Periodic Reporting for period 2 - TherVacB (THERVACB: A THERAPEUTIC VACCINE TO CURE HEPATITIS B)
Période du rapport: 2021-07-01 au 2022-12-31
TherVacB aims to develop a therapeutic vaccine to cure patients living with chronic hepatitis B (CHB). More than 3% of the world's population are chronically infected with the hepatitis B virus (HBV). Worldwide 880,000 humans die each year from the sequelae. To enable such cure, the consortium of leading virologists, immunologists and specialized physicians will use a newly designed vaccine as an immunotherapy. Since Africa suffers from a high infection rate, part of the clinical trial will be conducted in Tanzania – also to help building local capacities for diagnosing and treating hepatitis B. Further objectives of TherVacB are: (1) Establish a pan-European HBV patient registry (2) Develop and run an awareness campaign (3) Develop an ethically validated social media-based approach for patient information and recruitment (4) Develop novel hepatitis B biomarkers to allow an optimal prediction of the treatment response.
WP1 TherVacB Management: The operational TherVacB management and coordination framework has been refined following the 1st EC approved GA amendment.
WP2 Dissemination, Exploitation, Communication and Training: The stock of digital communication material has been enhanced for usage in targeted campaigns. The public website has been further extended and made available in a total of six clinically relevant languages now featuring key publications of relevance to TherVacB, and a growing collection of HBV Cure FAQ community videos .
WP3 Regulatory Affairs: Regulatory control and approval aspects of the clinical trial have been continuously addressed, monitored, and coordinated with a focus in this period on: (1) GMP manufacturing of TherVacB vaccine components (2) generation of clinical trial application documents (3) developing and refining the clinical trial protocol. Support from an experienced regulatory consultancy was still obtained to re-risk the program and prevent later regulatory objections.
WP4 Patient registry: new patients were included in the established European HBV Patients Registry of CHB patients, leading to a total of >190 patients included since the start of the project at five sites in Germany, Spain, and Italy. This will also be used as a basis for efficient recruitment into the upcoming TherVacB clinical trial. To support this, the eCRF was updated with defined parameters to easily identify patients qualifying for a TherVacB study participation.
WP5 Capacity Building in Tanzania: In preparation of the clinical trial and for treatment of Hepatitis B in general, capacity building has substantially advanced. The laboratory infrastructure to perform HBV-specific serology was established including validation of related tests and training of personnel. Additional diagnostic capacity to perform immunological endpoints assays was established and validated. The set-up of the patient registry has been advanced until the first ethics approval, a 2nd is still outstanding. In view of the upcoming clinical trial and recruitment planning, local governmental authorities and the Mbeya Zonal Referral Hospital were provided initial trial information. The development of the database for inclusion of patients has been started.
WP6 Ethics of Patient Recruitment: Building on a literature review, previous experiences at UKE, and together with all relevant work packages, expert and patient consultant interviews, two different approaches for social media recruitment strategies for the TherVacB clinical trial have been developed and submitted as deliverable 6.1. Results were also presented to a broader audience at conferences and online lectures. Furthermore, semi-structured interviews with 30 multidisciplinary experts and six Hepatitis B patients was conducted about the ethical, legal, social, and practical issues of social media recruitment. This has led to a survey study among Hepatitis B patients in three German hospitals to quantitatively assess the acceptance of social media recruitment and potential links to perceived stigma, privacy perceptions, and digital literacy. Data collection is ongoing.
WP8 Phase 1b/2a clinical trial: The clinical trial design was further adapted based on feedback from regulatory and latest scientific results.
WP9 Immune monitoring and biomarker identification: Setup of the central immune monitoring site have been completed. Innovative exploratory endpoints assays have been established and implemented at the different sites involved in WP9. Novel biomarkers predicting response to immune therapies are currently evaluated by members of WP9 with the aim to use these parameters for patient selection into the clinical trial and for predicting response to therapeutic vaccination during the TherVacB clinical trial.
WP2 Dissemination, Exploitation, Communication and Training: The stock of digital communication material has been enhanced for usage in targeted campaigns. The public website has been further extended and made available in a total of six clinically relevant languages now featuring key publications of relevance to TherVacB, and a growing collection of HBV Cure FAQ community videos .
WP3 Regulatory Affairs: Regulatory control and approval aspects of the clinical trial have been continuously addressed, monitored, and coordinated with a focus in this period on: (1) GMP manufacturing of TherVacB vaccine components (2) generation of clinical trial application documents (3) developing and refining the clinical trial protocol. Support from an experienced regulatory consultancy was still obtained to re-risk the program and prevent later regulatory objections.
WP4 Patient registry: new patients were included in the established European HBV Patients Registry of CHB patients, leading to a total of >190 patients included since the start of the project at five sites in Germany, Spain, and Italy. This will also be used as a basis for efficient recruitment into the upcoming TherVacB clinical trial. To support this, the eCRF was updated with defined parameters to easily identify patients qualifying for a TherVacB study participation.
WP5 Capacity Building in Tanzania: In preparation of the clinical trial and for treatment of Hepatitis B in general, capacity building has substantially advanced. The laboratory infrastructure to perform HBV-specific serology was established including validation of related tests and training of personnel. Additional diagnostic capacity to perform immunological endpoints assays was established and validated. The set-up of the patient registry has been advanced until the first ethics approval, a 2nd is still outstanding. In view of the upcoming clinical trial and recruitment planning, local governmental authorities and the Mbeya Zonal Referral Hospital were provided initial trial information. The development of the database for inclusion of patients has been started.
