Repurposing anti-TNF for treating Dupuytren's disease
Research type
Research Study
Full title
A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial to determine the safety and efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with a dose response run-in.
IRAS ID
157365
Contact name
Jagdeep Nanchahal
Contact email
Sponsor organisation
University of Oxford, Clinical Trials and Research Governance
Eudract number
2015-001780-40
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Summary of Research
Dupuytren's disease is a very common condition that causes the fingers to curl into the palm and can be extremely debilitating. In early disease hard nodules develop in the palm. There is no approved treatment for early disease. Once patients have established deformities, the diseased tissue can be removed surgically or cut using less invasive techniques such as a needle or an injection of an enzyme. However, recovery following surgery usually takes several months and the recurrence rates with the non-surgical techniques are high.
We have unravelled the molecular mechanisms that start and maintain the disease process. Based on these findings we plan to test a drug currently approved for use in patients with rheumatoid arthritis. The drug will be injected directly into the diseased tissues in the palm to maximise it's effect. We will first conduct a small trial in 40 patients with established disease to determine the best dose inhibiting the activity of the cells responsible for the disorder (Part 1). Next we will assess whether the drug at this dose prevents progression in 138 patients with early disease (Part 2). If effective, this will represent the first targeted therapy involving a simple injection for patient's with early Dupuytren's disease that will preserve hand function and avoid the need for surgery.
Summary of Results
Currently there is no approved treatment for early stage Dupuytren’s disease. We identified Tumor Necrosis Factor (TNF) as a potential therapeutic target. In our phase 2a dose-ranging clinical trial we identified the optimal dose and formulation of adalimumab, the anti-TNF agent we are using. In the phase 2b clinical trial we randomised participants 1:1 to receive 4 injections at 3 monthly intervals of either adalimumab or saline (placebo). Our primary outcome was looking at decrease in nodule hardness (measured using an instrument called a durometer) at 12 months. We met this primary endpoint of decrease in nodule hardness and the secondary outcome of decrease in nodule size on ultrasound scan, with statistically significant differences.
REC name
South Central - Oxford B Research Ethics Committee
REC reference
15/SC/0259
Date of REC Opinion
14 May 2015
REC opinion
Favourable Opinion