Osteoarthritis of the knee causes persistent pain, stiffness and loss of mobility for millions of people, yet treatment options remain limited. Researchers at the NIHR Leeds Biomedical Research Centre (BRC) and the University of Leeds led an international phase 2 trial of LEVI-04, a new therapy that reduces pain and stiffness and improves function in people with moderate to severe knee osteoarthritis.
Our goal
We wanted to develop safer, more effective treatments for osteoarthritis pain so people can stay active, independent and well for longer. Current options often do not control symptoms well enough and some previous drug approaches have raised concerns about joint safety.
Our approach
Collaborating with our industry partner, Levicept Ltd a UK-based biotechnology company, researchers from the BRC Musculoskeletal Disease Theme helped lead a randomised, double-blind, placebo-controlled phase 2 trial of LEVI-04, a first-in-class therapy designed to block neurotrophin-3, one of the proteins involved in pain signalling.
The 20-week international trial enrolled 518 people with painful, radiographically confirmed knee osteoarthritis across sites in Europe and Hong Kong. Participants received placebo or one of three doses of LEVI-04 every four weeks to week 16, with the main outcome measured at week 17.
Real World Impact
Improving pain, stiffness and daily function
The trial, published in The Lancet in March 2026, showed statistically significant improvements in pain and other key outcomes compared with placebo. More than half of treated participants reported at least a 50% reduction in pain, and more than a quarter reported at least a 75% reduction at weeks 5 and 17.
A potentially safer option
An important finding was that LEVI-04 was well tolerated in this phase 2 study. Researchers reported no increase in serious adverse events, treatment-emergent adverse events or joint pathologies compared with placebo. That matters because earlier pain-targeting approaches in osteoarthritis have been linked to joint safety concerns.
Potential for disease modification
Subsequent preliminary data shared at the American College of Rheumatology conference in 2025 showed that LEVI-04 had positive dose-dependent effects on the size and presence of bone marrow lesions (MRI-detected areas of bone fibrosis and microfractures which are a common feature of osteoarthritis) compared to placebo, suggesting LEVI-04 may have structure modifying properties in addition to analgesic properties.
Leeds research leading international progress
The study was led by Professor Philip Conaghan, Director of NIHR Leeds BRC, Professor of Musculoskeletal Medicine at the University of Leeds and Honorary Consultant Rheumatologist at Leeds Teaching Hospitals NHS Trust. The work highlights Leeds’ role in bringing promising new therapies from experimental science into patient-focused clinical trials.
What’s Next
These findings are an important step forward and LEVI-04 is being evaluated and larger phase 3 trials are planned. The next stage will be to confirm how well the treatment works, how durable the benefits are and which patients are most likely to benefit.
If successful in later-stage trials, this new class of therapy could widen treatment options for people with knee osteoarthritis and reduce the burden of pain, disability and reliance on health services. This is exactly the kind of translational research the BRC exists to support, turning scientific discovery into real benefits for patients.