The INNODIA project’s clinical trial master protocol means launching new clinical trials for drugs to cure type 1 diabetes will be faster and easier.
Type 1 diabetes occurs when the immune system attacks the beta cells in the pancreas that make the hormone insulin, which helps to control blood sugar levels. Currently, people with diabetes manage their condition by regularly measuring their blood sugar levels and injecting themselves with insulin. The good news is that a number of drugs are available, or being developed, that could preserve the beta cells, prevent the disease, and put an end to the constant cycle of blood sugar checks and injections. However, launching clinical trials to test these drugs in newly-diagnosed patients is slow and complicated.
Before a trial can start, the organisers have to submit the protocol of their study to regulatory authorities for approval. The protocol details how the trial will be carried out (e.g. the goal of the trial, how patients would be recruited, what tests they would undergo and when, etc.). It also describes the drug that will be tested in the trial.
To speed up the process, INNODIA has developed a master protocol for certain clinical trials of treatments that could potentially stop type 1 diabetes. ‘The idea of a master protocol is that rather than starting off with a new protocol every time you want to do one of these studies, you have a protocol that can be re-used for different studies – a recyclable protocol,’ explains David Dunger, who is a professor of paediatrics at the University of Cambridge and led INNODIA’s work on the master protocol. The basic design would always be the same, but what would change would be the annex describing the drug (or drugs) under investigation and the minor modifications needed to assess safety and efficacy .
The INNODIA clinical trial master protocol is specifically designed for phase 2 clinical trials of people who have just been diagnosed with type 1 diabetes. Phase 2 trials assess how well a drug works and what the best dose is, as well as the safety profile of the drug. The master protocol also allows for so-called ‘adaptive trials’, in which different drugs (or different doses of the same drug) can be tested in parallel.
Most significantly, the European Medicines Agency (EMA) has given its green light to the master protocol, something that Professor Dunger describes as ‘a major step forward’.
INNODIA is now set to use the protocol for its own clinical trials. The first will focus on a treatment called anti-thymocyte globulin (ATG), a Sanofi product. A previous trial showed that ATG dramatically improves the function of the insulin-producing cells in the pancreas for up to two years from diagnosis. 'What INNODIA plans to do is run an adaptive trial to determine if a lower dose produces the same result,' explains Sanofi's Dr Anke Schulte. 'In this adaptive part, some people will receive the same dose as the previous ATG trial, some will receive placebo, and other groups will go onto different, lower doses to see if they’re equally effective at protecting the insulin-producing cells and so stopping the progression of the disease.'
‘Complex adaptive designs are very suitable to get to the right answer quicker, rather than do one study with one dose, then start all over again with a lower or higher dose to try and find out which is the best way forwards,’ says Professor Dunger. The team also plans to see if ATG works for younger patients (i.e. in children as young as 7 years).
Patients play a central role in INNODIA’s work and Professor Dunger describes the Patient Advisory Committee’s work on the master protocol as ‘fantastic’. He also emphasises the benefits for patients of using a master protocol to set up clinical trials.
‘I think the message for the patients is that in the future we will see a very much better organised and timely way of doing studies, which will get more studies done, quicker, and coming up with the right drugs,’ he concludes.
The ATG trial is part of INNODIA’s wider efforts to better understand type 1 diabetes – information that is essential if we are to develop a cure. So far, the project has enrolled over 3 500 people newly diagnosed with type 1 diabetes, and relatives at high risk for the development of the disease, into a long-term study to investigate how the disease progresses in over time. The design of the long-term studies and the potential to find new markers of disease progression informed the design of the master protocol.
At the time of writing, as with so many other clinical studies, much of INNODIA’s work has had to be paused due to the coronavirus outbreak. In a video message, project coordinator Professor Chantal Mathieu of the University of Leuven told the project’s investigators and participants:
‘One day, we will restart our activities, and then we must hit the ground running. We expect after the summer the start of at least three clinical trials in people with newly-diagnosed type 1 diabetes. I want all of you to know that although our sample collection is now paused, and most of our research laboratories have had to close, we, the INNODIA scientists and clinical teams are not resting. We keep working hard and preparing the future. We will overcome this and come out stronger in the end.’
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Watch Chantal Mathieu’s video message