Health Equity in Pediatric Drug Development: Translating Aspiration into Operation.
Authors: Folayan MO, Conway M, Russo C, Diniz N, Jafta LP, Sam-Agudu NA, Bernays S, Santana VM, Epps C, Turner MA.
Published in: Springer Nature
Authors: Folayan MO, Conway M, Russo C, Diniz N, Jafta LP, Sam-Agudu NA, Bernays S, Santana VM, Epps C, Turner MA.
Published in: Springer Nature
The Penta ID Network Meeting 2022 (PIM, 28-30 April 2022) gave our members – the Penta family – a great opportunity to meet face-to-face, after more than two years of distance due to the COVID-19 pandemic.
The beautiful Sorrento in Italy set the stage for three days of talks, discussions, debates, and social activities (including a visit to nearby Pompei and a historical restaurant in the city).
Over the years, PIM has strengthened the connections between collaborating institutions, industries, and international organizations associated with the Penta ID Network. These connections have helped propel our research portfolio and fuelled innovation in our key scientific areas.
Discussions during PIM 2022 focused on the Penta ID Network’s activities in the areas of HIV, Hepatitis B and C, COVID-19, ZIKV/arboviruses, fungal infections, infections in pregnancy and other recently developed Penta projects and plans. Recent data about new antivirals, antimicrobials, and vaccines were also presented and so were some sessions dedicated to antimicrobial resistance and the future of real-world data in research.
Children are at the centre of everything we do. So at PIM 2022, two members of our Youth Trials Board, a group of young people who participate in our paediatric clinical trials as partners and advisors, were involved in the debates around the importance of research and gave the Network a unique perspective on what clinical research means to them. Additionally, the Early Career Researchers of the Penta ID Network presented their plans for fostering the work of young scientists with the support of Penta.
We are sure that the PIM 2022 will result in many new partnerships, collaborations, projects, and opportunities for future work in Penta!
Involving patients in our clinical trials is of utmost importance to us. Penta is dedicated to ensuring that the young people in our trials are included at various stages of the research process. In late April 2022, Mercy Shibemba, one of our PPI experts, sat down with two members of our Youth Trials Board (YTB) to talk about the work that they do and what it’s like to participate in clinical trials as young people living with HIV.
What do you do as part of the Youth Trials Board?
“A few weeks ago, me and a couple of other young people went on a training with the MRC CTU. The researchers had to step down from professionalism and explain what they do in a simple way. In one activity, they had to simplify some statistics for us. I think they found it quite interesting although some of them struggled a little because they weren’t used to using simple words. It was a good experience.”
You asked them about dolutegravir and pharmacokinetics and all of these things that sound like big concepts but are part of our daily lives. How did it feel to speak to the people that work on these trials from your perspective as “this is my lived experience”?
“It was really fun, because this time we finally got to see what happens behind the scenes. So, it was really interesting, and it was nice seeing the people that basically helped us get to the point where we at are now, and a wall broke down, it was a nice experience.”
So my next question is why is the work that you and the other young people do as part of YTB so important? Why is it needed?
“I think it’s really important because many young people in clinical trials don’t know that researchers care about them. So, it’s a good way for us to come together and share what we’ve done with the researchers and help them realize that they’re cared about.”
We recently had a look at a Patient Information sheet. Can we talk a bit about how you felt? I remember both of you saying you wish you had something you could understand rather than something adults knew that you couldn’t understand
“I read about a sentence and then I just couldn’t do anymore, it made no sense. In clinical trials we sign over the rights to our information and I feel we need to understand it. It should be something simpler, with a few words in a context we can understand.”
“I feel like I got tricked, because it’s full of words we can’t even understand. I feel like if it’s given to us, it’s given to us to read. So it should be simpler.”
So the next question is about looking to the future. Based on your experiences and what you’ve learnt, how would you like young people to be included moving forward?
“I think one of the main things is to keep involving young people so we can share our perspective. It’s nice that researchers come and explain to young people what’s going on and the young people tell the researchers what’s going on in their lives as well.”
“I think it would be nice if us as young people involved in trials got regular updates. Just being able to have the results as a child would make you feel better and make you feel more included in the process.”
