Safety of abatacept in Rheumatoid Arthritis associated Interstitial Lung Disease

• Register: EUCTR
• Last refreshed on: 28 May 2018
• Main ID: EUCTR2016-002569-68-GB
• Date of registration: 18/05/2018
• Prospective Registration: No
• Primary sponsor: Cambridge University Hospitals NHS Foundation Trust
• Public title: Safety of abatacept in Rheumatoid Arthritis associated Interstitial Lung Disease
• Scientific title: Safety of abatacept in Rheumatoid Arthritis associated Interstitial Lung Disease: A feasibility study - APRIL
• Date of first enrolment: 04/05/2018
• Target sample size: 30
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002569-68
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Carrie Bayliss
• Affiliation: Cambridge Clinical Trials Unit

• Name: Carrie Bayliss
• Affiliation: Cambridge Clinical Trials Unit

Key inclusion & exclusion criteria

Inclusion criteria:
• Aged 18 years or over (for patients aged 65 and over, additional caution should be taken to assess their health status prior to inclusion)
• 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 not responded to conventional immunosuppressive therapy, or has progressed over 24 weeks, regardless of the severity of the ILD at the time of inclusion to the trial. Progression will be defined as EITHER a decrease in either FVC or DLCOc by at least 5% over 6 months or 10% over 12 months (or by (0.83 x m)%, where m =number of months’ interval between a pair of lung function tests done within the last 18 months) OR progression of lung fibrosis on a high-resolution CT chest, as reported by a chest radiologist.

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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
The presence of any of the following will preclude patient participant inclusion:
• Unable to provide written informed 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 time of recruitment 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 < 70%.
• 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid-associated Interstitial Lung Disease (RA-ILD)
MedDRA version: 20.0 Level: PT Classification code 10022611 Term: Interstitial lung disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 20.0 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Orencia
Product Name: Orencia
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: ABATACEPT
CAS Number: 3 332348-12
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: up to
Concentration number: 10-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Evaluation at week 24 (following 20 weeks of treatment with abatacept)

Secondary Objective: The secondary objectives of this trial study are to assess changes in the following outcome measures (within the first 20 weeks of treatment);
1. Diffusing capacity of the lung for carbon monoxide (DLCO).
2. Patient-reported disability associated with dyspnoea (using the MRC dyspnoea grade)
3. Patient-reported health status related to ILD (using the King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire)
4. The Disease Activity Score (28 joints) (DAS28) score
5. The radiological appearances of the ILD, based on semi-quantitative scoring of CT Chest appearances
6. Average resting oxygen saturation levels
7. Cough score (using the Leicester Cough Questionnaire)
8. Overall health status, taking into account the EQ-5D
9. Number of Respiratory tract infections

Exploratory objectives
The exploratory objectives of this trial are to assess the changes in the following outcome measures (within the first 20 weeks of treatment);
1. Possible biomarkers of RA-ILD assessed using BAL fluid an

Main Objective: To investigate the safety of abatacept in Rheumatoid arthritis (RA) patients with co-morbid interstitial lung disease (ILD) by estimating the change over time in Forced Vital Capacity (FVC) associated with abatacept therapy in RA-ILD.

Primary end point(s): The primary outcome for this study is the change in forced vital capacity (FVC) after 20 weeks of treatment with abatacept.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Evaluation at week 24 (following 20 weeks of treatment with abatacept)

Secondary end point(s): Secondary end points include:
• Diffusing capacity of the lung for carbon monoxide (DLCO)
• MRC dyspnoea score
• Kings Brief Interstitial Lung Disease score (K-BILD)
• Semi-quantitative radiological scoring of the ILD based on CT Chest appearances before and after abatacept
• Resting oxygen saturation
• DAS28
• Leicester Ccough Questionnaire score
• EQ-5D (a standardised measure of health status by the EuroQol group)
• Respiratory tract infection

Exploratory end points
• Biomarker analysis

Secondary ID(s)

APRIL

NCT03084419

Source(s) of Monetary Support

Bristol-Myers Squibb