Periodic Reporting for period 1 - INTEGRATE (The Integrate study : An adaptive platform trial for the development of a new intervention to combat Lassa fever in Africa)
Okres sprawozdawczy: 2023-07-01 do 2024-12-31
Lassa fever (LF) is an acute febrile illness caused by Lassa virus (LASV) and associated with bleeding, organ failure, and shock. Each year, over 900,000 people are infected with the Lassa fever virus in Benin, Guinea, Liberia, Nigeria, Sierra Leone and Togo. Nigeria is the country by far most affected by LF in the world with about 80% of global cases.
Transmitted from contact with certain rats or from person to person through infected body fluids, LF virus acts with devastating speed, killing people within 10 days of their first symptoms if not correctly treated.
The current standard of care for LF is ribavirin but is associated with important toxicity and a recent reanalysis of historical data casts doubt on its clinical efficacy and potential for toxicity. Despite treatment, 12% of patients hospitalised for LF die. Overall, the absence of state-of-the-art intensive care, the questionable effectiveness and important toxicity of ribavirin, its high cost and the significant burden of LF in West Africa call for novel drug therapies.
The INTEGRATE consortium builds on a more than 15 years lasting highly successful collaboration between leading European and West African research and health care institutions focusing on the joint priority to better understand, manage, and combat LF in West Africa.
In this context, the general objective of the INTEGRATE project is to establish a platform clinical trial in West Africa to assess the efficacy, safety, tolerability and pharmacokinetics of repurposed and novel drug candidates for the treatment of LF. To address this overall objective, the project will target 3 specific objectives (SO):
- Objective 1: to develop and implement an adaptive randomised controlled phase II-III clinical platform trial in West Africa evaluating repurposed and novel antiviral drugs with proven preclinical activity against LF.
- Objective 2: to build capacity for sustainable and independently conducted clinical research in West Africa.
- Objective 3: to engage communities with the proposed work plan and to assess acceptability of the trial.
INTEGRATE brings together social science researchers, Lassa fever medical experts, operational experts, and community-based partners to work with local communities to promote support for and participation in the clinical trial. Getting people with LF to participate in the INTEGRATE clinical trial is essential for its success. However, several barriers can limit participation and addressing these challenges is critical. However, to date, no studies have explored these issues in the context of Lassa fever trials in Nigeria. The use of exploratory qualitative research, plays a crucial role in ensuring the success of the INTEGRATE project by addressing sociocultural and psychological factors affecting participation.
Transmitted from contact with certain rats or from person to person through infected body fluids, LF virus acts with devastating speed, killing people within 10 days of their first symptoms if not correctly treated.
The current standard of care for LF is ribavirin but is associated with important toxicity and a recent reanalysis of historical data casts doubt on its clinical efficacy and potential for toxicity. Despite treatment, 12% of patients hospitalised for LF die. Overall, the absence of state-of-the-art intensive care, the questionable effectiveness and important toxicity of ribavirin, its high cost and the significant burden of LF in West Africa call for novel drug therapies.
The INTEGRATE consortium builds on a more than 15 years lasting highly successful collaboration between leading European and West African research and health care institutions focusing on the joint priority to better understand, manage, and combat LF in West Africa.
In this context, the general objective of the INTEGRATE project is to establish a platform clinical trial in West Africa to assess the efficacy, safety, tolerability and pharmacokinetics of repurposed and novel drug candidates for the treatment of LF. To address this overall objective, the project will target 3 specific objectives (SO):
- Objective 1: to develop and implement an adaptive randomised controlled phase II-III clinical platform trial in West Africa evaluating repurposed and novel antiviral drugs with proven preclinical activity against LF.
- Objective 2: to build capacity for sustainable and independently conducted clinical research in West Africa.
- Objective 3: to engage communities with the proposed work plan and to assess acceptability of the trial.
INTEGRATE brings together social science researchers, Lassa fever medical experts, operational experts, and community-based partners to work with local communities to promote support for and participation in the clinical trial. Getting people with LF to participate in the INTEGRATE clinical trial is essential for its success. However, several barriers can limit participation and addressing these challenges is critical. However, to date, no studies have explored these issues in the context of Lassa fever trials in Nigeria. The use of exploratory qualitative research, plays a crucial role in ensuring the success of the INTEGRATE project by addressing sociocultural and psychological factors affecting participation.
The project was launched on July 1st 2023. The online kick off meeting gathered all consortium members on July 25th 2023. In November 2023, consortium members gathered in Ivory Coast, for a face-to-face 3-days workshop, aiming to progress in the protocol writing addressing major scientific issues, to make progress within WP, reviewing coming deliverables and to discuss subsequent steps.
Sponsors met in Paris during the Eleventh EDCTP forum in November 2023 and a first training in pharmacovigilance was provided, from the co-sponsor (ANRS-MIE) to the sponsor (ISTH) as part of the capacity building program. A second meeting was held in Lagos, Nigeria in June 2024 to clearly define the allocation of sponsor responsibilities in a Sponsorship Agreement.
During this period, the project was dedicated on the initiation of all activities and trial preparation. Activities were mainly focused on the i) legal and contractual settings initiation and finalization, ii) study documents writing, iii) FMCO and ISTH sites preparation, iv) obtaining ethical and regulatory approval, and v) plan the site initiation visit for sites activation. The Scientific Advisory Board and the IMP board were requested in order to adress them all scientific issues arising from the protocol drafting and to receive any recommendations.