The work that we’ve done together on the youth trials board means that we’ve been able to simplify those messages. One of the things that has really blown me away while working with the Youth Trial Boards is how many times you all ask about feedback and making sure you get that loop of updates about how your voices and opinions influence trials and just my encouragement to everyone working in with children in clinical trials not to forget to update us because we always want to know what is going on.
Visit our Patient Involvement page to learn more about how Penta is engaging with young people in clinical trials
Penta was highly represented at the Mini-Symposium hosted by Green Templeton College – University of Oxford on the 7th of April 2022 entitled “Serving the children of the world: examining the current research needs in Paediatrics”.
The key idea of the symposium was exploring the needs of child health globally and acknowledging the importance of facilitating research collaboration in global health. The topics of the symposium spanned from Perinatal Medicine to Adolescent Health. World class speakers from all over the world as well as students from Oxford, contributed towards making this symposium a success. Partnering organisations, were The Global Heath Network, the European Society for Paediatric Research (ESPR) and the Academic Paediatrics Society (APA, UK). With their support, we were able to compile an outstanding programme.
The valuable experience of the Penta consortium on patient involvement was presented by Mercy Shibemba, an award-winning activist. Using her story of growing up with HIV to educate, challenge and inspire she presented how research should ensure that the voices of young people are central in decisions and processes that impact their lives. The title of her presentation was: “Challenge or opportunity? Utilising the voices of children to shape paediatric research”.
Prof Carlo Giaquinto presented the experience of Penta in dealing with the dynamic evolution of paediatric infectious diseases research, highlighting the essential role of global collaborations.
Speakers and participants engaged in a valuable debate around the challenges and needs of child health globally acknowledging the importance of synergies and ac collaborations in global health in paediatrics. Overall, the mini symposium was extremely successful from various perspectives. The high-level interventions showed how crucial is to have an interdisciplinary approach to global child health. The day was an opportunity to create new collaborations that will for sure generate new opportunities of research for young researchers.
Thank you to Davide Bilardi, Senior Project manager at Penta and all those involved in organising this symposium for an insightful afternoon.
On 12 May, a Rapid Communication on the reported increase of acute hepatitis of unknown origin in children was published in Eurosurveillance. The paper outlines the extent and geographical distribution of these unexplained paediatric hepatitis cases in Europe and beyond. It also highlights the challenges of drawing comparisons against a baseline of a syndrome which is not under systematic surveillance and has no standard case definitions in place.
Acute hepatitis of unknown origin is a rare paediatric syndrome, which causes severe inflammation of the liver and may require transplantation. Lately, multiple countries have reported an increasing number of children acquiring this rare form of hepatitis. In early May, the UK International Health Regulations National Focal Point reported 163 cases, 11 of which required liver transplants. According to the European Centre for Disease Prevention and Control, at the end of April, approximately 55 cases were reported from 12 EU countries, 12 cases from the United States, 12 from Israel, and 1 from Japan.
Penta was among a group of European clinical trial networks and paediatric gastroenterology and infectious diseases societies that contributed to data collection by developing and distributing a rapid online survey to Penta ID Network members. The survey aimed to quickly assess the extent, geographical distribution and potential aetiology of the outbreak in Europe in the first four months of 2022, compared to the incidence rates in the previous 5 years. Participating hospitals were asked to report the number of possible, probable, and severe possible and probable cases according to case definitions. 52 hospitals in 17 European and 7 non-European countries responded to the survey, 13 of which were liver transplantation centres.
Compared with previous years, the incidence of paediatric cases of probable acute hepatitis of unknown origin appears to be higher in 5 out of 17 surveyed European countries and 1 out of 7 non-European countries, the UK seeming particularly affected. Adenovirus has been identified as a possible causative agent, with possible co-factors being the lack of prior adenovirus exposure because of COVID-19 public health measures, co-infection with SARS-CoV-2 or other pathogen, or a toxin, drug, or environmental exposure.
The Rapid Communication provides insight in the form of current ‘best available evidence’. However, additional epidemiological and clinical investigations are needed to establish if there is an excess of acute hepatitis cases of unknown origin in children, which would require targeted studies to determine its cause. Penta remains available to support this process. We thank all the members who contributed to the data collection by filling in the survey.
