Africa and Europe have signed a partnership to launch the first ever Phase 3 of clinical trial in early pregnancy that will leverage clinical and social research to better serve women of reproductive age at risk of malaria.
According to a Kenya medical research Institute (KEMRI) press release, The Safety of Antimalarials in the FIrst TRimEster (SAFIRE) consortium, made up of scientific and social research experts in malaria in pregnancy, kicked off the preparation of a historic project: the first-ever Phase 3 clinical trial.The trial will evaluate the efficacy, safety, tolerability and cost-effectiveness of antimalarial drugs to treat uncomplicated malaria in pregnancy.
“We are thrilled to begin this first-of-its-kind trial. Pregnant women are typically excluded from clinical trials for fear of causing harm to the mother and the baby she is carrying. Determining which antimalarial medicines are efficacious and well tolerated in the first trimester will benefit all women of Childbearing age, including those who may be unaware that they are pregnant, by enabling them to take these medicines without risk of causing harm to themselves or their unborn babies,” said Dr Hellen Barsosio, one of the project’s scientific co-leads and a Research Scientist of maternal and newborn health at Kenya Medical Research Institute (KEMRI).
The Safety of Antimalarials in the First TRimEster (SAFIRE) consortium, which consists of social scientists and experts in malaria in pregnancy, will lead this important endeavour.
The launch of a phase 3 clinical trial will challenge the current paradigm, which generally excludes pregnant women from clinical studies, and fill a crucial gap by concentrating on a group that is frequently overlooked: women in their first trimester.
The project will be financed by the Swiss State Secretariat for Education, Research, and Innovation (SERI) and the Global Health EDCTP3 Joint Undertaking (EDCTP3), a collaboration supported by European and African nations as well as the European Union. Through social research and an adaptive platform trial, SAFIRE will produce strong data about the safety, effectiveness, and tolerability of antimalarials during the first trimester of pregnancy.
The project’s outcomes will inform policies and standards, enabling women to receive the best possible care during their early pregnancies.
“The enrolment of women in the trial will start in 2025 pending data from the MiMBa pregnancy registry and PYRAPREG studies,”
The majority of pregnant women face serious health risks related to malaria, including low birthweight, preterm delivery, miscarriage, stillbirth, severe maternal anemia, severe malaria, and maternal mortality. Additionally, there are limited therapeutic options available for first-trimester pregnant women.
The World Health Organization recommends artemisinin-based combination treatments (ACTs) as the first line of treatment for malaria. However, as of 2022, only one ACT—artemether-lumefantrine (AL)—is indicated for use in the treatment of uncomplicated malaria in the first trimester.
In an attempt to thwart mitigation, diversifying the ACTs used to treat malaria may unintentionally expose first-trimester pregnant women to medications other than AL. The trial will first assess two treatment arms: Pyronaridine-artesunate (PA) with the commonly used AL acting as the comparison, in an effort to proactively address potential hazards.
The Amsterdam University Medical Center leads SAFIRE research on shielding expectant mothers from antimalarial medications, with scientific co-leadership from KEMRI and the University of Sciences, Techniques and Technologies of Bamako (USTTB). Medicines for Malaria Venture (MMV) and the Liverpool School of Tropical Medicine (LSTM), which will contribute scientific and technical expertise, are co-sponsors of the Phase 3 clinical trial.
An important step forward for global health research, this initiative will be the first Bayesian adaptive platform trial evaluating the safety, effectiveness, and tolerability of antimalarial medicines in the first trimester of pregnancy.
Future studies targeting other infectious diseases that primarily impact pregnant women in low- and middle-income countries will be designed with the assistance of the data acquired by SAFIRE from research that will commence in Burkina Faso, Kenya, and Mali.
In order to inform the final trial design and develop culturally acceptable methods for participant identification, recruitment, and retention throughout the trial, social and implementation research will give representatives from participating institutions the opportunity to lead formative research as a first step.
“Engaging with the community to build trust, and understand possible recruitment barriers like cultural sensitivities as well as women’s concerns about taking medicines in early pregnancy, will be crucial for an ethical and successful enrolment of women in the clinical study,” said Maud Majeres Lugand, Associate Director of Social Research at MMV.
The WHO’s Global Technical Strategy for Malaria and the UN Sustainable Development Goals for Health both state that the world health community is falling short of its 2030 deadline for ending malaria.
“It took 20 years for WHO to recommend AL to treat malaria in the first trimester. There is an urgent need to provide alternative therapeutic options in this very sensitive phase of pregnancy,” said Prof. Kassoum Kayentao of USTTB, and scientific co-lead of SAFIRE.
Encouraging the acceleration of progress towards the elimination of malaria is the aim of SAFIRE. The study’s data will be shared to help healthcare professionals create policies and carry them out locally.
“The trial will provide an evidence base to make an additional ACT available for malaria treatment in the first trimester, and also contribute to addressing the lack of equity in enrolling pregnant women in clinical trials”, said Prof. Kayentao.
