Prof. Armin Curt and his team have been conducting a Europe-wide phase II clinical trial with NG-101, a recombinant human antibody. NG-101 neutralizes the membrane protein Nogo-A and thus promotes neural repair and functional recovery in patients with acute spinal cord injuries. We spoke to Armin Curt about the results that are now available, as well as challenges such as working in a large European network and the impact of unforeseen events such as Brexit or COVID-19 on such a study.
Hi Armin, you are involved in a multinational clinical study using antibodies to help patients with acute spinal cord injuries. What are the main goals of this study?
The overarching aim of our double-blind phase II trial is to enhance the movement and quality of life for acute traumatic tetraplegic patients and assess the safety and efficacy of the acute treatment with an antibody called NG-101. Additionally, there was a focus on establishing a network with several European Spinal Cord Injury Centers, continuing research into spinal cord injury treatment, forming a biobank for pharmacokinetic studies, applying novel quantitative magnetic resonance imaging (MRI) methods, and establishing statistical methods for treatment effects leading to novel prediction rules.
Moving on to the consortium you’re working within, which spans Europe, how many study centers are involved, and what role does Zurich play in this initiative?
The study involves 14 European Spinal Cord Injury Centers from the EMSCI (European Multicenter Study about Spinal Cord Injury) network, founded in Zurich in 2001. In our study, Zurich serves as the trial coordinator and trial sponsor for the Swiss centers.
How did the idea for this project emerge?
The project stems from a longstanding collaboration between preclinical neuroscience, led by Prof. Martin Schwab, and the Spinal Cord Injury Center Balgrist, under the leadership of Prof. Volker Dietz and me. Preclinical research with animal models led to enhanced axonal regeneration and neuroplasticity after brain and spinal cord injuries. This success prompted the translation of these findings to patients with acute spinal cord injury. A previous phase I clinical study demonstrated the safety and tolerance of the treatment in complete spinal cord injury patients.
What was your personal motivation to get involved in the project?
My daily involvement in the treatment and care of patients with acute para/tetraplegia fueled my desire to contribute to finding a treatment for damaged spinal cords. Over the decades, our confidence in the anti-Nogo-A treatment concept grew, emphasizing the importance of involving specialized spinal cord injury treatment centers in such a project.
Why did the Anti-NOGO Antibody work in a subgroup but not demonstrate substantial improvement among all study participants?
Regenerative treatments like the anti-Nogo-A concept rely on preserved tissue bridges to enable neural fiber sprouting, explaining why patients with complete transected or damaged spinal cords did not show a treatment effect, while those with preserved tissue bridges did. Contrary to the assumption, however, the study did reveal both motor and functional improvements, marking it as the first to exhibit such a profound treatment effect. Treated patients showed over a 25% higher outcome in functional independence.
Now, turning to the challenges faced during the project, what obstacles did you encounter?
The project faced several challenges such as Brexit, which led to relocating the delivery of Investigational Medical Product from England to Germany under standard medical production requirements. Then there was the impact of the COVID-19 pandemic as well as the complexity of obtaining approvals from regulatory authorities. Four countries approved, one did not. This highlights the significant challenges posed by jurisdictional variations in accomplishing a European trial.
These are quite some challenges… How did you make the project a success?
The project has been running for 8 years and is still going strong. Success depends heavily on fruitful collaboration, a strong network and a good measure of perseverance. Perseverance is also needed to overcome unforeseen challenges such as Brexit and the adjustments required due to the COVID-19 pandemic. The support of the Clinical Research Organization and a network of dedicated study nurses are essential. Planning for the next trial is already underway, emphasizing the enduring commitment to advancing spinal cord injury research.
Useful links
- https://nisci-2020.eu
- https://www.balgrist.ch/forschung/forschergruppen/paraplegie/forschungsprojekte
- https://www.emsci.org
- https://scitrialsfinder.net
- https://clinicaltrials.gov
Image: Universitätsklinik Balgrist, Armin Curt with patient