Repurposing Anti-TNF for Treating Dupuytren's Disease

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.

Conditions

• Dupuytren's Disease

Interventions

DRUG

Adalimumab

DRUG

Saline

Sponsors & Collaborators

• Department of Health, United Kingdom

  collaborator OTHER_GOV

• Wellcome Trust

  collaborator OTHER

• 180 Therapeutics LP

  collaborator OTHER

• University of Oxford

  lead OTHER

Principal Investigators

• Jagdeep Nanchahal, PhD FRCS · University of Oxford

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-03-02

Primary Completion

2020-11-30

Completion

2020-12-31

Countries

• Netherlands
• United Kingdom

Study Locations