Gisli sat down with the PACT team to talk about the upcoming Randomised, Embedded, Multifactorial, Adaptive, Platform (REMAP) trial for interstitial lung disease (ILD), including how it started, what the team hopes it will achieve and the challenges they’ve faced.
Tell us a bit about yourself and why you chose PF as your research area:
I am Professor Gisli Jenkins, the Margaret Turner-Warwick Chair of Thoracic Medicine at Imperial College, London. I also lead the Margaret Turner-Warwick Centre for Fibrosing Interstitial Lung Diseases at Imperial College London and I am a Consultant ILD physician at the Royal Brompton Hospital. The Margaret Turner-Warwick Centre for Pulmonary Fibrosis is named after Dame Margaret Turner-Warwick who was an early pioneer into understanding and improving care for patients with Interstitial Lung Diseases. The centre covers the whole translational pipeline from genetics, fundamental biology, data analytics as well as observational and interventional clinical trials.
I have been researching pulmonary fibrosis since 1997 since I worked in Professor Geoffrey Laurent’s laboratory at University College London. I started researching pulmonary fibrosis for a number of reasons, both personal and professional. Some of my family members had suffered with Interstitial Lung Disease, and pulmonary fibrosis was at the time, and remains and area of high unmet need. Professor Laurent, a proud Western Australian, was a major inspiration for me and he is a major reason I have continued my research into pulmonary fibrosis over the last 25 years.
Describe your clinical trial in a couple of sentences:
This trial is a Randomised Embedded Adaptive Multi-factorial Platform trial in Interstitial Lung Disease (REMAP-ILD). This sort of trial has a large number of efficiencies including generating a Platform that enables therapies to be evaluated more quickly, Response Adaptive Randomisation that ensures that ineffective studies are halted promptly and patients are concentrated into domains where therapies are more likely to be effective, and most importantly embedding in to routine clinical practice that ensures results are generalisable and all patients get access to best care.
Tell us how this trial came about:
REMAP-ILD came about from Twitter discussions with Dr Letitia Kawano-Dourado (Brazil) and Professor Naftali Kaminski (USA) who were discussing Bayesian Adaptive trials. I had been considering the strategic development of anti-fibrotic therapies and considered that 10 years from start of phase 2 to delivery of ‘successful’ phase 3 was too long for my patients to wait. Having seen the success of platform trials at first hand during the COVID pandemic we decided the time was now to try this approach in Interstitial Lung Diseases.
What do you hope this trial will achieve?
I hope we will see greater inclusivity and diversity in patient recruitment that will lead to better generalisability of results. Through taking seamless phase 2/3 approach we will reach stop ineffective therapies more rapidly than previously. Most importantly I expect we will see more rapid assessment of interventions, including repurposed and novel therapies, leading to practice changing introduction of evidence-based therapy.
What has been the biggest challenge of the trial so far?
This is the most ambitious project I have ever been involved with. The biggest challenge is trying to package this massive global bite sized pieces that will make it deliverable in a practical and meaningful fashion.
The people working on this trial are:
Clinical Researchers in progressive pulmonary fibrosis around the world including North and South America, UK and Europe, India, Middle East and Australia, a team of Bayesian Statisticians at Berry Consultants, a team of statisticians at Imperial Clinical Trials Unit, UK and patient organisations and representatives. We are currently building the REMAP-ILD Consortium and welcome new international partners.
What do you see as the biggest evidence gaps in PF care? What are the clinical research priorities?
There are four broad areas in need of improved evidence: 1) early and accurate diagnosis; 2) development of effective treatments; 3) enabling patients, carers and families to live well for longer; and 4) understanding of the biological basis of pulmonary fibrosis. The first three are primary clinical research priorities and further detail has been provided by the Action for Pulmonary Fibrosis-James Lind Alliance top 10 research priorities, which include four that will be directly covered by REMAP-ILD including the second highest priority “Can new treatments other than pirfenidone and nintedanib slow, halt or reverse the progression of PPF?” and the fifth highest priority “What are the best ways (drug, non-drug and aids) to treat cough in PPF?”. However, as a clinician scientist, I also firmly believe that our best approach to stopping, or better still reversing fibrosis, is through improved understanding of fibrosis biology and targeting the aberrant processes that cause the development of pulmonary fibrosis in the first place.