[Português]

The ANTICOV study, a platform clinical trial which aims to find early treatments for mild-to-moderate cases of COVID-19 and is currently conducted in 13 African countries, is expanding to Brazil through a collaboration with the TOGETHER study team, a Brazilian-Canadian partnership that is running another large platform trial in the country.  

‘The COVID-19 pandemic is far from over. New waves fuelled by new variants are still putting public health systems around the world under heavy strain,’ said Dr Nathalie Strub-Wourgaft, Director of the COVID-19 Response for the non-profit research and development organization Drugs for Neglected Diseases initiative (DNDi), which is coordinating the ANTICOV consortium.  

‘We still need oral COVID-19 treatments that are safe, affordable, and globally accessible. We need easy-to-administer drugs for outpatients diagnosed within seven days after the first appearance of symptoms. The TOGETHER study has already identified two effective treatments for patients with mild-to-moderate symptoms, and we welcome this partnership with its researchers in Brazil.’  

Launched in September 2020, ANTICOV is a collaboration of now 27 partners from leading research institutions and international health organizations aiming to identify COVID-19 treatments that are optimized for use in low- and middle-income countries (LMICs) and that can prevent progression to severe disease.  

The ANTICOV trial in Brazil will include up to 600 patients in up to 21 sites. The data gathered will be pooled with the existing ANTICOV study carried out in 13 African countries. 

‘The goal of ANTICOV is to identify the best treatment regimen that could be used for test-and-treat strategies in LMICs – and could therefore prevent the evolution to a severe form, potentially limit transmission, reduce the risk of developing a long-COVID, and prevent hospitalization and death that periodically threaten to overwhelm hospitals,’ said Dr Gilmar Reis, Associate Professor at the Universidade Catolica de Minais Gerais and Co-Principal Investigator of the TOGETHER trial. ‘This is a research priority and the expansion of the ANTICOV trial to Brazil is bringing us closer to that goal.’ 

More than 6,000 patients have enrolled to date in the TOGETHER trial, which has evaluated 11 treatments for patients with mild-to-moderate COVID-19 cases. The TOGETHER trial has already shown in August 2021 that a compound named fluvoxamine is effective against COVID-19 and can reduce deaths and hospitalizations by up to 30%. More recently in March 2022, the trial has also found that peginterferon lambda reduced hospitalizations or death by 60% with early treatment. 

The ANTICOV trial in Brazil will start by testing a new drug combination, fluoxetine and inhaled budesonide. Fluoxetine is a safe and widely available anti-depressant that belongs to the same class of compounds as fluvoxamine. Budesonide is a safe and affordable inhaled corticosteroid thought to have anti-inflammatory efficacy against COVID-19. Studies have shown that budesonide, if taken early enough, improves recovery time in outpatients with COVID-19 and may reduce hospitalizations and deaths. The combination could be effective for the first, viral replication stage of the infection and could also decrease the impact of the later, inflammatory stage that can start a few days later.  

This is the fifth arm tested by ANTICOV. 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. Data from the ANTICOV trial has already demonstrated that the drug combination nitazoxanide and ciclesonide has low probability of reducing the risk of hospitalization in COVID-19 outpatients in comparison with paracetamol. 

The selection of drugs for ANTICOV is informed by reviews conducted by the expert working group of the Unitaid, Wellcome, and Global Fund-led Access to COVID-19 Tools Accelerator (ACT-A) Therapeutics Partnership. The study will soon expand to South Asia.  

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).

