Early phase trial with Medivir
8 April 2021
Led by Professor Philip Conaghan at the Leeds NIHR BRC this research activity was established as a feasible, short term trial to assess osteoarthritis structure modification.
Osteoarthritis (OA) is a significant worldwide problem resulting from ageing and increasingly overweight populations. The disease includes damage to joint-lining cartilage and bone underneath the cartilage. A major unmet need in the field is to develop a therapy that slows the slow structural joint deterioration in OA.
Trials of OA structural progression use x-rays and require several hundred patients per study arm, with patients needing to be followed up over two years. Even with existing more sensitive MRI outcomes, approximately 150 patients per arm is required for a minimum 12 month study. This means structure modifying trials are very expensive, and prohibitively for pharmaceutical companies, an early phase study can take over five years to produce a result.
For many years, Prof Conaghan’s team at Leeds BRC have collaborated with external company Imorphics (Manchester, UK). Through accurate machine learning-derived automated segmentation highly responsive imaging outcomes were produced including bone shape. Medivir, a Sweden based pharmaceutical company, approached Prof Conaghan’s team with a novel cathepsin-K inhibitor. This drug could potentially slow OA structural progression, but needed a study design and outcomes that could be done in a feasible timescale.
The Leeds BRC team supported the development of an early phase two randomised trial in people with knee OA. The trial consisted of 70 patients per arm, three arm (two doses of study drug, one matched placebo). In this multicentre trial, MRI scans were performed at baseline and six months. The study demonstrated a reduction in bone deterioration rates for both doses of the study drug, it did not however, fully show a demonstrable benefit on people’s pain. This was the first time any therapy was shown to reduce rates of bone pathology change in OA. The report results were published in a high impact factor International journal.
Importantly, this study demonstrated drug efficacy. It also demonstrated the feasibility of carrying out smaller and shorter duration structure modification trials in OA. Looking forward, Medivir seek partners to develop their therapy. Prof Conaghan’s BRC team continues to validate their quantitative 3D imaging biomarkers to improve clinical trial design, providing insights into key time points for targeting OA structural progression.