Safety of Abatacept in Rheumatoid Arthritis Associated Interstitial Lung Disease: A Feasibility Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Forced Vital Capacity (FVC)
研究概览
简要总结
Early initiation of treatment for Rheumatoid arthritis (RA) can prevent several of the long term problems associated with the condition. However, many RA patients develop lung inflammation and scarring, called 'interstitial lung disease' (RA-ILD), contributing to early death in 1 in 5 people. There is no proven treatment for these patients and some medications for RA can in fact worsen their lung disease. There is a need therefore to find safe medications that can not only control RA joint disease, but also prevent progression of RA-ILD. Abatacept is an approved drug for treating RA and is used widely. It is a newer RA medication, with a unique mechanism of action, and it has been shown to prevent progression of joint damage and improve physical function. The investigators aim to assess the safety of this medication in patients with RA-ILD and improve our understanding of the mechanism of lung damage in rheumatoid disease.
The investigators will perform a small clinical trial to assess the feasibility of performing a larger randomized controlled trial. A total of 30 patients with RA-ILD will be treated with abatacept infusions fortnightly for the first month, then every 4 weeks for a total of 20 weeks. In order to be eligible for the study, a patient must be able to provide written informed consent, be aged ≥18 years, and have interstitial lung disease that has not responded to or progressed over 6 months despite conventional immunosuppression. Change in lung function (forced vital capacity) at 24 weeks will be evaluated. To assess the mechanisms that may be involved with the development of ILD, the investigators will assess the effects of abatacept on biomarkers obtained from the blood and the lung (bronchoalveolar lavage), including markers of infection (the lung microbiome).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Aged 18 years or over
- •Agree to use 2 acceptable forms of effective contraception for the duration of the study trial and a further 14 weeks after completion
- •Meet a diagnosis of RA by 2010 EULAR/ACR criteria
- •Have interstitial lung disease associated with RA, with supportive findings on their PFTs and CT Chest scans. Participants will be included if their ILD has progressed over 14 months. Progression will be defined as EITHER:
- •A decrease in FVC by at least 5% when comparing two sets of PFTs done in the last 24 months, but with an interval of up to 14 months between the PFTs OR
- •Progression of lung fibrosis on a high-resolution CT chest, as reported by a chest radiologist.
排除标准
- •Unable to provide informed written consent
- •Participants who are taking other immunosuppressants, e.g. mycophenolate mofetil (MMF), unless this has been discontinued with an adequate washout period. The exceptions to this exclusion criterion are methotrexate (MTX) and hydroxychloroquine, which are allowed provided the dose has been stable for 6 weeks prior to baseline (visit 2).
- •Participants who have been taking > 10mg Prednisolone daily within the last 6 weeks prior to baseline (visit 2)
- •Participants who have had rituximab, within the 24 weeks prior to baseline (Visit 2)
- •Any participant with active signs or symptoms of infection at the baseline (visit 2) or requiring antibiotic treatment within the preceding 4 weeks
- •Any participant with significant co-existing lung disease, such as asthma, bronchiectasis, emphysema, Chronic Obstructive Pulmonary Disease (COPD) or if their pre-bronchodilator FEV1/FVC ratio is < 60%.
- •Significant other co-morbidity (e.g. active malignancy/liver disease/renal disease) within the last 5 years
- •Prior use of abatacept at any time
- •Participation in any other clinical trial within 8 weeks or 5 half-lives of IMP, whichever is longer, prior to baseline (visit 2) (participation in 'observational' studies is allowed)
- •Hypersensitivity to any excipients of abatacept
- •Any participant who has had live vaccines within 6 weeks prior to baseline (Visit 2)
- •Participant is pregnant or breastfeeding
研究组 & 干预措施
Abatacept in patients with RA-ILD
Thirty participants with RA-ILD will be treated with abatacept infusions, which will be given fortnightly for the first 4 weeks, then every 4 weeks for a total of 20 weeks.
干预措施: Abatacept (Drug)
结局指标
主要结局
Forced Vital Capacity (FVC)
时间窗: 28 weeks (Screening-V9)
Assessing the change of Forced Vital Capacity (FVC) across screening, baseline V2 (prior to abatacept), V6 and V9.
次要结局
- MRC dyspnoea score(24 weeks (Baseline-V9))
- Kings Brief Interstitial Lung Disease score (K-BILD)(24 weeks (Baseline-V9))
- Semi-quantitative radiological scoring of the ILD(28 weeks (Screening-V9))
- Leicester Cough Questionnaire score(24 weeks (Baseline-V9))
- EQ-5D(24 weeks (Baseline-V9))
- Transfer factor of the lung for carbon monoxide (TLCO)(28 weeks (Screening-V9))
- DAS28(28 weeks)
- Resting oxygen saturation(28 weeks)
- Respiratory tract infection(24 weeks (Baseline-V9))
研究者
Frances Hall
Consultant Rheumatologistand and Clinical Lead for Connective Tissue Disease
Cambridge University Hospitals NHS Foundation Trust