WP6 Ethics of Patient Recruitment: Building on a literature review, previous experiences at UKE, and together with all relevant work packages, expert and patient consultant interviews, two different approaches for social media recruitment strategies for the TherVacB clinical trial have been developed and submitted as deliverable 6.1. Results were also presented to a broader audience at conferences and online lectures. Furthermore, semi-structured interviews with 30 multidisciplinary experts and six Hepatitis B patients was conducted about the ethical, legal, social, and practical issues of social media recruitment. This has led to a survey study among Hepatitis B patients in three German hospitals to quantitatively assess the acceptance of social media recruitment and potential links to perceived stigma, privacy perceptions, and digital literacy. Data collection is ongoing.
WP8 Phase 1b/2a clinical trial: The clinical trial design was further adapted based on feedback from regulatory and latest scientific results.
WP9 Immune monitoring and biomarker identification: Setup of the central immune monitoring site have been completed. Innovative exploratory endpoints assays have been established and implemented at the different sites involved in WP9. Novel biomarkers predicting response to immune therapies are currently evaluated by members of WP9 with the aim to use these parameters for patient selection into the clinical trial and for predicting response to therapeutic vaccination during the TherVacB clinical trial.
All TherVacB-related regulatory documents generated (CTP, IB, IMPD) will form the basis for the foreseen phase 1b/2a clinical trial but also future clinical development.
The European Patient Registry will optimize inclusion of patients in the TherVacB project and other clinical trials enabling intercollaboration between centers on HBV epidemiology at a European level. This strategy will also minimize the different barriers regarding clinical trial inclusion across countries. The knowledge obtained may have an impact not only on the patients included in the registry and/or the TherVacB clinical trial but also in all patients living with hepatitis B at a European level.
HBV-specific analytical capacity has been established at the NIMR at the Mbeya site.
This establishment in NIMR-Mbeya will pave the way towards patients care and treatment in the region which subsequently will allow them to join Hepatitis B therapeutic vaccine when eligible. The treatment cost of Hepatitis B has not been piloted in the country, as no treatment is available. As the morbidity and mortality of disease has been documented, addressing it will be of great relief. During the conduct of the cohort and the clinical trial, some ideas and clues may be obtained on socio-economic implication. The initial sensitisation to the community has started at the community advisory members, and members of the ethics. This will be a advancement towards care and treatment of Hepatitis B in the region and all over the country.
The studies conducted in WP6 provide one of the first empirical assessments on the ethical and social implications of social media recruitment in clinical studies. Through publications in renowned peer-reviewed, interdisciplinary journals, we contribute to ongoing debates in bioethics regarding the use of social media for study recruitment but also provide practical considerations for researchers interested in using social media recruitment in an ethically, legally and socially acceptable manner.
Social media have been discussed to improve cost-effectiveness and recruitment accrual. The study conducted by TUM-MED offers a more fine-grained analysis on what factors to consider when evaluating whether or not to use social media for clinical study recruitment. Social media offer possibilities for both private and public communication among patients, researchers and between the two groups. The study analyses these possibilities and their ethical, legal, and social implications, suggesting that social media can be very helpful in specific cases but the exact execution of such an exchange needs to be carefully planned in a context-specific manner.
The European Patient Registry will optimize inclusion of patients in the TherVacB project and other clinical trials enabling intercollaboration between centers on HBV epidemiology at a European level. This strategy will also minimize the different barriers regarding clinical trial inclusion across countries. The knowledge obtained may have an impact not only on the patients included in the registry and/or the TherVacB clinical trial but also in all patients living with hepatitis B at a European level.
HBV-specific analytical capacity has been established at the NIMR at the Mbeya site.
This establishment in NIMR-Mbeya will pave the way towards patients care and treatment in the region which subsequently will allow them to join Hepatitis B therapeutic vaccine when eligible. The treatment cost of Hepatitis B has not been piloted in the country, as no treatment is available. As the morbidity and mortality of disease has been documented, addressing it will be of great relief. During the conduct of the cohort and the clinical trial, some ideas and clues may be obtained on socio-economic implication. The initial sensitisation to the community has started at the community advisory members, and members of the ethics. This will be a advancement towards care and treatment of Hepatitis B in the region and all over the country.
The studies conducted in WP6 provide one of the first empirical assessments on the ethical and social implications of social media recruitment in clinical studies. Through publications in renowned peer-reviewed, interdisciplinary journals, we contribute to ongoing debates in bioethics regarding the use of social media for study recruitment but also provide practical considerations for researchers interested in using social media recruitment in an ethically, legally and socially acceptable manner.
Social media have been discussed to improve cost-effectiveness and recruitment accrual. The study conducted by TUM-MED offers a more fine-grained analysis on what factors to consider when evaluating whether or not to use social media for clinical study recruitment. Social media offer possibilities for both private and public communication among patients, researchers and between the two groups. The study analyses these possibilities and their ethical, legal, and social implications, suggesting that social media can be very helpful in specific cases but the exact execution of such an exchange needs to be carefully planned in a context-specific manner.