Incubating Big Ideas


Innovative clinical trial design breathes life into potential cell therapy for lung disease in preterm babies

When it comes to developing medical treatments, it is a long, challenging and expensive road from the research lab to the clinic.

Most Canadians give little thought to what goes into the healthcare we receive – we’re happy to get good care when and where we need it. Consider, though, that every medication and procedure you’ve been prescribed, and every machine that was used to monitor or control your body’s functions, faced rigorous tests for safety, effectiveness and accuracy before they could be used in your care. Likely, they were also critically assessed for cost-effectiveness.

Now, consider where to begin when you want to test the first-ever stemcell-based therapy to treat a historically untreatable, complex condition in an incredibly vulnerable population – in this case, chronic lung disease in extremely premature babies. How do you know parents will allow their sick infant to receive an unproven therapy in a clinical trial? How will you know if health systems will be able to afford the treatment?

If you’re Dr. Bernard Thébaud and his team at The Ottawa Hospital, you do your homework.

“The translation of therapies into the clinic often fails for a variety of reasons – flawed early research, various barriers to enrolling enough patients, not taking into account patients’ preferences, failing to consider the required resources to manufacture and deliver the treatment, understanding what the ultimate cost will be, and more,” says Dr. Thébaud, who is also affiliated with CHEO and the University of Ottawa. “We want to mitigate the risk of failure for advanced cell therapies, so we set out to identify obstacles and facilitators ahead of a clinical trial, taking those into account in designing the trial to enhance our chances for success.”

The result is the INCuBATOR project (Innovative Neonatal Cellular Therapy for BPD: Accelerating Translation of Research), funded through a series of OIRM Disease Team grants totalling $638,000 over the last four years from the Ontario Institute of Regenerative Medicine (OIRM). Its ultimate goal is to assess the use of mesenchymal stromal cells (MSC) to treat bronchopulmonary dysplasia (BPD), a chronic lung condition that arises from ventilator and oxygen treatment for breathing failure in premature infants.

Currently, there is no available treatment for BPD, which can damage developing organs, adversely affect the brain and lead to blindness and other lifelong consequences. MSCs, in this case those taken from the umbilical cords of healthy babies at birth (UC-MSCs), have shown promise in animal models as a treatment for various tissue injuries and related immune responses in many chronic lung diseases.

To date, INCuBATOR has produced several important novelties: the first rigorous, systematic reviews of both experimental and clinical evidence for using UC-MSCs in neonatal lung injury – providing a comprehensive understanding of what is known and not known about UC-MSCs in this application. The team also conducted the first detailed economic evaluation of the treatment to ensure it would be economically viable, developing a novel tool to reliably forecast the short- and long-term costs of BPD. They captured an objective assessment of attitudes toward cell therapies and clinical trials in preterm infants by conducting interviews with parents and physicians (neonatologists). Importantly, INCuBATOR researchers were also the first to test the feasibility and safety of intravenous administration of UC-MSCs in a large animal model of neonatal lung injury, results of which will be published soon. A phase 1 trial to test the feasibility and safety of UC-­MSCs in extreme preterm infants is expected to begin in July 2020.

All of these successes were advanced via collaborations with leading Canadian and international organizations, including OIRM, Stem Cell Network, The Ottawa Hospital’s Ottawa Methods Centre and Biotherapeutics Manufacturing Centre, University Health System in San Antonio, Texas, the University of Dresden, Germany, the Center for Regenerative Therapies Dresden and more.

“Because we had all of these unique elements and knowledge in place at The Ottawa Hospital, Health Canada and the hospitals’ research ethics boards were satisfied and granted permission to proceed with the phase-I trial based on the evidence we collected,” Dr. Thebaud adds. “It’s exciting to have the resources in place to develop innovative trial designs and answer not just one, but several key questions at a time.”

Photo: The Ottawa Hospital