New clinical trial will assess if mpox vaccination works after virus exposure

• Research totest if post-exposure mpox shot could reduce the risk of illness and death
• Household members of mpox patients in the DRC and at-risk countries invited to take part
• Findings could help combat a large, deadly mpox outbreak affecting multiple countries in Africa

BUKAVU, DRC/ OSLO/ HAMILTON, CANADA, Jul 29- A clinical trial due to launch in the Democratic Republic of Congo (DRC) and other countries in Africa will assess whether an mpox vaccine can protect people against the disease after they have come into contact with the potentially deadly infection. 

The ‘SMART’* trial (#NCT05745987) has received US $4.9 million from CEPI and the Canadian Institutes of Health Research to find out if post-exposure vaccination of Bavarian Nordic’s MVA-BN® mpox vaccine could reduce the risk of secondary mpox cases, or, if a person contracts mpox, could reduce their severity of illness. The announcement comes on the launch of the Global Pandemic Preparedness Summit 2024, co-hosted by CEPI and partners, in Rio de Janeiro, Brazil, 29-30 July.

The evidence generated could be crucial in shaping mpox vaccination strategies to help tackle a large and deadly mpox outbreak escalating in the DRC and neighbouring countries. Over 11,000 cases and 443 deaths have been reported in the DRC so far this year, with children accounting for the majority of infections and deaths.

Led by Mark Loeb, a Professor of Pathology and Molecular Medicine with Canada’s McMaster University, the research will invite over 1500 participants (aged over 10) in households with a laboratory-confirmed mpox infection at sites in the DRC, Uganda and Nigeria to take part in the trial. The study is due to launch next month in the DRC, enrolling participants from Kamituga, South Kivu province, an area which has recently reported mpox cases.

Four weeks after participants are randomly allocated to receive either a single dose of MVA-BN or a control vaccine, scientists will compare the number of participants who contract mpox in each group. If anybody becomes sick, the researchers will conduct follow-up assessments measuring the severity of their symptoms. For example, they will look at whether a participant who received the MVA-BN®  vaccine develops fewer skin lesions than the control group and the time taken for these lesions to heal, while also monitoring hospitalisation and mortality records. 

“While healthcare workers typically vaccinate somebody before they are at risk of an infection, post-exposure-vaccinations allow for a more targeted approach, minimising use of vaccine supply. Here, individuals in high-risk groups—such as household contacts of an index case—are vaccinated to potentially reduce the risk of infection, improve survival odds and stop onward chains of transmission” said Dr Richard Hatchett, CEO of the Coalition for Epidemic Preparedness Innovations, (CEPI). “Findings from the SMART trial will provide important real-world data in local populations, including older children, that could be key to informing mpox vaccine use recommendations in endemic countries and helping to bring an end to this devastating outbreak.”

“This randomized trial will assess the effectiveness of the Bavarian Nordic smallpox vaccine in reducing the incidence of mpox and its associated complications post-exposure. This question is of paramount importance, and it needs to be addressed with the utmost urgency,” said Mark Loeb, the Principal Investigator of the trial and Canada Research Chair in Infectious Diseases.

Dr Patrick de Marie Katoto, Deputy Director of the Centre for Tropical Diseases and Global Health and Associate Professor of Clinical Epidemiology and Global Health Infection at  the Catholic University of Bukavu in the DRC, said: "SMART is so smart. This project is not just intelligent because of its acronym but also because of its strategic and impactful approach to guiding public health interventions during crises. Assessing both the safety and efficacy of Mpox vaccine in post-exposure scenarios will not only fill the current knowledge gap but also guide response strategies to save lives by protecting at-risk populations and preventing the spread of Mpox throughout the country and beyond."

The new research follows the publication of a continental plan by Africa CDC and African Ministries of Health to strengthen mpox preparedness and response efforts, as well as the World Health Organization’s (WHO) framework for enhancing prevention and control of mpox.

This is the first randomised trial to assess the potential to vaccinate high-risk individuals post mpox exposure with Bavarian Nordic’s MVA-BN® vaccine. Research has shown that a post-exposure vaccination approach with an Ebola vaccine helped substantially lower the risk of dying for people in the DRC after coming into contact with the Ebola virus.

H.E. Dr. Jean Kaseya, Director-General of Africa CDC, said: “We have seen an escalation of mpox cases in several Central and West African countries in recent months, including in the Democratic Republic of Congo. With its changing transmission dynamics, significant mortality rate, and limitations in access to countermeasures, this prolonged mpox epidemic remains a serious concern for the continent and has the potential to spread further afield. I have consistently championed the use of science and data to guide mpox response efforts and emphasized the importance of bolstering clinical trial capacity in Africa. The upcoming SMART trial demonstrates the power of scientific collaboration, which could provide important data on the potential role of post-exposure mpox vaccinations. This will help stem outbreaks both now and, in the future, strengthening preparedness and response efforts in AU member states. Africa CDC recently signed an MoU with CEPI to strengthen our partnership in the areas of research, clinical trials, and manufacturing of medical countermeasures in Africa.”

