Periodic Reporting for period 3 - TherVacB (THERVACB: A THERAPEUTIC VACCINE TO CURE HEPATITIS B)
Periodo di rendicontazione: 2023-01-01 al 2024-06-30
TherVacB aims to develop a therapeutic vaccine to cure patients living with chronic hepatitis B (CHB). According to WHOs Global Hepatitis Report 2024 an estimated 254 million people are living with hepatitis B and there are about 1.1 million deaths each year from the sequelae. To generate 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.
The robust TherVacB management and coordination framework has been implemented for thorough risk assessment and changes to the work plan timelines as well as overall leadership of scientific activities and clinical trial planning.
Targeted communication and awareness campaigns were carried out in close collaboration with key stakeholders in the project networks. The public website, available in seven languages, features news posts about joint workshops and events, up-to-date information for patient communities, key publications of relevance to TherVacB, the series of HBV Cure FAQ community videos.
Regulatory control and approval aspects of the clinical trial have been continuously addressed, monitored, and coordinated with a focus in this period on: Finalization of the key documents for the clinical trial application (CTA), i.e. clinical trial protocol, investigator’s brochure and investigational medicinal product dossiers. The CTA was submitted via the CTIS portal and approval obtained without any additional requests.
Extension of the stability of all TherVacB vaccine components was achieved in the ongoing stability programs. The current shelf-life of the vaccine components last at least until month 36 and ensures the dosing during the extended project duration.
The European HBV Patient Registry has been further expanded, with now six actively recruiting sites in Germany, Spain, and Italy and two additional sites in the UK that will include patients in the further course of the project.
Up to now a total of 328 have been enrolled in the patient registry, of which 52 patients fulfilled the inclusion criteria for the TherVacB clinical trial. The expansion of the infrastructure and the extension of the laboratory at the African partner site in Tanzania were completed. All processes, including the most important virological and immunological endpoint assays, have been implemented, validated and continuously quality checked and form the basis for the successful implementation and completion of the clinical trial at the African partner site. The study protocol for the HBV screening cohort received ethics approval and the set up of the patient cohort will start in October 2024.
A study on patient recruitment provides first-of-its-kind empirical data on the factors influencing the acceptance of social media recruitment for clinical studies among Hepatitis B patients in Germany. Findings are informative for clinical researchers who are considering recruiting hard-to-reach patient populations via social media.
The baseline set of all necessary study documentation in accordance with all legal and the relevant regulatory guidelines for GCP are in place. The eCRF was developed and optimised and introduced to the initial trial sites. The safety management and the statistical analysis plan are available as well as the data management and data validation plan. All study-relevant documents are collected in the clinical trial master file (CTMF) and for each site in the investigator site file. An updated version of the data management plan was released for the use by the consortium. The data and safety management board (DSMB) was activated including the selection of its chair and the approval of the DSMB charta.
The clinical supplier was mandated for labelling (multi-language), packaging, intermediate storage and shipment of the study medication of TherVacB to the respective clinical trial sites. Study medication for the initial study arms is ready for shipment.
All immune monitoring processes are running and subject to continuous internal and external quality control. Innovative immunoassays to clinically validate novel potential biomarker candidates have been established and the final fit-for-purpose validation is about to be finalized. A GCP-compliant database in which all results of the virological and immunological endpoint analyses can be accessed has been established and is ready for use.
Targeted communication and awareness campaigns were carried out in close collaboration with key stakeholders in the project networks. The public website, available in seven languages, features news posts about joint workshops and events, up-to-date information for patient communities, key publications of relevance to TherVacB, the series of HBV Cure FAQ community videos.
Regulatory control and approval aspects of the clinical trial have been continuously addressed, monitored, and coordinated with a focus in this period on: Finalization of the key documents for the clinical trial application (CTA), i.e. clinical trial protocol, investigator’s brochure and investigational medicinal product dossiers. The CTA was submitted via the CTIS portal and approval obtained without any additional requests.
Extension of the stability of all TherVacB vaccine components was achieved in the ongoing stability programs. The current shelf-life of the vaccine components last at least until month 36 and ensures the dosing during the extended project duration.
The European HBV Patient Registry has been further expanded, with now six actively recruiting sites in Germany, Spain, and Italy and two additional sites in the UK that will include patients in the further course of the project.