List of ANTICOV partners 

The ANTICOV consortium is mobilizing a wide network of diverse partners with recognised experience in clinical research. The 27 members of the ANTICOV consortium are: 

• ALIMA (The Alliance for International Medical Action), France / Senegal 
• ANRS | Maladies infectieuses émergentes, France 
• Bahir Dar University, Ethiopia 
• Barcelona Institute for Global Health (ISGlobal), Spain 
• Bernhard-Nocht-Institut für Tropenmedizin (BNITM), Germany 
• Centre Muraz, Institut National de Santé Publique, Burkina Faso 
• Centre for Research in Therapeutic Sciences, Kenya 
• Centro de Investigação em Saúde de Manhiça, Mozambique 
• Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC), Instituto Nacional de Saúde, Mozambique 
• Centre Pasteur du Cameroun (CPC), Cameroon 
• Centre Pour Le Développement Des Vaccins, Ministry of Health, Mali 
• Centre Suisse de Recherches Scientifiques (CSRS), Côte d’Ivoire 
• Drugs for Neglected Diseases initiative (DNDi), Switzerland (coordinating partner) 
• Epicentre, France 
• FIND, the global alliance for diagnostics, Switzerland 
• Ifakara Health Institute, Tanzania 
• Infectious Diseases Data Observatory (IDDO), United Kingdom 
• Institute of Endemic Diseases, University of Khartoum, Sudan 
• Institute of Tropical Medicine, Antwerp (ITM), Belgium 
• Institut National de Recherche Biomédicale (INRB), Democratic Republic of Congo 
• The Kenya Medical Research Institute (KEMRI), Kenya 
• Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Ghana 
• Medicines for Malaria Venture (MMV), Switzerland 
• Swiss Tropical and Public Health Institute (Swiss TPH), Switzerland 
• TOGETHER trial, Brazil, Canada 
• Université de Bordeaux – Institut National de la Santé et de la Recherche Médicale (INSERM), France 
• University of Gondar, Ethiopia 

ANTICOV’s innovative and flexible platform trial has been designed by Berry Consultants, LLC, a statistical consulting company specializing in the Bayesian approach to medical statistics. 

Media contacts 

DNDi 

Frédéric Ojardias (Geneva) 
fojardias@dndi.org  
+41 79 431 62 16  

Marcela Dobarro (Rio) 
mdobarro@dndi.org  
+55 21 25 29 04 14 

Ilan Moss (New York) 
imoss@dndi.org 
+1 646 266 5216 

TOGETHER 

Dr Edward Mills (Vancouver) 
Co-Principal Investigator, TOGETHER Trial 
emills@platformlifescineces.com  
+1 604 731 0688 

About DNDi

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 low-resource settings. Since its inception in 2003, DNDi has delivered twelve 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.  dndi.org

About TOGETHER 

The TOGETHER Trial represents an international collaboration of diverse partners committed to preventing death and improving health outcomes for all people affected by COVID-19. Resources and expertise from all countries working in TOGETHER network are being brought to bear to identify new potential uses of new existing medications, which can be used to prevent COVID-19 related morbidity and mortality. This international trial is financially supported by a mix of biotechnology companies and private sector philanthropic agencies, which have dedicated financial resources to the fight against COVID-19 in low and middle-income countries. www.togethertrial.com  

Photo credit: CardResearch, Belo Horizonte, Minas Gerais, Brazil

The post Brazil joins ANTICOV trial to find early treatments for people with mild-to-moderate COVID-19 appeared first on ANTICOV Trial.

[Deutsch] [Français]

The Drugs for Neglected Diseases initiative (DNDi), on behalf of a consortium of 26 African and global research organizations, expressed concern today that efforts to conduct urgently needed studies in low- and middle-income countries (LMICs) utilizing the novel oral antiviral, nirmatrelvir/ritonavir (Paxlovid), are being blocked by Pfizer, which developed the drug.

Nirmatrelvir/ritonavir has emerged as one of the most promising antiviral treatments for outpatients with mild-to-moderate COVID-19, reducing the risk of hospitalization or death by up to 89% in patients at high risk of severe disease.^[1] This and other novel oral antiviral treatments will be a critical part of the therapeutic arsenal to treat patients today and prepare for future waves. However, the treatment must be taken within 3-5 days of symptom onset to be effective and reaching patients this early in the course of their infection is challenging.

