Periodic Reporting for period 6 - EBOVAC2 (Development of a Prophylactic Ebola Vaccine Using an Heterologous Prime-Boost Regimen: Phase II - Sofia ref.: 115861)
Periodo di rendicontazione: 2020-01-01 al 2021-05-31
Combining the expertise and capabilities of global research institutions, non-government organizations and the pharmaceutical industry has been critical to help address the Ebola public health challenge.
The Ebola vaccine projects - EBOVAC1, EBOVAC2, EBOVAC3, EBODAC and EBOMAN - are a series of clinical trials and associated projects which aim to assess a novel two-dose preventive vaccination regimen against Ebola Virus Disease (EVD). These projects are part of the IMI Ebola+ programme that was launched in response to the Ebola virus disease (EVD) outbreak that started in western Africa in 2014. The comprehensive programme includes 12 projects and contributes to efforts to tackle a wide range of challenges in Ebola research, including vaccines development, clinical trials, storage and transport, and diagnostics.
In this context, EBOVAC2 is responsible for conducting Phase 2 clinical trials in Europe and Africa to assess the safety, tolerability and immunogenicity (immune response) of the two-dose vaccination regimen (Ad26.ZEBOV and MVA-BN-Filo) in development by Janssen Vaccines & Prevention B.V. part of the Janssen Pharmaceutical Companies of Johnson & Johnson. The vaccine regimen involves an initial dose that stimulates the immune system to develop disease-specific antibodies, followed by a second dose two months later with the goal of potentially strengthening and optimizing the duration of immunity.
EBOVAC2 completed this Phase 2 clinical work as well as some exploratory research aimed at better understanding the immune response to the vaccine and its underlying mechanisms.
The Ebola vaccine projects - EBOVAC1, EBOVAC2, EBOVAC3, EBODAC and EBOMAN - are a series of clinical trials and associated projects which aim to assess a novel two-dose preventive vaccination regimen against Ebola Virus Disease (EVD). These projects are part of the IMI Ebola+ programme that was launched in response to the Ebola virus disease (EVD) outbreak that started in western Africa in 2014. The comprehensive programme includes 12 projects and contributes to efforts to tackle a wide range of challenges in Ebola research, including vaccines development, clinical trials, storage and transport, and diagnostics.
In this context, EBOVAC2 is responsible for conducting Phase 2 clinical trials in Europe and Africa to assess the safety, tolerability and immunogenicity (immune response) of the two-dose vaccination regimen (Ad26.ZEBOV and MVA-BN-Filo) in development by Janssen Vaccines & Prevention B.V. part of the Janssen Pharmaceutical Companies of Johnson & Johnson. The vaccine regimen involves an initial dose that stimulates the immune system to develop disease-specific antibodies, followed by a second dose two months later with the goal of potentially strengthening and optimizing the duration of immunity.
EBOVAC2 completed this Phase 2 clinical work as well as some exploratory research aimed at better understanding the immune response to the vaccine and its underlying mechanisms.
EBOVAC2 has implemented two phase 2 trials in clinical sites in Europe and Africa. The Phase 2 trials were planned to start as soon as preliminary safety data from the EBOVAC1 Phase 1 trials in the UK and Africa became available. Sites in the UK, France and Africa started enrolment in 2015.
In 2016, the Phase 2 trial in the EU progressed well and enrolment was completed. EBL2002 study was conducted at Kenya, Uganda, Cote d'Ivoire and Burkina Faso. At the end of 2016, enrolment of healthy adults was nearly complete and the team opened enrolment of HIV+ adults and children in 2017. Also in 2016, the results of the early response to the vaccine regimen became available in a subset of participants in the European trial (Cohort 1, UK). The consortium also contributed to the Central Information Repository that hosts information assets and project documentation from IMI Ebola+ projects.
