participants, 47 (98%) completed; one (2%) in the placebo group discontinued. A total of 48% participants had ?1 AE (younger group: n = 13 [54%]; older group: n = 10 [41.7%]). Solicited and unsolicited AEs were reported in 44% and 8% participants, respectively in the combined ExPEC4V groups. Pain/tenderness (n = 11 [31%]) and redness (n = 9 [25%]) were the most frequently reported solicited local AEs, whereas fatigue (n = 4 [11%]), headache (n = 4 [11%]), muscle pain (n = 2 [6%]), and malaise (n = 5 [14%]) were the most common solicited systemic AEs in the combined ExPEC4V group. No serious AEs, deaths, or discontinuation due to AEs were reported. All doses were immunogenic with an increase in IgG (ELISA) geometric mean titers of at least 5-fold from baseline to Days 15 and 30 for all serotypes. Of participants vaccinated with ExPEC4V, 75% - 100% demonstrated an ELISA titer increase of ?2-fold. Strong correlation observed between ELISA and OPK. ExPEC4V was well tolerated and elicited an immunogenic response at all dose levels (up to 16 µg PS/serotype) in healthy Japanese participants.

SUBMITTER: Inoue M

PROVIDER: S-EPMC6183137 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety, tolerability and immunogenicity of the ExPEC4V (JNJ-63871860) vaccine for prevention of invasive extraintestinal pathogenic Escherichia coli disease: A phase 1, randomized, double-blind, placebo-controlled study in healthy Japanese participants.

Inoue Megumi M Ogawa Tetsuro T Tamura Hiroshi H Hagiwara Yosuke Y Saito Yuki Y Abbanat Darren D van den Dobbelsteen Germie G Hermans Peter P Thoelen Stefan S Poolman Jan J Ibarra de Palacios Patricia P

Human vaccines & immunotherapeutics 20180628 9

This Phase 1, randomized, double-blind, placebo-controlled study was conducted to evaluate the safety, tolerability and immunogenicity of different doses of ExPEC4V conjugate vaccine (4-16µg Polysaccharide [PS]/serotype) in healthy Japanese participants, stratified into younger (≥20 to <50 years) or older age groups (≥50 years). Within each age group, participants were randomized to a single vaccination with 1 of 3 dose levels of ExPEC4V (4, 8 and 16 µg PS/serotype) or placebo. Safety and tolera ...[more]

PMID: 29771596

Similar Datasets

Project description:BACKGROUND:Immunotherapy targeting the amyloid-? (A?) peptide is a promising strategy for the treatment of Alzheimer's disease (AD); however, none of the active or passive vaccines tested have been demonstrated to be effective to date. We have developed the first active vaccine against the C-terminal end of A?40, ABvac40, and assessed its safety and tolerability in a phase I clinical trial. METHODS:A randomised, double-blind, placebo-controlled, parallel-group, phase I study of ABvac40 was conducted with patients aged 50-85 years with mild to moderate AD. Participants were entered into three separate groups according to time of study entry and were randomly allocated to receive ABvac40 or placebo (overall ratio 2:1). The first group received two half-doses of ABvac40 or placebo, whereas the second and third groups received two and three full doses, respectively. All treatments were administered subcutaneously at 4-week intervals. Patients, carers and investigators were blind to treatment allocation throughout the study. The primary objective was to assess the safety and tolerability of ABvac40 by registering all adverse events (AEs). All patients who received at least one dose of treatment were included in the safety analysis. The secondary objective was to evaluate the immunogenicity of ABvac40 by titration of specific anti-A?40 antibodies in plasma. RESULTS:Twenty-four patients were randomly allocated: 16 patients to the ABvac40 group and 8 patients to the placebo group. All randomised patients completed the study, therefore the intention-to-treat and safety populations were identical. Overall, 71 AEs affecting 18 patients were recorded: 11 (69%) in the ABvac40 group and 7 (88%) in the placebo group (p?=?0.6214). Neither incident vasogenic oedema nor sulcal effusion (amyloid-related imaging abnormalities corresponding to vasogenic oedema and sulcal effusions) nor microhaemorrhages (amyloid-related imaging abnormalities corresponding to microhaemorrhages and hemosiderin deposits) were detected throughout the study period in the ABvac40-treated patients. Eleven of 12 (~92%) individuals receiving three injections of ABvac40 developed specific anti-A?40 antibodies. CONCLUSIONS:ABvac40 showed a favourable safety and tolerability profile while eliciting a consistent and specific immune response. An ongoing phase II clinical trial is needed to confirm these results and to explore the clinical efficacy of ABvac40. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03113812 . Retrospectively registered on 14 April 2017.

