Repurposing Anti-TNF for Treating Dupuytren's Disease
Status:
Completed
Trial end date:
2020-12-01
Target enrollment:
Participant gender:
Summary
Dupuytren's disease is a very common condition, affecting 4% of the general UK and US
population. It causes the fingers to curl irreversibly into the palm and can be extremely
disabling. The disease usually starts as a small firm lump (nodule) in the palm, and in about
40% of patients advances to form cords that pull the fingers into the palm. There is no
approved treatment for the early stage of disease. Once patients have established
deformities, the diseased tissue can removed by surgery or cut using less invasive techniques
such as a needle or an enzyme. However, recovery following surgery usually takes several
months and recurrence rates with the less invasive techniques are high.
The investigators have unravelled the cellular process that initiates and maintains the
disease progress and identified tumour necrosis factor (TNF) as a new target for treatment.
Based on these findings the investigators plan to test the effects of adalimumab, an anti-TNF
drug which currently approved for use in patients with rheumatoid arthritis and other
inflammatory conditions. The aim of the study is to find out whether treatment by injection
with adalimumab directly into the diseased tissue will control the advance of early
Dupuytren's disease better than a placebo injection with normal saline.
The investigators will first carry out a small trial in up to 40 patients with established
disease to determine the best dose that reduces the activity of the cells responsible for the
disorder (Dose Response study). In this part patients who will be having surgery to remove
their diseased tissue will receive a single injection of adalimumab into the nodule in their
hand about 2 weeks before surgery. The tissue that is then removed during surgery will be
analysed in the investigator's laboratories to determine the effect of the drug on the
tissue. Patients will be followed for 12 weeks after surgery.
In the second part of the study the investigators will assess whether the optimal dose of the
drug prevents early disease advancing in 138 patients (Early Disease study). Patients who
take part in the second part of the study will receive a total of 4 injections of adalimumab
into the nodule in their hand at three monthly intervals. They will then be checked at 3 & 9
months after the last injection. In additional to assessing the effect of the injections on
the nodule and hand function, information will also be collected to assess the cost
effectiveness of the treatment.
Phase:
Phase 2
Details
Lead Sponsor:
University of Oxford
Collaborators:
180 Therapeutics LP Department of Health, United Kingdom Wellcome Trust