In 2017 and 2018, the work proceeded as planned, finalising the enrolment of volunteers, performing sophisticated immunologic analyses and preparing clinical data for use in regulatory documents. In 2018, only Cohort 3 (children ages 4-11 years) and the 90 volunteers who agreed to participate in the booster dose sub-study were still in the final follow-up stage in Africa. For all other cohorts volunteers had entered the long-term safety extension study (outside the scope of EBOVAC2). Preliminary safety and core immunogenicity results of both Phase 2 studies became available and were presented to the European and African Principal Investigators at the end of 2018. A workshop on vaccine clinical trial methodology was successfully organized in Burkina Faso for West African young medical researchers in January 2018.
In 2019, EBOVAC2 duration was extended following our second project review recommendations. The focus turned towards preparing regulatory documents, clinical study reports and publications for EBL2001 and EBL2002. The results of the core analysis were presented at the IMI Annual Meeting in Nairobi. The exploratory work was continued in 2019 notably on the cellular response to vaccination in B cell and NK cell). Data centralization allowed for the integrative statistical analyses to be performed to further develop mathematical models of infectious diseases to gain understanding of complex systems and provide a framework for making predictions and projections under different scenarios.
In 2020, EBOVAC2 finalized the remaining exploratory work and complete the publications of the core trials and the immune response research. EBOVAC2 organized a final meeting at the end of this last period with a specific Stakeholder Meeting which presented the results obtained to a panel of more than 120 key opinion leaders involved in the development of Ebola vaccines in Europe, the USA and in Africa on June 22nd, 2021.
This occasion allowed the members of the EBOVAC projects to share the lessons learned from the trials implementation, present the projects main achievements and discuss global strategies to respond to the challenges brought not only by Ebola, but also by other emerging diseases.
In 2016, the Phase 2 trial in the EU progressed well and enrolment was completed. EBL2002 study was conducted at Kenya, Uganda, Cote d'Ivoire and Burkina Faso. At the end of 2016, enrolment of healthy adults was nearly complete and the team opened enrolment of HIV+ adults and children in 2017. Also in 2016, the results of the early response to the vaccine regimen became available in a subset of participants in the European trial (Cohort 1, UK). The consortium also contributed to the Central Information Repository that hosts information assets and project documentation from IMI Ebola+ projects.
In 2017 and 2018, the work proceeded as planned, finalising the enrolment of volunteers, performing sophisticated immunologic analyses and preparing clinical data for use in regulatory documents. In 2018, only Cohort 3 (children ages 4-11 years) and the 90 volunteers who agreed to participate in the booster dose sub-study were still in the final follow-up stage in Africa. For all other cohorts volunteers had entered the long-term safety extension study (outside the scope of EBOVAC2). Preliminary safety and core immunogenicity results of both Phase 2 studies became available and were presented to the European and African Principal Investigators at the end of 2018. A workshop on vaccine clinical trial methodology was successfully organized in Burkina Faso for West African young medical researchers in January 2018.
In 2019, EBOVAC2 duration was extended following our second project review recommendations. The focus turned towards preparing regulatory documents, clinical study reports and publications for EBL2001 and EBL2002. The results of the core analysis were presented at the IMI Annual Meeting in Nairobi. The exploratory work was continued in 2019 notably on the cellular response to vaccination in B cell and NK cell). Data centralization allowed for the integrative statistical analyses to be performed to further develop mathematical models of infectious diseases to gain understanding of complex systems and provide a framework for making predictions and projections under different scenarios.
In 2020, EBOVAC2 finalized the remaining exploratory work and complete the publications of the core trials and the immune response research. EBOVAC2 organized a final meeting at the end of this last period with a specific Stakeholder Meeting which presented the results obtained to a panel of more than 120 key opinion leaders involved in the development of Ebola vaccines in Europe, the USA and in Africa on June 22nd, 2021.
This occasion allowed the members of the EBOVAC projects to share the lessons learned from the trials implementation, present the projects main achievements and discuss global strategies to respond to the challenges brought not only by Ebola, but also by other emerging diseases.
