First Report of a Phase 1 Randomised Trial of Molecular Clamp-Stabilised Spike Protein-Based and MF59-Adjuvanted Vaccine for SARS-CoV-2

2021 ◽  
Author(s):  
Keith Joseph Chappell ◽  
Francesca L. Mordant ◽  
Zheyi Li ◽  
Danushka K. Wijesundara ◽  
Paula Ellenberg ◽  
...  
Keyword(s):  
Phase 1 ◽  
Randomised Trial ◽  
Spike Protein ◽  
First Report ◽  
Adjuvanted Vaccine

scholarly journals A cluster randomised trial of strategies to increase cervical screening uptake at first invitation (STRATEGIC)

2016 ◽  
Vol 20 (68) ◽  
pp. 1-138 ◽  
Author(s):  
Henry C Kitchener ◽  
Matthew Gittins ◽  
Oliver Rivero-Arias ◽  
Apostolos Tsiachristas ◽  
Margaret Cruickshank ◽  
...  
Keyword(s):  
Discrete Choice ◽  
Choice Experiment ◽  
Phase 1 ◽  
Cervical Screening ◽  
Randomised Trial ◽  
Cost Effective ◽  
Health Technology ◽  
Cluster Randomised Trial ◽  
Phase 2 ◽  
Cluster Randomised

BackgroundFalling participation by young women in cervical screening has been observed at a time that has seen an increase in the incidence of cervical cancer in the UK in women aged < 35 years. Various barriers to screening have been documented, including fear, embarrassment and inconvenience.ObjectivesTo measure the feasibility, clinical effectiveness and cost-effectiveness of a range of interventions to increase the uptake of cervical screening among young women.DesignA cluster randomised trial based on general practices performed in two phases.SettingPrimary care in Greater Manchester and the Grampian region in Scotland.ParticipantsPhase 1: 20,879 women receiving their first invitation for cervical screening. Phase 2: 10,126 women who had not attended by 6 months.InterventionsPhase 1: pre-invitation leaflet or not, and access to online booking (Manchester only). Phase 2: (1) vaginal self-sampling kits (SSKs) sent unrequested (n = 1141); or (2) offered on request (n = 1290); (3) provided with a timed appointment (n = 1629); (4) offered access to a nurse navigator (NN) (n = 1007); or (5) offered a choice between a NN or a SSK (n = 1277); and 3782 women in control practices.Main outcome measuresUplift in screening compared with control practices, cost-effectiveness of interventions, and the women’s preferences explored in a discrete choice experiment.ResultsThe pre-invitation leaflet and offer of online booking were ineffective when compared with control practices at 3 months, 18.8% versus 19.2% [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.88 to 1.06;p = 0.485] and 17.8% versus 17.2% (OR 1.02, 95% CI 0.87 to 1.20;p = 0.802), respectively. The uptake of screening at 3 months was higher among previously human papillomavirus (HPV)-vaccinated women than unvaccinated women, 23.7% versus 11% (OR 2.07, 95% CI 1.69 to 2.53;p < 0.001). Among non-attenders, the SSK sent intervention showed a statistically significant increase in uptake at 12 months post invitation, 21.3% versus 16.2% (OR 1.51, 95% CI 1.20 to 1.91;p = 0.001), as did timed appointments, 19.8% versus 16.2% (OR 1.41, 95% CI 1.14 to 1.74;p = 0.001). The offer of a NN, a SSK on request, and a choice between timed appointments and NN were ineffective. Overall, there was a gradual rather than prompt response, as demonstrated by uptake among control practices. A discrete choice experiment indicated that women invited who had not yet attended valued the attributes inherent in self-sampling. The health economic analysis showed that both timed appointments and unsolicited SSK sent were likely to be cost-effective at a cost per quality-adjusted life-year (QALY) gained of £7593 and £8434, respectively, if extended across the national 25-year-old cohort throughout the duration of screening. The certainty of these being cost-effective at a ceiling ratio of £20,000 per QALY gained was > 90%.ConclusionWomen receiving their initial screening invitation frequently delay taking up the offer and the net impact of interventions was small. Timed appointments and SSKs sent to non-attenders at 6 months are likely to be a cost-effective means of increasing uptake and should be considered further. HPV vaccination in the catch-up programme was associated with an increased uptake of cervical screening. Future work should focus on optimising self-sampling in terms of age range, timing of offer for non-attenders and use of urine testing instead of vaginal samples.Trial registrationCurrent Controlled Trials ISRCTN52303479.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 68. See the NIHR Journals Library website for further project information.

Prospective phase 1 study assessing feasibility of IMRT and IGART to deliver simultaneous integrated high-dose tumor boost (up to 70 Gy) for the radical treatment of localized muscle-invasive bladder cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 307-307
Author(s):  
Shaista Hafeez ◽  
Karole Warren-Oseni ◽  
Helen McNair ◽  
Vibeke Hansen ◽  
Fiona McDonald ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Dose Escalation ◽  
Normal Tissue ◽  
Cone Beam Ct ◽  
Phase 1 ◽  
Randomised Trial ◽  
Late Toxicity ◽  
High Dose ◽  
Normal Bladder ◽  
Muscle Invasive

307 Background: Advances in IGART offer individualized solutions to improve target coverage and reduce normal tissue irradiation allowing opportunity to increase radiation tumour dose and spare normal bladder. Methods: A library of 3 IMRT plans were created (small, medium and large) from planning CT scans performed at 30 and 60 minutes; treating whole bladder to 52 Gy and tumour to 70 Gy in 32 fractions. Where normal tissue dose constraints were not met consideration was made to boosting tumour to lower dose (68 Gy-64 Gy). Cone beam CT (CBCT) imaging was performed prior to each fraction. Appropriate PTV was selected from the library for treatment delivery. Post treatment CBCT was acquired weekly in order to assess intra-fraction filling and coverage. Results: 22 patients have been planned using this technique. All have met tissue constraints for treatment to 70 Gy. 21 patients have completed radiotherapy, 18 completed treatment to 70 Gy; 1 patient was planned and treated to 68 Gy prior to dose escalation using this technique; 1 patient was treated to a total dose of 65.6 Gy because dose limiting toxicity occurred before dose escalation. 572 CBCTs have been evaluated. Treatment was delivered using small, medium, and large plans in 35%, 52%, and 13% cases respectively. Mean intra-fraction filling was 14 cm3 (SD 16.3, range 0.23-107.9). Mean time between pre- and post-CBCTs was 13 min (SD 2.1, range 9-18). Mean D 98% as assessed on post-radiotherapy CBCT was 98.7% (SD 1.78, range 89.9-100%). At median follow-up of 8 months (range 1-24 months), 18 patients remain alive and disease free. 2 superficial recurrences and 3 deaths from metastatic bladder cancer have occurred. No muscle invasive recurrences have occurred within this cohort. Using this technique one patient has experienced late toxicity (grade 3 cystitis) 5.3 months after radiotherapy (now resolved). Conclusions: IGART using IMRT to delivery a simultaneous integrated tumour boost is feasible with acceptable toxicity. Trial recruitment continues at 70 Gy and will be evaluated in a randomised trial (RAIDER). Clinical trial information: NCT01124682.

scholarly journals Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

2020 ◽  
Vol 383 (24) ◽  
pp. 2320-2332 ◽  
Author(s):  
Cheryl Keech ◽  
Gary Albert ◽  
Iksung Cho ◽  
Andreana Robertson ◽  
Patricia Reed ◽  
...  
Keyword(s):  
Phase 1 ◽  
Spike Protein

scholarly journals A concept analysis of ‘trial recruitment’ using the hybrid model – Phase 1 findings

2020 ◽  
Vol 3 ◽  
pp. 92
Author(s):  
Hannah Delaney ◽  
Declan Devane ◽  
Andrew Hunter ◽  
Shaun Treweek ◽  
Nicola Mills ◽  
...  
Keyword(s):  
Hybrid Model ◽  
Phase 1 ◽  
Randomised Trial ◽  
Time Frame ◽  
Concept Analysis ◽  
Operational Definition ◽  
International Committee ◽  
Trial Recruitment ◽  
Start Date ◽  
Definition Of

Background: The International Committee of Medical Journal Editors (ICMJE) requires trials submitted for publication to be registered before enrolment of the first participant; however, there is ambiguity around the definition of recruitment and in anchoring the trial start date, end date, recruitment and enrolment, temporally to trial processes. There is potential for variation in how recruitment is reported and understood in trial protocols and trial reports. We report on Phase 1 of a concept analysis of ‘trial recruitment’ and develop a preliminary operational definition of ‘trial recruitment’. Methods: A concept analysis using the hybrid model. We searched randomised and non-randomised trial reports published between January 2018 and June 2019. Included studies were sourced from the five top journals in the category of medicine with the highest impact factor. We examined how recruitment was defined temporally to four time points; screening, consent, randomisation, and allocation. Results: Of the 150 trial reports analysed, over half did not identify a clear time point of when recruitment took place in relation to any of screening/consent/randomisation/allocation. The majority of the assessed trials provided a time frame in relation to the trial (i.e. start/end date), the process that this time frame referred to differed between studies. There was variation across studies in the terminology used to describe entry to the trial and often multiple terms were used interchangeably. Conclusion: There is ambiguity around temporal descriptions of ‘trial recruitment’ in health care journals. Informed by the findings of Phase 1, we developed a preliminary temporal operational definition of trial recruitment based on i) trial recruitment of an individual or cluster and ii) the trial recruitment period. In Phase 2 this definition will be discussed in focus groups with healthcare workers involved in designing/implementing/reporting on trials; to contribute to the final phase (analytical phase) of this concept analysis.

Phase 1 dose escalation study of AQ4N, a selective hypoxic cell cytotoxin, with fractionated radiotherapy (RT): First report

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 2091-2091
Author(s):  
A. Benghiat ◽  
W. P. Steward ◽  
P. M. Loadman ◽  
M. Middleton ◽  
D. Talbot ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Hypoxic Cell ◽  
Dose Escalation Study ◽  
First Report ◽  
Fractionated Radiotherapy

scholarly journals 325 Immunotherapy with B cell activating antibody CPI-006 in patients (pts) with mild to moderate COVID-19 stimulates anti-SARS-CoV-2 antibody response, memory B cells and memory T effector cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A351-A351
Author(s):  
Gerard Criner ◽  
Mehrdad Mobasher ◽  
Craig Hill ◽  
Shenshen Hu ◽  
Suresh Mahabhashyam ◽  
...  
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
Phase 1 ◽  
Memory B Cells ◽  
Spike Protein ◽  
Effector Memory ◽  
Delayed Response ◽  
List Type ◽  
Duration Of Symptoms ◽  
Phase 1 Trial

BackgroundCD73 is present on subsets of B and T cells and is involved in lymphocyte activation. CPI-006 is a humanized IgG1, Fcγ receptor deficient anti-CD73 that has agonistic properties. In vitro studies and ongoing cancer clinical trials show that CPI-006 binds to B cells leading to expression of CD69, trafficking to lymph nodes, immunoglobulin class switching, transformation to plasmablasts and generation of memory B cells[1]. Recently, a patient in the cancer trial with asymptomatic COVID-19 developed high titers of neutralizing anti-SARS-CoV-2 antibodies following administration of CPI-006. A phase 1 trial in COVID-19 was initiated to evaluate the use of CPI-006 to enhance anti-viral immune response (NCT04464395).MethodsSingle intravenous dose escalation with N=5 per cohort of 0.3, 1.0, 3.0 and 5.0 mg/kg. Pt eligibility included PCR positive nasal swab for COVID-19; hospitalized with O2 saturation of ≥92% on <5 l/min of O2. Pts received standard care for COVID-19. Pts were monitored for safety, COVID-19 symptoms, inflammatory markers and anti-SARS-CoV-2 antibodies by ELISA. Immunophenotyping of blood by flow cytometry was performed.Results10 pts have been treated in the first 2 cohorts; median age 64 (range 28–76) and all had comorbidities: diabetes (4), hypertension (2), obesity (7) and/or cancer (2). Median duration of symptoms prior to CPI-006 was 8 days (range 1–21 days). No treatment-related adverse events were reported. There was no correlation between duration of symptoms and baseline anti-viral titers. Kinetics of anti-SARS-CoV-2 response to spike protein are shown for 7 pts with follow-up ≥ 7 days post CPI-006 (figure 1). One pt with lymphopenia (600/mm3) had delayed response to CPI-006; all other pts generated antibody response by Day 7 post-CPI-006 to both spike and RBD. Increasing titers of IgG and IgM antibodies were observed out to 28 days post treatment. In one pt examined, memory B cells increased from 1.81% to 4.83% of B cells 28 days after treatment with serum IgG titers to spike and to RBD of >1:50,000. 2 of 2 pts had increase in both CD4 and CD8 T effector memory cells at day 28. All pts were discharged (median 4 days) with clinical improvement.Abstract 325 Figure 1Antibody responses to SARS-CoV-2 spike protein in patients treated with CPI-006ConclusionsCPI-006 is well tolerated in COVID-19 pts. Low baseline titers of antibodies to virus were increased following CPI-006 in all treated pts. Immunomodulation with CPI-006 represents a novel therapy for COVID-19 aimed at stimulating more robust and prolonged anti-SARS-CoV-2 immunity potentially after infection or with vaccination.Trial RegistrationNCT04464395Ethics ApprovalThe study was approved by Temple University Hospital’s Ethics Board, Western IRB, approval number 1-1317457-1.ReferenceLuke J, Powderly J, Merchan J, Barve M, Hotson A, Mobasher M, Kwei L, Luciano G, Buggy J, Piccione E, Miller R. Immunobiology, preliminary safety, and efficacy of CPI-006, an anti-CD73 antibody with immune modulating activity, in a phase 1 trial in advanced cancers. J Clin Oncol 2019; 37:15 suppl, 2505.

scholarly journals Oral MucoRice-CTB vaccine for safety and microbiota-dependent immunogenicity in humans: a phase 1 randomised trial

2021 ◽  
Author(s):  
Yoshikazu Yuki ◽  
Masanori Nojima ◽  
Osamu Hosono ◽  
Hirotoshi Tanaka ◽  
Yasumasa Kimura ◽  
...  
Keyword(s):  
Phase 1 ◽  
Randomised Trial
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