But an interim analysis done in the context of the ongoing ANTICOV clinical trial conducted in 10 African countries showed that of the 1180 patients enrolled, more than half present for care after day 5 (mean 5.1 days, median 5.0 days). This means that even in a clinical trial setting, more than half of patients would not benefit from nirmatrelvir/ritonavir.

To overcome this challenge, it is necessary to explore whether using nirmatrelvir/ritonavir with other drugs could widen the ‘treatment window’ to at least 7 days and be beneficial for immune-suppressed patients who are the most vulnerable to disease progression but were excluded from phase 3 trials (as such, there is no robust evidence available to guide the therapeutic strategies).

DNDi and academic investigators from large university hospitals in Europe have separately approached Pfizer about potential collaborations on combination studies in LMICs but Pfizer has declined to provide access to the drug for research purposes.

‘There are critically important public health research questions that must be answered quickly – particularly in low- and middle-income countries where access to vaccines remains low,’ said Dr Nathalie Strub-Wourgaft, Director of DNDi’s COVID-19 Response and one of the coordinators of the ANTICOV Consortium. ‘It is difficult to understand any rationale for refusing to cooperate in the midst of a global pandemic, and this sets a dangerous precedent since there are many other promising antivirals in the pipeline and these novel treatments will also require follow-on research to determine their optimal use in resource-limited settings.’

DNDi is also concerned about additional hurdles in obtaining generic versions of the drug to conduct the relevant combination studies via ANTICOV. For example:

• The terms of the Pfizer/Medicines Patent Pool (MPP) licensing agreement  could be interpreted to mean that sub-licensees cannot provide nirmatrelvir/ritonavir for use in the sorts of combination studies that DNDi and others wish to conduct, unless they have explicit written approval from Pfizer.^[2]
• Some generic manufacturers are also encountering difficulties obtaining Paxlovid as a ‘reference drug’ so that they can conduct the necessary bioequivalence studies to show regulators that their generic version has the same effect in the body, effectively blocking availability of generics for both research and clinical use.

‘Every effort should be made to ensure that clinical studies for COVID-19 treatment are conducted in low- and middle-income countries, and that any products developed reach vulnerable populations,’ said Dr John Amuasi, Leader, Global Health and Infectious Diseases Research Group, Kumasi Center for Collaborative Research in Tropical Medicine in Ghana and a principal investigator for ANTICOV. ‘We must not arrive at a situation where research priorities are determined by the actions or inactions of any company.’

DNDi, the ANTICOV Consortium, and other clinical researchers therefore ask Pfizer to:

1. Agree to provide access to nirmatrelvir/ritonavir (Paxlovid) for the DNDi-coordinated ANTICOV trial and other relevant clinical trials;
2. Remove any ambiguities or restrictions in the Pfizer-MPP licensing agreement that could prevent sub-licensees from  supplying such research studies (or publicly clarify that no such restrictions exist);
3. Provide access to Pfizer’s originator product as a ‘reference drug’ so that any interested generic manufacturer can conduct the necessary bioequivalence studies for regulatory approval; and
4. Allocate sufficient quantities of Paxlovid specifically for LMICs and remove all barriers to access to generic nirmatrelvir/ritonavir to enable scale up for care and treatment in LMICs.

About DNDi

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 low- and middle-income countries. Since its inception in 2003, DNDi has delivered nine 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. dndi.org

Media contacts

Frédéric Ojardias (Geneva)
fojardias@dndi.org 
+41 79 431 62 16 

Ilan Moss (New York)
imoss@dndi.org
+1 646 266 5216

^[1] See FDA News Release, December 22, 2021: Coronavirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19 | FDA

^[2] Pfizer-MPP License and Sublicense (Execution Version), November 2021.

The post Pfizer blocking research to generate evidence on optimal use of novel antiviral for COVID-19 patients in low- and middle-income countries appeared first on ANTICOV Trial.

[Français] [Português]

The ANTICOV platform clinical trial, launched in September 2020 in 13 African countries to identify treatments for mild and moderate cases of COVID-19, has stopped recruiting patients into one of its treatment arms, the drug combination nitazoxanide and inhaled ciclesonide.

