Dupuytren's disease MedDRA version: 20.0 Level: PT Classification code 10013872 Term: Dupuytren's contracture System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Humira
Product Name: Adalimumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Adalimumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Conc
Sponsors
University of Oxford, Clinical Trials and Research Governance
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Participant is willing and able to give informed consent for participation in the study. • Male or Female, aged 18 years or above. • Part 1: Diagnosed with DD affecting the fingers resulting in flexion deformities of =30° at the metacarpophalangeal joint and or the proximal interphalangeal joint with impaired hand function and awaiting surgery. or Part 2: Patients with early disease nodules who also show 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. Acceptable methods of contraception include: a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods), injectables, the combined oral contraceptive pill (at a stable dose for at least 3 months before entering the study), an intrauterine device, vasectomised partner, or true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant). • Participant results from safety screening tests within normal ranges within 12 weeks of enrolment, with the exception that an earlier clear CXR result may be used where this is in accordance with the time frames of local standard procedures for anti-TNF screening. • 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 78
Exclusion criteria
Exclusion criteria: • Part 1: Participant has previously had fasciectomy, dermofasciectomy, needle fasciotomy, collagenase injection, steroid injection or radiotherapy to treat Dupuytren’s disease in the digit concerned. or • Part 2: Participant has previously had fasciectomy, dermofasciectomy, needle fasciotomy, collagenase injection, steroid injection to the digit to be treated or radiotherapy 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. • Part 1. Scheduled elective surgery or other procedures requiring general anaesthesia during the study other than the scheduled Dupuytren’s surgery • 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. • Part 1: Being treated with anticoagulants, including warfarin. • Have known lung fibrosis (thickening of lung tissue). • Being treated with concomitant biologic DMARDS. • Have received a live vaccine within the previous 4 weeks. Patients may receive concurrent vaccinations but must avoid the use of live vaccines for 12 weeks after their last injection. • Part 2. Patients at risk of Hepatitis B infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To establish an effective dose of adalimumab for downregulating the myofibroblast phenotype in participants with Dupuytren’s disease. Part 2: To determine if injection with adalimumab is superior to placebo injection of normal saline in controlling disease progression in participants with early Dupuytren’s disease. ;Secondary Objective: Part 1. To determine the safety and effectiveness of the drug being investigated in patients with Dupuytren’s disease using laboratory analysis of tissue, clinical assessment and questionnaires. Part 2. To compare the development of early Dupuytren’s disease, flexion deformities of the fingers and impairment of hand function for patients on each treatment using clinical assessments and questionnaires. To assess the acceptability of injections to patients and to monitor for adverse events. ;Primary end point(s): Part 1. Laboratory analysis of tissue: Expression of mRNA for a-SMA from patients on each treatment (IMP or placebo). Part 2. Change in hardness of selected nodule for participants on each treatment baseline and 12 months after first treatment ;Timepoint(s) of evaluation of this end point: Part 1. Dupuytren’s tissue excised during surgery at 12-18 days post-injection will be examined. Part 2. 12 months after first treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: 1. Expression of mRNA for COL-1A1, COL-3A1 and cadherin 11 2. Levels of a-SMA and collagen proteins. 3. Hardness of selected nodule 4. Ultrasound imaging of nodule size. 5. Adverse event assessment comparing active and placebo groups using visual inspection of injection site, surgery site and laboratory reports. 6. Visual assessment of surgical wounds using hand photographs of all participants on each treatment. Part 2: 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. Injection experience 8. Adverse event monitoring comparing active and placebo groups using visual inspection of injection site ;Timepoint(s) of evaluation of this end point: Part 1: 1 and 2. Analysis of tissue removed during surgery at 12-18 days post-treatment. 3 and 4. Measured before treatment and at 2 weeks post-treatment. 5. Observation at each research visit. Injection site assessment immediately after injection and 2 weeks later. Health check phone call 1 week post treatment. Surgery site assessment at 2 weeks post-surgery. 6. 2 and 4 weeks post surgery. Part 2: 1. At 3,6, 9 & 18 months after first treatment. 2, 3, 4 and 5. Before, and at 3, 6, 9, 12 and 18 months after first treatment. 6. During the 18 month post first treatment. 7. After each injection at baseline, 3, 6 and 9 months. 9. Observation at week 0 and 3, 6, 9 and 12 months. | — |
Countries
United Kingdom
Outcome results
None listed