Dr. Marisa Creatore, Executive Director of the Canadian Institutes of Health Research Centre for Research on Pandemic Preparedness and Health Emergencies, co-funding the trial, said: “The CIHR Centre for Research on Pandemic Preparedness and Health Emergencies (CRPPHE) is pleased to collaborate with CEPI to support this important vaccine clinical trial, bringing together researchers from different continents for a common goal. Viruses of zoonotic origins—mpox being one of many—are an increasing global health concern and we are happy to be able to contribute to the development of new public health tools to address these concerns.”

Paul Chaplin, President and Chief Executive Officer of Bavarian Nordic, said: “We are very proud that our mpox vaccine will be used in this important post exposure clinical trial supported by CEPI and contribute to the continued efforts to provide access to a much-needed vaccine for endemic populations. Our Company is firmly committed to working with the local authorities to develop solutions for vulnerable populations to combat the ongoing mpox outbreak in the DR Congo and other countries.”

Mpox was first identified in the DR Congo in 1970. In most cases, mpox symptoms—typically fever and headache, followed by painful lesions—disappear within a few weeks. However, for some, mpox can lead to medical complications, such as bronchopneumonia, sepsis, encephalitis, loss of vision, and even death. The mpox strain behind the current outbreak, is known as Clade I. Spread through direct contact, it is estimated to be fatal in around 8-12% of cases. Experts have also noted concern for a strain known as Clade Ib fast-spreading in eastern DRC regions, including Kamituga, South Kivu, which appears to be spread through both sexual transmission and skin-to-skin contact.

CEPI and Bavarian Nordic recently announced a separate clinical trial launching in late 2024 to assess MVA-BN® in children in Africa. 

ENDS

Notes to Editors

About the SMART Trial

*The trial is named ‘Smallpox vaccine for Mpox Post-Exposure Prophylaxis: A Cluster Randomised Controlled Trial’ – or SMART for short.

CEPI is providing up to US $4.5 million in funding to the trial. CIHR is providing up to $0.4 million in funding through its Centre for Research on Pandemic Preparedness and Health Emergencies. 

The research will run as a cluster-randomised controlled trial at the Centre for Tropical Disease and Global Health, Catholic University of Bukavu in the DRC, as well as Makarere University in Uganda and multiple sites in Nigeria. The trial design may be adapted to utilise results as they accumulate. 

The SMART trial has received approval from the local Ethics board for McMaster University (Hamilton Integrated Research Ethics Board (HiREB)) and Health Canada. Ethics and regulatory approval have been gained in the DRC. Uganda and Nigeria also have ethics approval, and are awaiting regulatory approval. The WHO has provided technical inputs and endorsement of the trial protocol.

About MVA-BN

MVA-BN or Modified Vaccinia Ankara-Bavarian Nordic is a non-replicating smallpox vaccine and the only mpox vaccine approved in the U.S. and Switzerland (marketed as JYNNEOS®), Canada (marketed as IMVAMUNE®), and the EU/EEA and United Kingdom (marketed as IMVANEX®). 

Originally developed in collaboration with the U.S. government to ensure the supply of a smallpox vaccine for the entire population, including immunocompromised individuals who are not recommended vaccination with traditional replicating smallpox vaccines, MVA-BN has been indicated for use in the general adult population (18 years and older) in individuals considered at risk for smallpox or mpox infection. During the 2022-2023 mpox outbreak, the vaccine was granted an Emergency Use Authorization by the U.S. FDA for both pre- and post-exposure use in adolescents.

Bavarian Nordic has been a long-term supplier of the vaccine to the U.S. and Canada as well as several other countries as part of their national biological preparedness. During the 2022-2023 mpox outbreak, Bavarian Nordic has furthermore supported governments and supranational organizations by expanding access to the vaccine to more than 70 countries worldwide.

About CEPI 

CEPI was launched in 2017 as an innovative partnership between public, private, philanthropic and civil organisations. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of more than 50 vaccine candidates or platform technologies against multiple known high-risk pathogens or a future Disease X. Central to CEPI’s pandemic-beating five-year plan for 2022-2026 is the ‘100 Days Mission’ to compress the time taken to develop safe, effective, globally accessible vaccines against new threats to just 100 days.

About McMaster University 

McMaster is a research-intensive university ranked among the best in the world with a bold ambition to advance human and societal health and well-being. Among Canada’s top universities for student services, our research excellence is matched by our long history of teaching innovations and commitment to preparing students for an increasingly complex future. Our alumni continue to be among the most employable graduates globally, as they bring the McMaster vision of a brighter world to communities near and far.

About The Catholic University of Bukavu
The Catholic University of Bukavu, located in the Democratic Republic of Congo, is a significant educational institution that emphasizes the integration of ethical values and academic excellence. Within its framework, the Centre for Tropical Diseases and Global Health stands out as a pivotal entity. This center is dedicated to advancing research and providing training in the management and prevention of tropical diseases, as well as emerging and re-emerging diseases that are a growing concern globally. It focuses on multidisciplinary approaches to tackle health challenges, collaborating with local and international partners to enhance public health interventions. The centre's work not only contributes to scientific advancements but also plays a critical role in improving the lives of communities affected by these diseases, aligning with the university's mission of service and leadership in society.