The INTEGRATE trial protocol v1.0 was submitted to national competent in January 2024. All approvals were obtained by November 2024. Amendments were made, and the protocol v2.0 is currently under review by the regulatory authority.
Study agreements were drafting and are currently under review by all partners.
The building of laboratory capacities at study sites has been successfully handled. The technology and knowledge transfer were provided continuously, increasing substantial improvement of patient care and the setup of laboratory capacities. Preparation of laboratories was done during this 18-month period and the laboratory infrastructures were set up in both sites in January 2025. ISTH and FMCO laboratories are now ready to receive samples from the trial.
The research formative study was conducted from January to July 2024, in Nigeria, in both Ondo and Edo States. The report was provided in July 2024 and a sensitization strategy was defined in November 2024 and is currently being implemented in Nigeria.
The institutional capacity building plan providing a training schedule of all sites taking part in INTEGRATE was developed, agreed and delivered in December 2023. Representatives of the sites ISTH and FMCO were trained on clinical research in a two-weeks hands-on course in October 2024 in Gabon. ISTH and FMCO team also received the clinical trial training on the protocol and all study documents in January-February 2025. The INTEGRATE project webpage was put online in December 2023. A press release on INTEGRATE was disseminated by to international media during the Lassa fever peak season in March 2024, resulting in press and radio opportunities.
Sponsors met in Paris during the Eleventh EDCTP forum in November 2023 and a first training in pharmacovigilance was provided, from the co-sponsor (ANRS-MIE) to the sponsor (ISTH) as part of the capacity building program. A second meeting was held in Lagos, Nigeria in June 2024 to clearly define the allocation of sponsor responsibilities in a Sponsorship Agreement.
During this period, the project was dedicated on the initiation of all activities and trial preparation. Activities were mainly focused on the i) legal and contractual settings initiation and finalization, ii) study documents writing, iii) FMCO and ISTH sites preparation, iv) obtaining ethical and regulatory approval, and v) plan the site initiation visit for sites activation. The Scientific Advisory Board and the IMP board were requested in order to adress them all scientific issues arising from the protocol drafting and to receive any recommendations.
The INTEGRATE trial protocol v1.0 was submitted to national competent in January 2024. All approvals were obtained by November 2024. Amendments were made, and the protocol v2.0 is currently under review by the regulatory authority.
Study agreements were drafting and are currently under review by all partners.
The building of laboratory capacities at study sites has been successfully handled. The technology and knowledge transfer were provided continuously, increasing substantial improvement of patient care and the setup of laboratory capacities. Preparation of laboratories was done during this 18-month period and the laboratory infrastructures were set up in both sites in January 2025. ISTH and FMCO laboratories are now ready to receive samples from the trial.
The research formative study was conducted from January to July 2024, in Nigeria, in both Ondo and Edo States. The report was provided in July 2024 and a sensitization strategy was defined in November 2024 and is currently being implemented in Nigeria.
The institutional capacity building plan providing a training schedule of all sites taking part in INTEGRATE was developed, agreed and delivered in December 2023. Representatives of the sites ISTH and FMCO were trained on clinical research in a two-weeks hands-on course in October 2024 in Gabon. ISTH and FMCO team also received the clinical trial training on the protocol and all study documents in January-February 2025. The INTEGRATE project webpage was put online in December 2023. A press release on INTEGRATE was disseminated by to international media during the Lassa fever peak season in March 2024, resulting in press and radio opportunities.
As planned per project proposal, we have designed a protocol v2.0. We currently start this platform in Nigeria, and will expend it to Liberia, Guinea and Benin as soon as these Sites will be ready to enter the trial.
The consortium is committed to strengthening structures to improve quality of care and laboratory facilities as well as the initiation, planning, implementation, coordination and oversight clinical trials by the African partner institutions. Major focus for the initial period was the completion of strengthening laboratory capacities and individual skills. State-of-the-art laboratories have been successfully established at two key sites in Nigeria, empowering these centers to deliver exceptional standards of care and produce robust, high-quality data. Individual knowledge transfer was successfully achieved by the formation of a broad council of clinical experts (physicians and nurses) from the participating sites and with a dedicated hands-on training on clinical trial conduct and management provided in Gabon. These achievements contribute to promote sustainable local ownership of research in West Africa.
Finally, the formative study was completed and informed the design and implementation of the Community sensitization strategy, which is aimed at promoting acceptability to participate in the clinical trial in Nigeria. Results will provide new knowledge on the perspectives of community members and leaders on the acceptability of participating in a clinical trial on Lassa fever in Ondo and Edo States, Nigeria.
The consortium is committed to strengthening structures to improve quality of care and laboratory facilities as well as the initiation, planning, implementation, coordination and oversight clinical trials by the African partner institutions. Major focus for the initial period was the completion of strengthening laboratory capacities and individual skills. State-of-the-art laboratories have been successfully established at two key sites in Nigeria, empowering these centers to deliver exceptional standards of care and produce robust, high-quality data. Individual knowledge transfer was successfully achieved by the formation of a broad council of clinical experts (physicians and nurses) from the participating sites and with a dedicated hands-on training on clinical trial conduct and management provided in Gabon. These achievements contribute to promote sustainable local ownership of research in West Africa.
Finally, the formative study was completed and informed the design and implementation of the Community sensitization strategy, which is aimed at promoting acceptability to participate in the clinical trial in Nigeria. Results will provide new knowledge on the perspectives of community members and leaders on the acceptability of participating in a clinical trial on Lassa fever in Ondo and Edo States, Nigeria.