ANTICOV is testing several treatment combinations, and pre-planned interim analyses are regularly conducted to assess if any of the tested arms could be stopped before the trial ends, if they show signals of very high – or lack of – efficacy. Following its third interim efficacy analysis performed on a total of 946 patients enrolled in all arms with a known last visit (day 21) outcome, the ANTICOV independent Data and Safety Monitoring Board (DSMB) concluded that early futility (meaning very low efficacy) has been demonstrated for the nitazoxanide/inhaled ciclesonide arm of the trial.

Interim efficacy analyses showed that 1.13% of patients (5 of 443) in the control arm (paracetamol) saw their symptoms deteriorate (their blood oxygen level decreased below the 93% threshold) compared to 3.25% of patients (15 of 462) treated with the nitazoxanide/ciclesonide combination. The DSMB therefore concluded that there has been no convincing evidence of the efficacy of this combination on COVID-19 patients with mild to moderate symptoms, compared to the control arm. These results show that nitazoxanide/ciclesonide combination treatment has very little chance of preventing progression to severe symptoms of COVID-19 compared to the control arm.

The DSMB also concluded that no safety issues were detected.

The ANTICOV Joint Steering Committee endorsed the recommendation from the DSMB to stop recruitment in this arm.

‘We need large, context-specific treatment trials for low- and middle-income countries that have largely been left out of COVID-19 research, to guide us on what works and what does not,’ said Dr Nathalie Strub-Wourgaft, head of the COVID-19 response at the Drugs for Neglected Diseases initiative (DNDi), which is coordinating the trial. ‘This result achieved by the hard work of investigators in ANTICOV partner countries illustrates the value of platform trials. This is important evidence that was generated in Africa, by African researchers with their international partners, and that will inform decisions both in Africa and globally.‘

The ANTICOV trial is an open-label, randomized, comparative, adaptive platform trial that aims to identify COVID-19 treatments that are optimized for use in resource-limited settings and that can prevent progression to severe disease and potentially limit transmission. ANTICOV’s flexible and innovative trial design allows for treatments to be added or removed as evidence emerges.

ANTICOV will continue to recruit patients into its other treatments arms, including the recently announced combination drugs fluoxetine and budesonide.

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).

List of ANTICOV partners 

The ANTICOV consortium is mobilizing a wide network of diverse partners with recognised experience in clinical research. The 26 members of the ANTICOV consortium are: 

• ALIMA (The Alliance for International Medical Action), France / Senegal 
• ANRS | Maladies infectieuses émergentes, France 
• Bahir Dar University, Ethiopia 
• Barcelona Institute for Global Health (ISGlobal), Spain 
• Bernhard-Nocht-Institut für Tropenmedizin (BNITM), Germany 
• Centre Muraz, Institut National de Santé Publique, Burkina Faso 
• Centre for Research in Therapeutic Sciences, Kenya 
• Centro de Investigação em Saúde de Manhiça, Mozambique 
• Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC), Instituto Nacional de Saúde, Mozambique 
• Centre Pasteur du Cameroun (CPC), Cameroon 
• Centre Pour Le Développement Des Vaccins, Ministry of Health, Mali 
• Centre Suisse de Recherches Scientifiques (CSRS), Côte d’Ivoire 
• Drugs for Neglected Diseases initiative (DNDi), Switzerland (coordinating partner) 
• Epicentre, France 
• FIND, the global alliance for diagnostics, Switzerland 
• Ifakara Health Institute, Tanzania 
• Infectious Diseases Data Observatory (IDDO), United Kingdom 
• Institute of Endemic Diseases, University of Khartoum, Sudan 
• Institute of Tropical Medicine, Antwerp (ITM), Belgium 
• Institut National de Recherche Biomédicale (INRB), Democratic Republic of Congo 
• The Kenya Medical Research Institute (KEMRI), Kenya 
• Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Ghana 
• Medicines for Malaria Venture (MMV), Switzerland 
• Swiss Tropical and Public Health Institute (Swiss TPH), Switzerland 
• Université de Bordeaux – Institut National de la Santé et de la Recherche Médicale (INSERM), France 
• University of Gondar, Ethiopia 