Up to now a total of 328 have been enrolled in the patient registry, of which 52 patients fulfilled the inclusion criteria for the TherVacB clinical trial. The expansion of the infrastructure and the extension of the laboratory at the African partner site in Tanzania were completed. All processes, including the most important virological and immunological endpoint assays, have been implemented, validated and continuously quality checked and form the basis for the successful implementation and completion of the clinical trial at the African partner site. The study protocol for the HBV screening cohort received ethics approval and the set up of the patient cohort will start in October 2024.
A study on patient recruitment provides first-of-its-kind empirical data on the factors influencing the acceptance of social media recruitment for clinical studies among Hepatitis B patients in Germany. Findings are informative for clinical researchers who are considering recruiting hard-to-reach patient populations via social media.
The baseline set of all necessary study documentation in accordance with all legal and the relevant regulatory guidelines for GCP are in place. The eCRF was developed and optimised and introduced to the initial trial sites. The safety management and the statistical analysis plan are available as well as the data management and data validation plan. All study-relevant documents are collected in the clinical trial master file (CTMF) and for each site in the investigator site file. An updated version of the data management plan was released for the use by the consortium. The data and safety management board (DSMB) was activated including the selection of its chair and the approval of the DSMB charta.
The clinical supplier was mandated for labelling (multi-language), packaging, intermediate storage and shipment of the study medication of TherVacB to the respective clinical trial sites. Study medication for the initial study arms is ready for shipment.
All immune monitoring processes are running and subject to continuous internal and external quality control. Innovative immunoassays to clinically validate novel potential biomarker candidates have been established and the final fit-for-purpose validation is about to be finalized. A GCP-compliant database in which all results of the virological and immunological endpoint analyses can be accessed has been established and is ready for use.
The close collaboration between TherVacB partners, project networks and external stakeholders, specifically experienced patient organisations and advocacies, for targeted hepatitis B and D awareness or communication about the TherVacB Patient Registry, clear community-relevant information about the start of the TherVacB clinical trial or workshops with other consortia have sustained the high visibility of the TherVacB project via a range of project channels. Communication measures have proven to be highly effective in reaching especially CHB patients. A large and growing number of people living with CHB / HBV in nearly 100 countries are reaching out directly to the project (https://www.thervacb.eu/patients/patients-contact-us/(si apre in una nuova finestra)) asking for the TherVacB cure or about participation in the TherVacB clinical trial. The project’s efforts to maintain a trustful bilateral exchange with every contact also functions as a pre-selection for recruitment into the TherVacB Patient Registry.
Building up a common registry of hepatitis B patients across Europe, whose virological and host parameters have been determined, will be instrumental for a seamless transition from phase 1b/2a clinical trial to further clinical trials. Based on the results from this clinical trial, selection of patients for therapeutic vaccination according to improved stratification criteria can then occur for the first time from suitable patient groups within this registry built across Europe. The successful capacity building at the Tanzanian partner site of the perfect basis to allow expansion of the TherVacB trial sites in other African countries for future clinical trials.
With the established infrastructure and documentation of all study relevant documents and analysis plans the basis for completing the study and achieve all related project goals is set. Further, large parts of this infrastructure form the basis for the further clinical development of TherVacB until market approval. The newly developed cytokine secretion assay (CSA) is a robust and time-saving immunological endpoint assay to predict treatment efficacy which can be easily performed in a decentralized manner at the TherVacB clinical trial sites.
Building up a common registry of hepatitis B patients across Europe, whose virological and host parameters have been determined, will be instrumental for a seamless transition from phase 1b/2a clinical trial to further clinical trials. Based on the results from this clinical trial, selection of patients for therapeutic vaccination according to improved stratification criteria can then occur for the first time from suitable patient groups within this registry built across Europe. The successful capacity building at the Tanzanian partner site of the perfect basis to allow expansion of the TherVacB trial sites in other African countries for future clinical trials.
With the established infrastructure and documentation of all study relevant documents and analysis plans the basis for completing the study and achieve all related project goals is set. Further, large parts of this infrastructure form the basis for the further clinical development of TherVacB until market approval. The newly developed cytokine secretion assay (CSA) is a robust and time-saving immunological endpoint assay to predict treatment efficacy which can be easily performed in a decentralized manner at the TherVacB clinical trial sites.