Read the Rapid Communication here.
One of the objective of RBDCOV is to test whether the vaccine can reactivate or re-generate a protective immune response against the virus
The RBDCOV project, in which Penta is a partner, started a Phase III clinical trial of the Covid-19 vaccine in immunocompromised people, after the Spanish Agency for Medicines and Health Products (AEMPS) authorised it on 9 May. This clinical trial will determine whether an additional dose of HIPRA’s Covid-19 vaccine can generate an immune response in people living with immune system disorders, such as immunodeficiencies or who are receiving immunosuppressant treatments. For this reason, we will study whether the vaccine is capable of reactivating or generating a sufficient immune response again, increasing the activity of the immune system (natural defences) against the virus. The safety of the new vaccine and whether it can prolong the effect of the vaccination that the participants have already received will also be studied.
The study will involve 400 volunteers from three hospitals in Spain and three hospitals in Turkey. These are adults with pathologies or immunosuppressive conditions whose immune system may be less responsive to vaccines. The profiles of the study participants include people with primary immunodeficiency including HIV; those who have received a kidney transplant or have kidney disease; people on a dialysis programme, and people who are receiving treatment with Rituximab (a medication used to treat certain autoimmune diseases).
This clinical trial, led by HIPRA – a Spanish multinational pharmaceutical and biotechnology corporation, is carried out in the framework of the European-funded RBDCOV project, which also includes clinical studies with children and adolescents.
As of 29 March 2022, HIPRA is immersed in the rolling review process of the European Medicines Agency (EMA), which consists of the evaluation of existing data on the HIPRA vaccine as they are generated until marketing authorisation, as per the usual standards of the European Union about efficacy, safety, and quality. HIPRA expects to receive conditional marketing authorisation in mid-2022. The company is already prepared at the production level to have the vaccine available in a few days.
Details on the HIPRA vaccine
The Covid-19 vaccine developed by HIPRA is a bivalent, adjuvanted recombinant protein vaccine based on a receptor-binding domain (RBD) fusion heterodimer containing the B.1.1.7 (Alpha) and B. 1.351 (Beta) variants of SARS-CoV-2.
HIPRA’s vaccine works by preparing the body to defend itself against COVID-19. It contains two versions of part of the spike protein, or spike, which have been produced in the laboratory: one version corresponds to part of the alpha variant spike protein and the other corresponds to the beta variant spike protein. This protein is found on the surface of SARS-CoV-2 and is used by the virus to enter cells in the body. The vaccine also contains an adjuvant, a substance that helps boost immune responses to the vaccine.
When a person receives the vaccine, their immune system identifies the two vaccine proteins as foreign and produces natural defenses (antibodies and T-cells) against them. If the vaccinated person later encounters SARS-CoV-2, the immune system will recognise the herringbone protein of the virus and be ready to attack it. Antibodies and immune cells can protect against COVID-19 by working together to kill the virus, prevent it from entering the body’s cells and destroy infected cells.
The HIPRA vaccine is kept at refrigerated temperatures between 2 and 8°C, facilitating storage and distribution. The technology used allows great versatility to adapt it to new variants of the virus, if necessary, in the future. The results obtained show that a booster dose of HIPRA generates an immune response equal to or greater than that generated with a booster dose of Comirnaty against the Beta, Delta, and Omicron variants, which suggests a high capacity for protection against the disease.
More on the RBDCOV project
RBDCOV is one of 11 selected projects supporting clinical trials of the new vaccine that can reach beyond Europe’s borders by creating links with other European initiatives to address the fight against the coronavirus crisis and strengthen existing research infrastructures. The European Commission has selected 11 projects in total involving 312 research teams from 40 countries. These projects fall under the Horizon Europe Framework Programme (2021-2027), Europe’s largest research and innovation programme, and one of its priorities is to support urgent research on coronavirus and its variants.
Visit the project website for more about RBDCOV.
By design, capacity building is a fundamental part of the UNIVERSAL project. The aim of the project’s capacity building activities are to improve the ability of African and European young investigators in designing and conducting clinical trials. As such, the project conducted a Training Needs Assessment (TNA) from March 17th to June 21st 2021 among 108 African early career researchers from Cameroon, Mali, Senegal, Uganda and Zimbabwe who are involved in the project (see fig 1 below).
