Primary objective: To determine if injection with the optimal dose of adalimumab (40mg) is superior to placebo injection of normal saline in controlling disease progression in patients with early Dupuytren*s disease.Secondary objectives: * To…
Source
Brief title
Condition
- Connective tissue disorders (excl congenital)
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in hardness of selected nodule for participants on each treatment
baseline and 12 months after first treatment..
Secondary outcome
For participants on each treatment.
1.Change in hardness of selected nodule for participants on each treatment at
baseline, 3, 6, 9, 12 & 18 months after first treatment.
2. Ultrasound imaging of nodule size.
3. Range of motion of the affected digit.
4. Grip strength.
5. Participant Reported Outcomes:
Michigan Hand Outcomes Questionnaire (MHQ)
6. Participant identified activity most restricted by DD scored on a scale of
1-10.
7. Progression to surgery of the digit being assessed
8. Injection experience
9. Adverse event monitoring comparing active and placebo groups using visual
inspection of injection site.
Background summary
There is a need to develop an effective therapy to prevent progression of early
Dupuytren*s Disease. This therapy would avoid the necessity for invasive
procedures and also prevents the development of recurrent disease following
surgery, needle fasciotomy or collagenase injection in patients with
established finger contractures.
Adalimumab is an anti-Tumour Necrosis Factor (anti-TNF) drug, approved for use
by the US Food and Drug Administration (FDA) since 2002, and European Medicines
Agency (EMA) since 2003. It is used to treat rheumatoid arthritis, psoriatic
arthritis and ankylosing spondylitis. Verjee et al.(1) demonstrated that
anti-TNF also down-regulates the phenotype of existing myofibroblasts and
prevents the conversion of fibroblasts from the palm of patients with DD into
myofibroblasts.
Therefore, anti TNF/adalimumab could be a valid therapeutic option to prevent
progression and after a recent study to optimize the dose for injection we now
aim to demonstrate the safety and efficacy of adalimumab to treat early DD in a
randomized controlled trial.
Study objective
Primary objective:
To determine if injection with the optimal dose of adalimumab (40mg) is
superior to placebo injection of normal saline in controlling disease
progression in patients with early Dupuytren*s disease.
Secondary objectives:
* To compare the development of Dupuytren*s nodules and associated cord,
flexion deformities of the fingers and impairment of hand function for patients
on each treatment arm.
* To monitor for adverse events.
Tertiary objectives:
* To assess if early DD injection therapy represents good value for money
compared to current clinical care.
* To monitor circulating levels of adalimumab and antibodies to adalimumab in
the blood.
Study design
A multi-centre, double blind, randomised, placebo-controlled, parallel group,
phase II trial
Intervention
4 intra-nodular injections with either Adalimumab 40mg (anti-TNF) or saline
(placebo) over 9 months: at baseline,3,6,9 months with 18 months follow-up. The
ratio Adalimumab: Placebo is 1:1
Study burden and risks
Because of its effects on the immune system, adalimumab may increase
susceptibility to infections and patients are screened for tuberculosis (TB)
and Hepatitis B and C. In common with all anti-TNF drugs, there may be a
slightly increased risk of certain types of cancer, but this link is not proven
and is currently being researched. However, in our study risks should be lower
as anti-TNF will be given at relatively low doses, less frequently and for a
limited duration. A benefit for the patients treated with adalimumab may be
that invasive treatment with surgery or collagenase will be not necessary.
Churchill Drive, Headington block 60
Oxford OX3 7LQ
GB
Churchill Drive, Headington block 60
Oxford OX3 7LQ
GB
Listed location countries
Age
Inclusion criteria
* Participant is willing and able to give informed consent for participation in the study.
* Male or Female, aged 18 years or above.
* Participants with early disease nodules who have shown or reported progression of the disease in the previous 6 months with flexion deformities of their fingers of *30° at the metacarpophalangeal and/or at the proximal interphalangeal joint, i.e. total flexion deformity of up to 60°.
* The DD nodule to be treated must be distinct and identifiable.
* Female participants of child bearing potential, and male participants whose partner is of child bearing potential, must be willing to ensure that they or their partner use effective contraception throughout the treatment period and for 5 months following the last research injection.
* Participant results from safety screening tests within normal ranges within 12 weeks of enrolment.
* Able (in the Investigators opinion) and willing to comply with all study requirements.
* Willing to allow his or her general practitioner to be notified of participation in the study.
* Sufficient language fluency to ensure informed consent is obtained and to complete the questionnaires pertaining to hand function.
Exclusion criteria
* Participant has previously had fasciectomy, dermofasciectomy, needle fasciotomy, collagenase injection, steroid injection to the digit to be treated or radiotherapy to to treat Dupuytren's disease in the hand concerned.
* Female participant who is pregnant, lactating or planning pregnancy during the course of the study and for 5 months following last injection.
* Male participant who is planning a pregnancy during the course of the study and for 5 months following last injection.
* Significant renal or hepatic impairment.
* Participant who has ever been diagnosed with cancer, is terminally ill or is inappropriate for placebo medication.
* Systemic inflammatory disorder such as RA or inflammatory bowel disease.
* Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant*s ability to participate in the study.
* Participated in another research study involving an investigational medicinal product in the past 12 weeks.
* Known allergy to any anti-TNF agent.
* Have HIV or hepatitis B or C.
* Known to have an infection or history of repeated infections.
* History of Tuberculosis (TB).
* Have Multiple Sclerosis (MS) or other demyelinating disease.
* History of local injection site reactions.
* Needle phobia.
* Have moderate or severe heart failure.
* Have known lung fibrosis (thickening of lung tissue).
* Being treated with concomitant biologic DMARDS.
* Have received a live vaccine within the previous 4 weeks. Participants may receive concurrent vaccinations but must avoid the use of live vaccines for 12 weeks after their last injection.
* Patients at risk of Hepatitis B infection.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2015-001780-40-NL |
ISRCTN | ISRCTN27786905 |
CCMO | NL60350.042.18 |