ANTICOV: largest clinical trial in Africa for people with mild COVID-19 to test new drug combination
The ANTICOV clinical trial, conducted in 13 African countries, has started the recruitment of participants to test a new drug combination, nitazoxanide + ciclesonide, to treat people with mild-to-moderate COVID-19 before their cases become severe.
The ANTICOV study is being carried out by a consortium of 26 partners which include leading African research institutions and international health organizations, coordinated by the non-profit research and development (R&D) organization Drugs for Neglected Diseases initiative (DNDi). It is the largest trial in Africa to identify early COVID-19 treatments that can prevent progression to severe disease and potentially limit transmission.
“In many African countries our worst fears are being realised, as already-strained intensive care units are beginning to fill up with COVID-19 patients,” said Dr John Nkengasong, Director of the Africa Centres for Disease Control and Prevention (Africa CDC). “Yet the number of vaccine doses that are reaching the African continent is too limited. The rapid spread of new variants also threatens to reduce the efficacy of existing vaccines, which is another major cause for concern. We need urgently to identify affordable and easy-to-administer treatments that can prevent the evolution to a severe form of the disease and slow the rate of infection.”
The Africa CDC has recorded more than 117,000 deaths from COVID-19 on the continent; however, the true toll is estimated to be higher. And with new variants spreading, an increase in new cases is expected in the coming months.
ANTICOV is testing a new potential treatment that combines the well-known antiparasitic nitazoxanide and the inhaled corticosteroid ciclesonide. The combination has two different mechanisms of action that could work at different stages of infection: one that is potentially active during the first, viral replication stage of SARS-COV-2 infection and one that decreases the likelihood of an inflammatory stage that can start a few days later. Both drugs are already commercially available and will be affordable and easy to access and administer, if shown to be effective against COVID-19.
“It has been more than a year since COVID-19 was declared a pandemic, and while we have vaccines registered for use, there are still very few treatment options – especially for the early stage when we could prevent severe progression, potentially reduce transmission, and maybe prevent the risk of developing post-COVID condition,” said Dr Nathalie Strub-Wourgaft, Director of the COVID-19 Response for DNDi. “We still do not have a treatment for mild-to-moderate cases and this remains a research priority, in Africa – and throughout the world.”
The inclusion of the nitazoxanide + ciclesonide combination in a new arm of the ANTICOV study has been reviewed through the WHO-created African Vaccine Regulatory Forum (AVAREF) – which facilitated the regulatory process in each ANTICOV country – and by the WHO COVID-19 Research Ethics Review Committee.
“In addition to treatment options for patients with mild-to-moderate COVID-19, we also need a simple, easy-to-use, affordable, and reliable test that can be the backbone of test-and-treat programmes led by African governments,” said Dr Monique Wasunna, Director of the DNDi Africa regional office. “We fully support the work of our ANTICOV Consortium partner The Foundation For Innovative New Diagnostics (FIND), which is a co-convener of the ACT Accelerator Diagnostics Partnership, to accelerate diagnostic tools for COVID-19.”
The first participants in the new study arm have been recruited in the Democratic Republic of Congo (DRC) and the Republic of Guinea. In the coming weeks, additional trial sites will enrol participants in Burkina Faso, Cameroon, Côte d’Ivoire, Equatorial Guinea, Ethiopia, Ghana, Kenya, Mali, Mozambique, Sudan, and Uganda.
“As we face a mutating virus that challenges the tools we have to fight COVID-19, research into promising treatments has never been more important. It is vital to work out which therapeutics we can add to the existing package of patient care - and how they can be best-adapted for use in low-resource settings,” said Dr Philippe Duneton, Executive Director of Unitaid, which is partly funding the study. “Through the ANTICOV trial, Unitaid is investing in potential drugs to treat mild and moderate COVID-19 - a key gap in current treatment options that we must bridge to prevent hospitalisations and deaths.”
ANTICOV is an ‘adaptive platform’ trial, a flexible and innovative trial design that allows for treatments to be added or removed as new evidence emerges. The trial started in September 2020 with the HIV antiretroviral combination lopinavir/ritonavir and the malaria drug hydroxychloroquine. These two initial arms were suspended in December 2020 after WHO updated its treatment guidelines to recommend against the use of these drugs to treat COVID-19 patients, including patients with mild-to-moderate COVID-19.
The ANTICOV Consortium is now in the process of selecting and preparing the next arm of the trial. The selection of trial drugs for ANTICOV is informed by reviews conducted by the expert working group of the Unitaid and Wellcome-led Access to COVID-19 Tools Accelerator (ACT-A) Therapeutics Partnership.
Major funding for the ANTICOV consortium is provided by the German Federal Ministry of Education and Research (BMBF) through KfW and by the global health agency Unitaid as part of ACT-A. Additional support comes from the European & Developing Countries Clinical Trials Partnership (EDCTP) - under its second programme supported by the European Union with additional funding from the Swedish government -, the Starr International Foundation and the Stavros Niarchos Foundation (SNF).
A not-for-profit research and development organization, DNDi works to deliver new treatments for neglected patients, those living with Chagas disease, sleeping sickness (human African trypanosomiasis), leishmaniasis, filarial infections, mycetoma, paediatric HIV, and hepatitis C. DNDi is also coordinating the ANTICOV clinical trial to find treatments for mild-to-moderate COVID-19 cases in Africa. Since its inception in 2003, DNDi has delivered eight new treatments to date, including new drug combinations for kala-azar, two fixed-dose antimalarials, and DNDi’s first successfully developed new chemical entity, fexinidazole, approved in 2018 for the treatment of both stages of sleeping sickness.
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