A TNA is the process of collecting and analysing data to determine what training is needed to improve individuals’ performances and what should be taught. Within the scope of HIV treatment and prevention, particularly paediatric HIV, specific skills and knowledge are imperative for maximising the reach and impact of slowing down the spread and elimination of HIV.
“We believe that for effective and sustainable capacity building, there is need to identify training priorities, and tailor the capacity building activities to individual, as well as institutional capacity building needs. The UNIVERSAL training needs survey provided insight into the priority training needs of participants from various UNIVERSAL sites, which is enabling the project team to focus the capacity building activities, making the training relevant and responsive to participants, needs.” Pauline Amuge, UNIVERSAL Training and Capacity Building work package lead.
The assessment identified the top five priority training needs; research implementation, designing studies, leadership and management, grant writing, and developing research protocols.
Figure 2. Top priority capacity building needs among participants within UNIVERSAL sites in SSA
The TNA is the first step towards developing the scientific careers and skills of young clinical researchers, particularly from low middle-income countries, to improve their ability to conduct research at UNIVERSAL sites. The findings from the TNA are being used to develop a training plan focused on addressing the needs identified.
Visit the UNIVERSAL website to learn more about the project.
Authors: Beek JV, Fraaij PL, Giaquinto C, Shingadia D, Horby P, Indolfi G, Koopmans M, Acute hepatitis study group
Published in: Eurosurveillance
In 2016 the Early-treated Perinatally HIV-infected individuals: Improving Children’s Actual Life (EPIICAL) consortium began gathering scientists and clinicians specialising in paediatric HIV to work towards establishing new, scientific efforts on the early treatment of HIV to improve the lives of children and ultimately lead to the remission of HIV in children.
The main focus of the consortium was the development of a predictive platform to inform treatment strategies that would lead to HIV remission. EPIICAL 2016-2020 succeeded in designing and conducting studies on paediatric HIV which led to the development of different, well-established cohorts of children living with HIV in Europe and Africa. These cohorts were intended for the evaluation of strategies to optimise the management of perinatally HIV-infected children. During the first phase of the project, the Child and Adolescent Reservoir Measurements on early suppressive ART (CARMA) study provided a lot of information about the immunological and virological features of early treated HIV child and adolescents on long term viral control. This data highlighted the impact of early-infant treatment on limiting the reservoir size also after a decade of suppressive therapy. Moreover in this cohort it was demonstrated that the early initiation of ART preserves the functionality of immune system.
In parallel, at this stage the consortium also established a large cohort of HIV infected infants treated before 3 months of age in limited-resource settings monitoring the clinical, virological and immunological features. These children were enrolled in Early Anti-Retroviral Treatment in HIV-infected Children (EARTH) study with the aim of providing important information on the characteristics associated with the establishment of HIV reservoirs.
EPIICAL’s success from 2016 to 2020 led to the development of the second phase of the project, Novel Strategies to induce long-term viral remission in Early Treated HIV infected Children. This phase, EPIICAL 2020-2024, aims to follow up on the established cohorts from the first phase. To do this and improve the management of these patients, the consortium developed a detailed retention strategy in the context of the BESST study, based on the analysis of adherence issues with children and adolescents on antiretrovirals. In these cohorts, thanks to the introduction of innovative methods, we are identifying novel immunological and virological endpoints.
The precious and informative data produced by the CARMA study inspired a new study, CARMA Global. This study will involve children seven years and older and youth infected with HIV who started ART in the first three months of life and remained in care while on ART. Participating children would have a viral load that is less than 50 copies per ml.
EPIICAL 2016-2020 succeeded in highlighting the strong possibility that early ART initiation plays a significant role in suppressing HIV. The high-quality data generated by the consortium is vital for improving the current understanding of HIV remission while paving the way to unravel the mechanisms behind viral remission. As we are now in the third year of EPIICAL 2020-2024, and there is currently no cure for HIV, we hope that the knowledge we generate will provide a clear picture of the evolution of HIV in early treated children and that will guide a new therapeutic intervention.
EPIICAL is sponsored by Penta and funded by ViiV Healthcare.