Media contacts 

Frédéric Ojardias (Geneva) 
fojardias@dndi.org  
+41 79 431 62 16 

Francine Ngalula (Kinshasa) 
francinengal@gmail.com  
+243 816 402 389 

Linet Atieno Otieno (Nairobi) 
latieno@dndi.org  
+254 705 63 99 09 

Ilan Moss (New York) 
imoss@dndi.org 

+1 646 266 5216 

About DNDi

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 nine 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. dndi.org

The post ANTICOV trial finds drug combination nitazoxanide + ciclesonide does not reduce risk of hospitalization in COVID-19 outpatients  appeared first on ANTICOV Trial.

[Français]

The ANTICOV platform clinical trial has started the recruitment of participants to test a new promising drug combination, fluoxetine and budesonide, as an early treatment for people affected with mild-to-moderate COVID-19.

The ANTICOV trial, currently conducted in 13 African countries and soon expanding to additional countries in South Asia and Latin America, aims to identify COVID-19 treatments that are optimized for use in resource-limited settings and can prevent progression to severe disease and potentially limit transmission.

‘We urgently need to identify an oral COVID-19 treatment that is safe, affordable, accessible and adapted to the specific needs of low- and middle-income countries (LMICs)’ said Nathalie Strub-Wourgaft, Director of the COVID-19 Response for the non-profit research and development (R&D) organization the Drugs for Neglected Diseases initiative (DNDi), which coordinates the ANTICOV consortium.

‘COVID-19 antivirals recently approved for use in the United States, the European Union, India, and other countries show some promise on preventing disease progression when administered to high-risk patients in the first five days of symptoms. Concerns are growing whether these antivirals will be immediately available to everyone who needs them, especially in regions where access to vaccines remains unacceptably low. In low-income countries, less than 6% of people have been fully vaccinated against COVID-19,’ Dr Strub-Wourgaft said.

The new drug combination tested by ANTICOV includes fluoxetine, better known under its brand name Prozac. Fluoxetine’s potential for COVID is based on a mechanism of action that is totally separated from its anti-depressant properties: it inhibits the ability of the virus to replicate by preventing viral entry into cells and could also carry immunosuppressive activity. It is safe and widely available. Another molecule belonging to the same class of compounds was shown in August by the TOGETHER study to be effective against COVID-19, reducing deaths and hospitalizations by up to 30%.

Fluoxetine will be tested in combination with inhaled budesonide, a safe and affordable inhaled corticosteroid known to have potent anti-inflammatory efficacy in the lungs. Studies have shown that budesonide, if taken in an early stage of the infection, improves recovery time in outpatients with COVID and may reduce hospitalizations and deaths.

‘For outpatients presenting for treatment within a week of symptom onset, which corresponds to the reality on the ground, oral drugs combinations that are adding two different mechanisms of action – an antiviral and an anti-inflammatory – are the most promising options,’ said Dr Strub-Wourgaft. ‘Such a treatment will be particularly adapted to limited-resource settings where affordable testing tools are often difficult to access.’

The combination could be effective for the first, viral replication stage of the infection and could also decrease the likelihood of the second, inflammatory stage that can start a few days later.

Fluoxetine and budesonide are commercially available and will be affordable and easy to access and administer, if shown to be effective against COVID-19. This is the fifth arm tested by the ANTICOV trial since its launch in November 2020.

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 selection of 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).

List of ANTICOV partners 

The ANTICOV consortium is mobilizing a wide network of diverse partners with recognised experience in clinical research. The 26 members of the ANTICOV consortium are: 

• ALIMA (The Alliance for International Medical Action), France / Senegal 
• ANRS | Maladies infectieuses émergentes, France 
• Bahir Dar University, Ethiopia 
• Barcelona Institute for Global Health (ISGlobal), Spain 
• Bernhard-Nocht-Institut für Tropenmedizin (BNITM), Germany 
• Centre Muraz, Institut National de Santé Publique, Burkina Faso 
• Centre for Research in Therapeutic Sciences, Kenya 
• Centro de Investigação em Saúde de Manhiça, Mozambique 
• Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC), Instituto Nacional de Saúde, Mozambique 
• Centre Pasteur du Cameroun (CPC), Cameroon 
• Centre Pour Le Développement Des Vaccins, Ministry of Health, Mali 
• Centre Suisse de Recherches Scientifiques (CSRS), Côte d’Ivoire 
• Drugs for Neglected Diseases initiative (DNDi), Switzerland (coordinating partner) 
• Epicentre, France 
• FIND, the global alliance for diagnostics, Switzerland 
• Ifakara Health Institute, Tanzania 
• Infectious Diseases Data Observatory (IDDO), United Kingdom 
• Institute of Endemic Diseases, University of Khartoum, Sudan 
• Institute of Tropical Medicine, Antwerp (ITM), Belgium 
• Institut National de Recherche Biomédicale (INRB), Democratic Republic of Congo 
• The Kenya Medical Research Institute (KEMRI), Kenya 
• Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Ghana 
• Medicines for Malaria Venture (MMV), Switzerland 
• Swiss Tropical and Public Health Institute (Swiss TPH), Switzerland 
• Université de Bordeaux – Institut National de la Santé et de la Recherche Médicale (INSERM), France 
• University of Gondar, Ethiopia

Media contacts 

Frédéric Ojardias (Geneva) 
fojardias@dndi.org  
+41 79 431 62 16 

Francine Ngalula (Kinshasa) 
francinengal@gmail.com  
+243 816 402 389 

Linet Atieno Otieno (Nairobi) 
latieno@dndi.org  
+254 705 63 99 09 

Ilan Moss (New York) 
imoss@dndi.org 

+1 646 266 5216 

About DNDi

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 nine 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. dndi.org

Photo credit: Mountaga Drame / ALIMA

The post ANTICOV: clinical trial for COVID-19 in low-resource settings to test a new combination treatment, fluoxetine and budesonide appeared first on ANTICOV Trial.

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 120,000 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 conditions,’ 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 of COVID-19 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).

List of ANTICOV partners

The ANTICOV consortium is mobilizing a wide network of diverse partners with recognised experience in clinical research. The 26 members of the ANTICOV consortium are: 

• ALIMA (The Alliance for International Medical Action), France / Senegal
• Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS), France
• Bahir Dar University, Ethiopia
• Barcelona Institute for Global Health (ISGlobal), Spain
• Bernhard-Nocht-Institut für Tropenmedizin (BNITM), Germany
• Centre Muraz, Institut National de Santé Publique, Burkina Faso
• Centre for Research in Therapeutic Sciences, Kenya
• Centro de Investigação em Saúde de Manhiça, Mozambique
• Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC), Instituto Nacional de Saúde, Mozambique
• Centre Pasteur du Cameroun (CPC), Cameroon
• Centre Pour Le Développement Des Vaccins, Ministry of Health, Mali
• Centre Suisse de Recherches Scientifiques (CSRS), Côte d’Ivoire
• Drugs for Neglected Diseases initiative (DNDi), Switzerland – (coordinating partner)
• Epicentre, France
• Foundation for Innovative New Diagnostics (FIND), Switzerland
• Ifakara Health Institute, Tanzania
• Infectious Diseases Data Observatory (IDDO), United Kingdom
• Institute of Endemic Diseases, University of Khartoum, Sudan
• Institute of Tropical Medicine, Antwerp (ITM), Belgium
• Institut National de Recherche Biomédicale (INRB), Democratic Republic of Congo
• The Kenya Medical Research Institute (KEMRI), Kenya
• Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Ghana
• Medicines for Malaria Venture (MMV), Switzerland
• Swiss Tropical and Public Health Institute (Swiss TPH), Switzerland
• Université de Bordeaux – Institut National de la Santé et de la Recherche Médicale (INSERM), France
• University of Gondar, Ethiopia

About DNDi 

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. dndi.org

Media contacts

DNDi
Frédéric Ojardias (Geneva)
fojardias@dndi.org 
+41 79 431 62 16 

Danyell Odhiambo (Nairobi)
dodhiambo@dndi.org
+254 712 716 971

Ilan Moss (New York)
imoss@dndi.org
+1 646 266 5216

Francine Ngalula (Kinshasa)
francinengal@gmail.com
+243 816 402 389

Photo credit: Kenny Mbala-DNDi

The post ANTICOV: largest clinical trial in Africa for people with mild COVID-19 to test new drug combination appeared first on ANTICOV Trial.

Thirteen African countries and an international network of research institutions have joined forces to launch the largest COVID-19 clinical trial in mild-to-moderate outpatients in Africa. The ANTICOV clinical trial aims to respond to the urgent need to identify treatments that can be used to treat mild and moderate cases of COVID-19 early and prevent spikes in hospitalization that could overwhelm fragile and already overburdened health systems in Africa.

The clinical trial will be carried out at 19 sites in 13 countries by the ANTICOV consortium, which includes 26 prominent African and global research and development (R&D) organizations, coordinated by the Drugs for Neglected Diseases initiative (DNDi), an international non-profit drug research and development (R&D) group with extensive partnerships in Africa.

‘There is a need for large clinical trials in Africa for COVID-19 to answer research questions that are specific to an African context,’ said Dr John Nkengasong, Director of the Africa Centres for Disease Control and Prevention. ‘African countries have mounted an impressive response so far to COVID-19 and now is the time to prepare for future waves of the disease. We welcome the ANTICOV trial led by African doctors because it will help answer one of our most pressing questions: With limited intensive care facilities in Africa, can we treat people for COVID-19 earlier and stop our hospitals from being overwhelmed?’

ANTICOV is an open-label, randomised, comparative, ‘adaptive platform trial’ that will test the safety and efficacy of treatments in 2,000 to 3,000 mild-to-moderate COVID-19 patients in Burkina Faso, Cameroon, Côte d’Ivoire, the Democratic Republic of Congo (DRC), Equatorial Guinea, Ethiopia, Ghana, Guinea, Kenya, Mali, Mozambique, Sudan, and Uganda. ANTICOV aims to identify early treatments that can prevent progression of COVID-19 to severe disease and potentially limit transmission.

‘It is heartening to see so many African countries collaborate to get much-needed answers about our unique COVID-19 patient needs,’ said Dr Borna Nyaoke-Anoke, Senior Clinical Project Manager at DNDi, which is also the sponsor for clinical trials in the DRC, Kenya, and Sudan. ‘Africa has for the most part avoided the large-scale mortality seen in other countries, but with lockdowns ending and borders opening, we need to be prepared. We need research here in Africa that will inform policies and test-and-treat strategies, so that as clinicians we can give the best options to people with COVID-19.’

ANTICOV is an adaptive platform trial, an innovative type of clinical trial pioneered for cancer drugs that allows for several treatments to be simultaneously tested. Adaptive platform trials enable rapid decisions to be made, including adding, continuing, or stopping treatment arms based on an ongoing analysis of results.

New treatments will be added to the trial as evidence of their potential for mild-to-moderate cases emerges. ANTICOV researchers are actively looking to select the most promising treatments from ongoing global scientific efforts with proof of efficacy, in collaboration with the Access to COVID-19 Tools Accelerator (ACT-A) Therapeutics Partnership, co-convened by Unitaid and Wellcome on behalf of the COVID-19 Therapeutics Accelerator. Among the potential therapeutic options being explored by ANTICOV are medicines currently used to treat malaria, HIV, hepatitis C, parasitic infections, and certain cancers. The goal is to include additional treatment arms in the ANTICOV trial within weeks.

Initially, ANTICOV will focus on drugs where large-scale randomized clinical trials could provide missing efficacy data in mild-to-moderate patients. The trial will begin testing, against a control arm, the HIV antiretroviral combination lopinavir/ritonavir with a loaded dose and the malaria drug hydroxychloroquine, which remains the standard of care for COVID-19 today in numerous African countries.

‘The ANTICOV consortium is a broad partnership bringing African scientific leaders and global R&D organizations together to respond to an urgent unmet medical need. Collaboration is the only way to provide robust scientific responses to these research questions,’ said Dr Nathalie Strub-Wourgaft, Director of COVID-19 Response for DNDi. ‘The trial was designed in a way that enables rapid and flexible decisions as we gather knowledge.’

All clinical trial data generated by ANTICOV will be integrated and shared openly and transparently to inform public health policy. Every effort will be made to work with all relevant partners to ensure that treatments that prove safe and effective will be affordable, available, and accessible for all.   

The trial was reviewed with support from the African Vaccine Regulatory Forum (AVAREF), a platform established by the World Health Organization (WHO) in 2006, which was recently mandated to expedite clinical trial reviews for COVID-19. Made up of representatives from countries’ ethical and regulatory review bodies, AVAREF simplifies and helps accelerate country-level approvals.

ANTICOV is aligned with the WHO R&D Blueprint, which aims to improve coordination between scientists and global health professionals, accelerate the research and development process, and develop new norms and standards to learn from and improve upon the global COVID-19 response.

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. Early support to launch the initiative was provided by the European & Developing Countries Clinical Trials Partnership (EDCTP), under its second programme supported by the European Union with additional funding from the Swedish government, and the Starr International Foundation, Switzerland.

The ANTICOV consortium is mobilizing a wide network of diverse partners with recognised experience in clinical research. The 26 members of the ANTICOV consortium are:

• Alliance for International Medical Action (ALIMA), France / Senegal
• Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS), France
• Bahir Dar University, Ethiopia
• Barcelona Institute for Global Health (ISGlobal), Spain
• Bernhard-Nocht-Institut für Tropenmedizin (BNITM), Germany
• Centre Muraz, Institut National de Santé Publique, Burkina Faso
• Centre for Research in Therapeutic Sciences, Kenya
• Centro de Investigação em Saúde de Manhiça, Mozambique
• Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC), Instituto Nacional de Saúde, Mozambique
• Centre Pasteur du Cameroun (CPC), Cameroon
• Centre Pour Le Développement Des Vaccins, Ministry of Health, Mali
• Centre Suisse de Recherches Scientifiques (CSRS), Côte d’Ivoire
• Drugs for Neglected Diseases initiative (DNDi), Switzerland – (coordinating partner)
• Epicentre, France
• Foundation for Innovative New Diagnostics (FIND), Switzerland
• Ifakara Health Institute, Tanzania
• Infectious Diseases Data Observatory (IDDO), United Kingdom
• Institute of Endemic Diseases, University of Khartoum, Sudan
• Institute of Tropical Medicine, Antwerp (ITM), Belgium
• Institut National de Recherche Biomédicale (INRB), Democratic Republic of Congo
• The Kenya Medical Research Institute (KEMRI), Kenya
• Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Ghana
• Medicines for Malaria Venture (MMV), Switzerland
• Swiss Tropical and Public Health Institute (Swiss TPH), Switzerland
• Université de Bordeaux – Institut National de la Santé et de la Recherche Médicale (INSERM), France
• University of Gondar, Ethiopia

Media contacts

DNDi
Frédéric Ojardias (Geneva)
fojardias@dndi.org 
+41 79 431 62 16 

Linet Otieno (Nairobi)
latieno@dndi.org
+254 733 624 206

Ilan Moss (New York)
imoss@dndi.org
+1 646 266 5216

Francine Ngalula (Kinshasa)
francinengal@gmail.com
+243 816 402 389

Photo credit: Kenny Mbala-DNDi

The post Largest clinical trial in Africa to treat COVID-19 cases before they become severe is launched in 13 countries appeared first on ANTICOV Trial.