COVID-19 and clinical trials in adults – 6 questions for Kubéraka Mariampillai

Interview with Kubéraka Mariampillai, Project Manager for the Adult Clinical Trials platform at the Institute of Myology, headed by Prof. Bertrand Fontaine and coordinated by Dr Giorgia Querin, and member of “Inflammatory Myopathies and Innovative Targeted Therapies” team 8 at the Research Centre, headed by Prof. Olivier Benveniste.

If you could tell me who you are and what your missions are?
I am Kubéraka Mariampillai, Project Manager for the Adult Clinical Trials platform at the Institute of Myology, headed by Prof. Bertrand Fontaine and coordinated by Dr Giorgia Querin, and member of “Inflammatory Myopathies and Innovative Targeted Therapies” team 8, headed by Prof. Olivier Benveniste.

I am also in charge of the French National Database for Inflammatory Myopathies and Clinical and Epidemiological Research on Myositis at the Department of Internal Medicine and Clinical Immunology at the GHPS Hospital Group. After working for 13 years in the area of clinical research (in the public and private sector) and obtaining a science doctorate in clinical epidemiology, I started work as Project Manager at the Adult Clinical Trials platform when it was initiated, at the Institute of Myology in July 2019.

To date, we have almost 30 studies that are ongoing or in preparation. These are interventional studies (therapeutic and natural history trials) and observational studies on various types of neuromuscular disease in adults (both acquired – myositis and myasthenia subgroups, and genetic – FSHD, DM1, SMA, LGMD2I). The objective of this platform is to promote the development of research into neuromuscular diseases by allowing, in particular, access to innovative therapies, participation in disease natural history registers and protocols to understand the progression of the diseases and to identify endpoints and therapeutic avenues for future trials.

How is your time being spent in this current crisis situation?
Following the start of the health crisis that we are going through at the moment, the work of the platform was quickly reorganised.

We postponed enrolment in a natural history protocol for patients with limb-girdle muscular dystrophy headed by Dr Tanya Stojkovic at the Department of Neuromyology, and also enrolment in a therapeutic trial to assess the efficacy of an immunosuppressant (rozanolixizumab) in adult patients with generalised myasthenia gravis conducted with the Dr Demeret’s team at the Department of Intensive Care Medicine and Neurological Resuscitation at the GHPS Hospital Group (trial implemented at the start of the COVID-19 epidemic).

The start of therapeutic trials relating to inflammatory myopathies, intended for the spring with the Department of Internal Medicine and Clinical Immunology headed by Prof. Benveniste and at the Institute of Myology, was also postponed to a later date, when the situation will allow it.

The ANSM is also recommending that the relevance of new trials should be assessed and that trials related to treating patients infected with COVID-19 should be prioritised (accelerated procedure for new clinical trial authorisation applications making reference to “COVID-19”). A number of contracts have currently been frozen to allow other trials to be set up, and regulatory submissions have been put on standby.

What organisational measures have you put in place to speed up research and trials for COVID-19?
In response to the COVID-19 pandemic, we were urgently approached by Prof. Benveniste, supported by Prof. Fontaine and the Clinical Research and Innovation Delegation (the DRCI) to provide help with investigation for the CORIMMUNO-19 trial. This trial is assessing the benefit/risk balance for various treatments (different therapeutic targets/strategies – Tocilizumab and Sarilumab, Janus kinase inhibitors and antiretrovirals) on a cohort of patients hospitalised for SARS-CoV-2 infection.

Around 20 volunteers, doctors, research directors, engineers and doctorate students have answered this call and have joined the clinical research associates, partly reassigned to manage this emergency. We have organised the volunteers with the implementation of volunteer agreements with the DRCI (Clinical Research and Innovation Delegation) and the on-site research directorate, the review of the administrative set-up and a request for access to the information systems and to the study electronic case report with the Pitié-Salpêtrière Clinical Research Unit.

These requests were dealt with very quickly and as a matter of priority. Since the beginning of April, we have established seven-day-a-week schedules with the volunteers to keep pace with the inclusions and the requirements of this study/the investigators (daily follow-up with Dr Vauthier). We have trained them in good clinical practices, and in entering clinical and laboratory data for patients into the electronic case report form.
The data entered in real-time are currently being analysed and the first results for 129 randomised patients are encouraging for Tocilizumab (for ventilator-free or non-invasive survival at D14).

What difficulties have you encountered and how did you overcome these?
The first difficulty was organising everything under emergency conditions and putting all the administrative documents in place in record time so that the volunteers could work, by creating a specific contract for them using a volunteer agreement.

The epidemic has now spiked and is beginning to decline, but we remain highly mobilised and stand in solidarity with the care teams, with a common need and will to act for the benefit of clinical research, which remains critical in this situation. We are seeing real team cohesion and ideal conditions exist to successfully complete clinical research at every level. We have all the required skills and players gathered together to successfully complete this project.

Why is clinical research important in response to this type of epidemic?
In parallel with these research projects, relating to the current epidemic, I am also working with Prof. Benveniste on an observational study to assess the protective effect of rapamycin (sirolimus) during the “COVID-19” pandemic (RAPACOVID). This is an immunosuppressant treatment repositioned to treat inclusion body myositis.

It is an example of translational research stemming from fundamental research work conducted by Dr Allenbach and Prof. Benveniste on the preventive and curative effect of rapamycin on a myositis mouse model. This has led to a first therapeutic trial, showing a promising effect of rapamycin treatment in patients with inclusion body myositis (RAPAMI, NCT02481453).
Recent studies have shown that rapamycin could be a candidate drug for COVID-19 infection, due to its protective properties. Indeed, rapamycin shows beneficial effects on coronavirus viral replication regulation, and also on severe pneumonia and acute respiratory involvement in patients infected with H1N1.
Since the conduct of the RAPAMI trial, we have been following a cohort of more than 100 patients with inclusion body myositis being treated with rapamycin, and we will study whether rapamycin protects patients from the infection and/or the development of severe forms of the disease caused by COVID-19.

Finally, new projects are emerging and taking shape regarding the multidimensional impact of COVID-19 in patients with neuromuscular disease (care, diagnosis, disease characterisation and progression, quality of life and psychology). The studies are in the process of being written up and combine the expertise of neurologists in the Service of Neuro-Myology (Dr Evangelista, Prof. Fontaine, Dr Querin), researchers at the Research Centre (Dr Furling), the Neuromuscular Physiology Laboratory (Dr Hogrel, , Dr Bachasson) and the NMR laboratory headed by Dr Marty and Dr Reyngould.
We will assist them with Dr Querin in supporting these projects that are essential to understanding, preparing for and facing new epidemics, especially the management (care and research) of patients with neuromuscular disease.

What message would you like to convey?
This crisis has really helped us to rethink our way of working and to push our limits. It is demanding, but at the same time very exciting and a rich experience. It is a beautiful human and professional adventure, uniting us all in our desire to learn ever more in the service of science.