Project description:BackgroundMultiple vaccine candidates against COVID-19 are currently being evaluated. We evaluate the safety and immunogenicity protein of a novel SARS-CoV-2 virus receptor-binding domain (RBD) vaccine.MethodsA phase 1-2, randomised, double-blind, placebo-controlled trial was carried out in "Saturnino Lora" Hospital, Santiago de Cuba, Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1:1, in blocks) to three groups: placebo, 25 µg and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0·5 mL in the deltoid region. During the first phase, two immunization schedules were studied: 0-14-28 days (short) and 0-28-56 days (long). In phase 2, only the short schedule was evaluated. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained masked during the study period. The main endpoints were safety and the proportion of subjects with seroconversion of anti-RBD IgG antibodies, analysed by intention to treat and per protocol, respectively. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000346.FindingsBetween Dec 7, 2020, and Feb 9, 2021, 792 subjects were included; 132 (66 in each vaccination schedule, divided into 22 for each group) in phase 1, and 660 (220 in each group plus 66 from the short scheme of phase 1) in phase 2. The product was well tolerated. No severe adverse events were reported. During phase 1, the incidence of adverse events in the 25 µg, 50 µg, and placebo arms for the short schedule were 6/22 (27·3%), 6/22 (27·3%), 3/22 (13·6%), respectively, and for the long schedule were 8/22 (36·4%), 9/22 (40·9%), 4/22 (18·2%), respectively. In phase 2, adverse reactions were reported by 53/242 (21·9%), 75/242 (31·0%) and 41/242 (16·9%) participants in the 25 µg, 50 µg, and placebo group, respectively. Adverse reactions were minimal, mostly mild, and from the injection site, which resolved in the first 24-48 hours. In phase 1, seroconversion at day 56 was seen in 95·2% of the participants (20/21) in the 50 μg group, 81% (17/21) in the 25 μg group, and none in the placebo group (0/22). For the long schedule, seroconversion at day 70 was seen in 100% of the participants (21/21) in the 50 μg group, 94·7% (18/19) in the 25 μg group, and none in the placebo group (0/22). In phase 2, seroconversion of anti-RBD IgG antibodies at day 56 was seen in 89·2% of the participants in the 50 μg group (214/240; 95% CI 84·5-92·82), 77·7% in the 25 μg group (185/238; 72·0-82·9) and 4·6% in the placebo group (11/239; 2·3-8·1). Compared with the placebo arm, the differences in the proportion of participants with seroconversion were 73·1% (95% CI 66·8-79·5) and 84·6% (79·4-89·7) in the 25 μg and 50 μg groups, respectively. The seroconversion rate in the 50 μg group was significantly higher than in the 25 μg group (p=0·0012).InterpretationThe Abdala vaccine was safe, well tolerated, and induced humoral immune responses against SARS-CoV-2. These results, in the context of the emergency COVID-19 pandemic, support the 50 μg dose, applied in a 0-14-28 days schedule, for further clinical trials to confirm vaccine efficacy.FundingCentre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

Project description:Abstract Background A vaccine developed to prevent invasive extraintestinal pathogenic Escherichia coli disease (IED) is being evaluated in a phase 3 clinical trial (NCT04899336). However, historical performance of similar clinical trials has been challenged by inefficient endpoint catchment. Here we report the EXPECT-1 (NCT04087681) study findings on the capture techniques for IED and hospital admissions in a community-based setting. Methods EXPECT-1 was a prospective, observational study conducted in networks of 8 hospitals with surrounding primary care centers in North America, Europe, and Asia. Participants were followed for 1 year to track hospital admissions and occurrence of IED as reported by the primary care physician (PCP) or the participant. In 151 US participants, a geofence technology was used to track admissions to hospital areas. Participants were eligible if aged ≥ 60 years and if they did not have severe chronic conditions. Data were collected from October 24, 2019 until January 28, 2021. Study outcomes included incidence of IED and the rate of hospital admission. Results In total, 4470 participants were enrolled: 68% were female, 74.4% were white, median age was 70 years, and 59.4% had a urinary tract infection (UTI) in the past 10 years. Four IED events were captured with a cumulative incidence (95% CI) of 0.09% (0.024–0.229%) and an incidence rate of 98.6 cases (25.6–248.4) per 100,000 person-years. The incidence increased to 0.15% (0.041–0.385%) and 164.4 (43.8–420) per 100,000 person-years among participants with a history of UTI. Of the 4 IED events, 2 were participant self-reports, 1 PCP report, and 1 report via follow-up phone call. Of all hospital admissions, 56.6% were captured by PCPs and 48.7% by participants’ self-reports. The Kappa statistic varied from 0.31–0.65, indicating fair to moderate agreement between PCP reports and participant self-reports. Geofencing captured 99% of > 800 entries and exits from hospital areas. Conclusion The findings suggest that older adults with a history of UTI in the past 10 years may be a good target population for an efficacy clinical investigation on IED. PCP reports, participant self-reports, and geofencing can be promoted to track study endpoints in a community-based clinical trial setting. Disclosures Joachim Doua, MD, MPH, Janssen: Employee|Janssen: Stocks/Bonds Stephen Ruhmel, MPH, Janssen: Employee Oscar Go, PhD, Janssen: Employee of Janssen Research & Development LLC. Ranee Chatterjee, MD, MPH, Bristol Myers Squibb: Grant/Research Support|Epigenomics: Grant/Research Support|Verily: Grant/Research Support Michal Sarnecki, MD, Janssen: Employee|Janssen: Stocks/Bonds Jan Poolman, PhD, Janssen: Janssen Vaccines & Prevention B.V.|Janssen: Stocks/Bonds Marc Bonten, MD, PhD, Astra-Zeneca: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Novartis: Advisor/Consultant.

Dataset Information

Safety, tolerability and immunogenicity of the ExPEC4V (JNJ-63871860) vaccine for prevention of invasive extraintestinal pathogenic Escherichia coli disease: A phase 1, randomized, double-blind, placebo-controlled study in healthy Japanese participants.

Publications

Safety, tolerability and immunogenicity of the ExPEC4V (JNJ-63871860) vaccine for prevention of invasive extraintestinal pathogenic Escherichia coli disease: A phase 1, randomized, double-blind, placebo-controlled study in healthy Japanese participants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets