GAP-f

30

Apr, 2021

Adequate Daclatasvir exposures in children 14-35 Kg with available adult formulations

 

Authors: Cressey RT, Abbassi M, Lallemant M, Indolfi G, Al-Nahari M, Farid S, Easterbrook P, Penazzato M,  El-Sayed HM

Published in: CROI 2021

 

Abstract: World Health Organization 2018 guidelines recommend Sofosbuvir (SOF)/Daclatasvir (DCV) as a pangenotypic regimen for the treatment of adults with chronic HCV infection. SOF/DAC is widely available as low-cost generic formulation in low and middle-income countries (LMICs). Recent studies in adolescents (?12 to <18) using SOF/DCV 400/60 mg once-daily (OD) adult dose reported excellent efficacy and safety. DCV pharmacokinetic (PK) data in younger children are lacking. Within the framework of the Global Accelerator for Pediatric Formulations (GAPf), we performed a population PK analysis using data from adolescents to predict DCV exposure in children <35 kg to determine the lowest body weight children could be treated with the available DCV formulations (60 and 30 mg).

Data from HCV-infected adolescents receiving SOF/DCV (400/60 mg, OD) who participated in a PK study in Egypt were used for PK model development. Intensive PK sampling was performed pre-dose, then 0.5, 1.0, 1.5, 2, 4, 8, 12, and 24 hrs post-dose. PK parameters were estimated using a population approach (NONMEM VII). Monte Carlo simulations were run for virtual children between 10 to <35 kg receiving 60 mg or 30 mg OD and DCV exposures (AUC0-24) were compared with the expected adults range (6.15 to 20.63 µg.hr/mL).

Seventeen HCV-infected adolescents (13 males) provided 151 DCV concentrations. Median (range) age was 14 (11-18) years and weight 50 (32-63) kg. DCV plasma concentrations were best described by a 1-compartment model with transit absorption compartments. Body weight (allometrically scaled) and albumin influenced DCV PK parameters. DCV oral clearance and volume of distribution were 7.05 L/hr/70kg and 95.8 L/70kg. In adolescents using 60 mg DCV OD, mean (SD) DCV AUC0-24, Cmax, and Clast were 12,004 (4,916) ng.hr/mL, 1,182 (393) ng/mL and 194 (168) ng/mL, respectively; while predicted to be 9,808 (3,949) ng.hr/mL, 1,039 (316) ng/mL and 148 (129) ng/mL in children 17 to <35 kg receiving 30 mg OD. Simulations showed that the proportion of children with DCV exposures above expected range rapidly increased for children <30 kg using 60 mg OD; and similarly for children 10-14 kg using 30 mg (Fig 1).

DCV 30 mg OD is expected to provide exposures comparable to adult values in children 14-35 kg. Our results suggest that children could be treated using currently available low-cost DCV formulations together with approved doses of pediatric SOF formulations, thus expanding access to HCV treatment.

 

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27

Apr, 2021

COVID-19 herd immunity by immunisation: are children in the herd?

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Authors: S. Obaro

Published in: The Lancet

 

Introduction: The scourge of COVID-19 has been global, but the most affected subgroups in the population have largely been older people and individuals with comorbid conditions that predispose them to increasingly severe disease and poor outcomes. Overall, the disease burden in children has been reasonably mild, even in those with comorbidities, such as oncological conditions. Protection from severe disease in children might be related to a lower expression of host factors required for viral replication, and to differences in the magnitude and timing of innate or adaptive immune responses. Data for recorded COVID-19 cases show that only 7% of children younger than 18 years with severe disease required intensive care, whereas 53% of adults who had severe disease required intensive care.1–3 Multisystem inflammatory syndrome in children, arguably the most dreaded presentation, typically presents between 3 and 6 weeks after SARS-CoV-2 exposure.4 Most patients at presentation have a negative nasopharyngeal RT-PCR but are positive for serology.

 

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22

Apr, 2021

ZIKAction research in the face of COVID-19

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A recollection by Isadora Siqueira, Chief Investigator of the Paediatric Registry Study, on how the ZIKAction team in Brazil adapted to the challenges brought on by COVID-19 in order to carry on with their research and recruitment into the paediatric study.

 

What impact has the COVID-19 pandemic had on ZIKAction’s study activities and what solutions has your site identified to cope with it?  

Brazil is one of the countries most affected by the COVID-19 pandemic and as of March 20th 2021, it had an incidence rate of 5,649 cases per 100,000 habitants, 4,726 cases per 100,000 women, and 1,536 per 100,000 children.

The COVID-19 pandemic significantly impacted the setup of ZIKAction Paediatric Registry in Bahia. The registry is an observational tool collecting information on children during their routine clinical care, who have been exposed to ZIKV and with congenital ZIKV. The registry will provide important information about the clinical characteristics of congenital zika infection, which will help local health professionals with these children’s clinical management. We had planned to implement the recruitment and enrolment of participants and the follow-up evaluations during the participants’ health care assistance, but with the pandemic and closure of health care institutions, we needed to find an alternative way of implementing the study.

Two things facilitated our contact with mothers of children with congenital zika and helped the recruitment process during the COVID-19 restrictions. Firstly, we hired two nurses and one physiotherapist who used to work in health services that offer public rehabilitation to the children. They had already established relationships with most of the mothers and children. They explained the study to these mothers on the phone and offered them the choice to have their children participate. The work that went into opening up recruitment into our registry was a very important activity for our region. Bahia was one of the first and most affected regions during the 2015-2016 microcephaly outbreak, with 696 cases of congenital zika infection confirmed.

Secondly, we had the support of “Abraço a Microcefalia” (Hug to Microcephaly), a community association of mothers with babies born with congenital microcephaly and other zika-related neurological issues. I used to know some of these mothers from previous studies that we conducted in 2016 and one of the nurses from our team volunteers at this association and knows most of the mothers and children. Currently, most of their children are around five years old and when the zika outbreak was ongoing, their children had more access, visibility and care. But over the years, I have witnessed how these mothers have progressively felt forgotten and invisible. They persistently struggle to ensure access to their children’s rehabilitation, a situation that got worse during the COVID-19 pandemic.

 

What is the legacy of ZIKAction in terms of improving the research capacity at your institution/country for emerging epidemics?  

ZIKAction offered an opportunity to work in a coordinated way with diverse groups of researchers from different countries and different expertise, and it also encouraged collaborative work between institutions and countries. The consortium implemented tools and built infrastructure for data collection that could be used in future epidemics. The platform with the registry database will be available even after the end of the ZIKAction project. In addition to this, our team was trained in Good Clinical Practice and General Data Protection Regulation and gained expertise in multicentric studies.

 

Has your experience in ZIKAction opened up new opportunities for you as a researcher?

As a researcher, the experience of participating in ZIKAction was amazing; it allowed me to work in collaboration with other institutions and countries and be part of a fantastic network of researchers. From this incredible experience, new opportunities are opening up, we are now involved in a recent study on COVID-19 in pregnancy and about to join the ORCHESTRA consortium, where we are going to conduct a prospective study on pregnant women with COVID-19 admitted in a local public maternity hospital, in order to characterize the COVID-19 clinical presentation in pregnant woman and also to identify the adverse outcome of their pregnancies. We are very excited to continue working in partnership with Penta.

Learn more about ZIKAction

Isadora Siqueira is a Public Health Researcher, Infectious Disease Specialist and Paediatrician at Instituto Gonçalo Moniz (FIOCRUZ) and Chief Investigator of the ZIKAction Paediatric Registry study.

21

Apr, 2021

CORONA: children and COVID-19

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An Italian-led project supported by the UniCredit Foundation to study the impact of the coronavirus on children.

The project CORONA: children and COVID-19 has kicked off. Supported by the UniCredit Foundation and led by the Penta Foundation of Padua and the One Health Center of the University of Florida, the study aims to provide the national and international scientific community with new data on the impact of the pandemic on children – from a Circular Health perspective.

Over a year since the outbreak of the SARS-CoV-2 pandemic, there is still no clear picture of children’s risk in developing symptoms, their role in transmitting the virus to adults and the long-term effects of the restrictive measures on children.

The CORONA project aims to contribute to the global scientific effort by collecting epidemiological and clinical data on children. Data collected will be used to check how often children contract the virus, as well as the way in which the disease manifests itself, develops and interacts with other diseases that may already be in progress.

The researchers also aim to identify the factors that predispose children to develop COVID-19, and how likely they are to develop it in a severe form. These data will help health authorities to plan future vaccination campaigns and, when a cure for children under 16 becomes available, to enable targeted and effective interventions.

One year after the first lockdown in Europe, the study looks to describe the psychological effects of the restrictive measures and the social distancing put in place to limit the spread of the virus on children and adolescents.

Thanks to this project, it will be possible to study the impact of COVID-19 on children, both as a direct effect of the virus but also for the effects on the psyche and on social life. We cannot continue to think in watertight compartments, but we must understand the ramifications of the pandemic event in their complexity “. Ilaria Capua, Director of One Health Center.

In short, this is a study that promises to shed light on the impact of the coronavirus on the psycho-physical well-being of children.

The project will draw from the thirty-year scientific expertise of Penta – an international network for medical research in the paediatric field, chaired by Prof. Carlo Giaquinto; and the One Health Centre – the interdisciplinary research center, directed by Prof. Ilaria Capua.

We are proud to be working with Ilaria Capua and her center of excellence in the United States and even more grateful to the UniCredit Foundation for believing in the value of this extraordinary collaboration, which will help us put children at the center of clinical research on COVID-19. As a scientific community, we have a duty to protect and support minors in this pandemic”. Carlo Giaquinto, President of the Penta Foundation.

“It is an honor for us to support the Penta Foundation of Padua and the One Health Center of the University of Florida in this important study on the pandemic impact on children. This is testament of our continued commitment to support children through the solidarity activities of UniCredit Foundation. In this last year, they have been particularly affected by COVID-19, especially as a result of the restrictions that have limited their possibility to interact, socialise and learn”. Maurizio Beretta, Chairman of the UniCredit Foundation.

The Penta Foundation will mobilize its infectious disease experts in three different European countries – that is researchers working in the United Kingdom at University College London, in Madrid at the Research Institute of the 12 de Octubre Hospital, and the Department of Women’s and Child Health at the Hospital of Padua.

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15

Apr, 2021

Abbas Lugemwa speaks on ‘PentaTr@ining Uganda 2021’

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It was a lifetime privilege and honour to host the ‘PentaTr@ining Uganda 2021′ course. This training had originally been planned for 2020, but that schedule got disrupted due to the COVID-19 pandemic. Nevertheless, we still received all the maximum support to make the course happen this year. This was a declaration of trust by Penta Foundation in the work we do as Joint Clinical Research Centre – Mbarara, and a demonstration of commitment by Penta to build capacity for excellence in research and paediatric care.
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2

Apr, 2021

Call for comments on the WHO Zika virus Research and Development Roadmap

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The WHO is calling on the public to share their comments on the newly drafted Zika virus Research and Development (R&D) Roadmap, a key component of the WHO’s R&D Blueprint which is a global strategy and preparedness plan that allows the activation of R&D activities in advance of and during pandemics. Comments can be submitted by completing this form. The Zika virus R&D roadmap aims to accelerate the development and implementation of effective medical countermeasures for the Zika virus so as to reduce morbidity, mortality and transmission of the virus. Zika is transmitted through the bite of specific species of mosquito and is known to cause birth defects and neurological problems in children born to women infected with the virus.

Currently, Zika has a low infection rate but through experience, researchers know that diseases have the tendency and capacity to re-emerge for varying reasons. The Zika outbreaks have provided researchers with a significant amount of experience which could allow public health officials to adapt timeously to future pandemics.

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