A Multi-centre, Double Blind, Randomised, Placebo-controlled, Parallel Group, Phase II Trial to Determine the Efficacy of Intra-nodular Injection of Anti-TNF to Control Disease Progression in Early Dupuytren's Disease, With a Dose Response.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 3
- 主要终点
- Early Disease: Nodule Hardness at 12 Months
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
During Dose Response part of the trial the Investigator will be blinded. During the Early Disease part of the trial the Investigator will not be blinded but will not carry out any outcome assessments.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is willing and able to give informed consent for participation in the study.
- •Male or Female, aged 18 years or above.
- •For 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 for Part 2: 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. 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 chest x-ray 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.
排除标准
- •For 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 for 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.
- •For Part 1: Scheduled elective surgery or other procedures requiring general anaesthesia during the study other than the scheduled Dupuytren's surgery. Or for Part 2: Scheduled elective surgery or other procedures requiring general anaesthesia during the study
- •Participant who has ever been diagnosed with cancer, is terminally ill or is inappropriate for placebo medication
- •Systemic inflammatory disorder such as rheumatoid arthritis (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 coumarin anticoagulants, such as 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. Participants may receive concurrent vaccinations but must avoid the use of live vaccines for 12 weeks after their last injection.
- •Part1: Have received parenteral steroid within the previous 6 weeks.
- •Part 2: Participants at risk of Hepatitis B infection.
研究组 & 干预措施
Anti-TNF
adalimumab
干预措施: Adalimumab (Drug)
Placebo
saline
干预措施: Saline (Drug)
结局指标
主要结局
Early Disease: Nodule Hardness at 12 Months
时间窗: 12 months
Tonometry - A hardness score in arbitrary units with 0 being the lowest hardness and 100 being the greatest hardness units on a scale.
次要结局
- Early Disease: Grip Strength(12 months)
- Early Disease: Extension Deficit of Affected Joint(12 months)
- Early Disease: Patient Reported Outcomes(12 months)
- Early Disease: Nodule Size(12 months)