The risk to global public health posed by the Ebola virus was reinforced in 2018, when the Democratic Republic of the Congo (DRC) experienced two unrelated outbreaks of the disease. The second outbreak, which began in August 2018 only days after the first was declared over and has continued into 2019, is now the second biggest recorded outbreak of Ebola. More recently, in early 2021, another limited outbreak took place in Guinea and DRC, the 12th outbreak for this later country since 1976.
Such a significant threat requires a long-term commitment, including implementation of surveillance systems, rapid response preparedness and the development and availability of effective vaccines. EBOVAC2 aims to provide the data to establish the safety and immunogenicity of a novel 2-dose vaccine regimen.
On 6 November 2019 Janssen submitted two MAAs to EMA for the 2-dose Ebola vaccine regimen Ad26.ZEBOV MVA-BN-Filo (one for each vaccine). EMA granted accelerated review (September 2019). Discussions for a biologics license application (BLA) filing for the Janssen vaccine regimen are ongoing with the U.S. Food and Drug Administration (FDA). Rwanda granted the vaccine regimen conditional approval under exceptional emergency in September 2019. Since then, EMA granted the MAA on July 1st, 2020. At the March 2021 SAGE meeting, the interim recommendations on the use of the heterologous two-dose Ebola vaccine regimen was reconfirmed, which then made possible World Health Organization (WHO) Prequalification (PQ) for the Ebola vaccine regimen.
Currently, Janssen is collaborating with the WHO to enable registration of the Ebola vaccine regimen in African countries. On 4 Jun 2021, SAGE published their Ebola vaccination strategies that in the presence of an outbreak the vaccine should be given to people living in affected areas and those living in neighboring areas but who are not eligible for Merck’s vaccine and, in the absence of an outbreak the vaccine could be proposed to national response teams, International responders, laboratory workers with possible exposure to Ebola virus and those working in specialized research units and Ebola Treatment Units. At this stage, large scale preventive vaccinations in the absence of an outbreak is not yet recommended, showing the necessity to continue research on the vaccine.
Finally, the lessons learned from this project will have a positive impact on global strategies to develop vaccines quickly in situations of public health emergencies, thereby helping to improve the world's preparedness for emerging infectious diseases.
Such a significant threat requires a long-term commitment, including implementation of surveillance systems, rapid response preparedness and the development and availability of effective vaccines. EBOVAC2 aims to provide the data to establish the safety and immunogenicity of a novel 2-dose vaccine regimen.
On 6 November 2019 Janssen submitted two MAAs to EMA for the 2-dose Ebola vaccine regimen Ad26.ZEBOV MVA-BN-Filo (one for each vaccine). EMA granted accelerated review (September 2019). Discussions for a biologics license application (BLA) filing for the Janssen vaccine regimen are ongoing with the U.S. Food and Drug Administration (FDA). Rwanda granted the vaccine regimen conditional approval under exceptional emergency in September 2019. Since then, EMA granted the MAA on July 1st, 2020. At the March 2021 SAGE meeting, the interim recommendations on the use of the heterologous two-dose Ebola vaccine regimen was reconfirmed, which then made possible World Health Organization (WHO) Prequalification (PQ) for the Ebola vaccine regimen.
Currently, Janssen is collaborating with the WHO to enable registration of the Ebola vaccine regimen in African countries. On 4 Jun 2021, SAGE published their Ebola vaccination strategies that in the presence of an outbreak the vaccine should be given to people living in affected areas and those living in neighboring areas but who are not eligible for Merck’s vaccine and, in the absence of an outbreak the vaccine could be proposed to national response teams, International responders, laboratory workers with possible exposure to Ebola virus and those working in specialized research units and Ebola Treatment Units. At this stage, large scale preventive vaccinations in the absence of an outbreak is not yet recommended, showing the necessity to continue research on the vaccine.
Finally, the lessons learned from this project will have a positive impact on global strategies to develop vaccines quickly in situations of public health emergencies, thereby helping to improve the world's preparedness for emerging infectious diseases.