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APRIL (AbatacePt in Rheumatoid Arthritis-ILD) (APRIL)

Primary Purpose

Rheumatoid Arthritis, Interstitial Lung Disease

Status

Unknown status

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Abatacept

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Interstitial Lung Disease, RA-ILD, Abatacept

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Addenbrookes HospitalRecruiting
Papworth HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Abatacept in patients with RA-ILD

Arm Description

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.

Outcomes

Primary Outcome Measures

Forced Vital Capacity (FVC)

Assessing the change of Forced Vital Capacity (FVC) across screening, baseline V2 (prior to abatacept), V6 and V9.

Secondary Outcome Measures

Transfer factor of the lung for carbon monoxide (TLCO)

Assessing the change of Transfer factor of the lung for carbon monoxide (TLCO) at screening (prior to abatacept), V6 and V9.

MRC dyspnoea score

Assessing the change of MRC dyspnoea score completed at Baseline V2 (prior to abatacept), V6, V9

Kings Brief Interstitial Lung Disease score (K-BILD)

Assessing the change of Kings Brief Interstitial Lung Disease score (K-BILD) questionnaire completed at Baseline V2 (prior to abatacept), V6, V9

Semi-quantitative radiological scoring of the ILD

Assessing the change of HRCT chest scans performed at screening (prior to abatacept and V9 (end of trial)

Resting oxygen saturation

Resting oxygen saturation recorded at all visits

DAS28

DAS28 recorded at all visits

Leicester Cough Questionnaire score

Assessing the change of Leicester Cough Questionnaire completed at Baseline V2 (prior to abatacept), V6, V9

EQ-5D

Assessing the change of EQ-5D Questionnaire completed at Baseline V2 (prior to abatacept), V6, V9

Respiratory tract infection

Assessing the number of Respiratory tract infections recorded following IMP dosing between V2-V9

Full Information

NCT ID

NCT03084419

First Posted

March 7, 2017

Last Updated

July 18, 2019

Sponsor

Cambridge University Hospitals NHS Foundation Trust

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT03084419

Brief Title

APRIL (AbatacePt in Rheumatoid Arthritis-ILD)

Acronym

APRIL

Official Title

Safety of Abatacept in Rheumatoid Arthritis Associated Interstitial Lung Disease: A Feasibility Trial

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Unknown status

Study Start Date

June 26, 2018 (Actual)

Primary Completion Date

March 1, 2020 (Anticipated)

Study Completion Date

March 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cambridge University Hospitals NHS Foundation Trust

Collaborators

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis, Interstitial Lung Disease

Keywords

Rheumatoid Arthritis, Interstitial Lung Disease, RA-ILD, Abatacept

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

The investigators will perform a small clinical trial to assess the feasibility of performing a larger randomised controlled trial. 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. Participants will sign informed consent at visit 1 (screening visit). There is then a 28 day window before treatment starts at visit 2 (baseline). Each participants participation in the trial is estimated to last 28 weeks from visit 1.

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Abatacept in patients with RA-ILD

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Abatacept

Other Intervention Name(s)

Orencia

Intervention Description

The IV dose varies according to weight: <60kg=500mg ≥60 but≤100kg=750mg >100kg=1g This equates to approximately 10mg/kg.

Primary Outcome Measure Information:

Title

Forced Vital Capacity (FVC)

Description

Assessing the change of Forced Vital Capacity (FVC) across screening, baseline V2 (prior to abatacept), V6 and V9.

Time Frame

28 weeks (Screening-V9)

Secondary Outcome Measure Information:

Title

Transfer factor of the lung for carbon monoxide (TLCO)

Description

Assessing the change of Transfer factor of the lung for carbon monoxide (TLCO) at screening (prior to abatacept), V6 and V9.

Time Frame

28 weeks (Screening-V9)

Title

MRC dyspnoea score

Description

Assessing the change of MRC dyspnoea score completed at Baseline V2 (prior to abatacept), V6, V9

Time Frame

24 weeks (Baseline-V9)

Title

Kings Brief Interstitial Lung Disease score (K-BILD)

Description

Assessing the change of Kings Brief Interstitial Lung Disease score (K-BILD) questionnaire completed at Baseline V2 (prior to abatacept), V6, V9

Time Frame

24 weeks (Baseline-V9)

Title

Semi-quantitative radiological scoring of the ILD

Description

Assessing the change of HRCT chest scans performed at screening (prior to abatacept and V9 (end of trial)

Time Frame

28 weeks (Screening-V9)

Title

Resting oxygen saturation

Description

Resting oxygen saturation recorded at all visits

Time Frame

28 weeks

Title

DAS28

Description

DAS28 recorded at all visits

Time Frame

28 weeks

Title

Leicester Cough Questionnaire score

Description

Assessing the change of Leicester Cough Questionnaire completed at Baseline V2 (prior to abatacept), V6, V9

Time Frame

24 weeks (Baseline-V9)

Title

EQ-5D

Description

Assessing the change of EQ-5D Questionnaire completed at Baseline V2 (prior to abatacept), V6, V9

Time Frame

24 weeks (Baseline-V9)

Title

Respiratory tract infection

Description

Assessing the number of Respiratory tract infections recorded following IMP dosing between V2-V9

Time Frame

24 weeks (Baseline-V9)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Frances Hall

Phone

01223 274915

frances.hall@addenbrookes.nhs.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Elena Hernan-Sancho

elena.hernansancho@addenbrookes.nhs.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frances Hall

Organizational Affiliation

Addenbrookes Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Addenbrookes Hospital

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Frances Hall

Phone

01223 216182

ffrances.hall@addenbrookes.nhs.uk

First Name & Middle Initial & Last Name & Degree

Elena Hernan-Sancho

elena.hernansancho@addenbrookes.nhs.uk

First Name & Middle Initial & Last Name & Degree

Maeve Fifield

Facility Name

Papworth Hospital

City

Cambridge

ZIP/Postal Code

CB23 3RE

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Helen Parfrey

Phone

01480 830 541

hp226@cam.ac.uk

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

APRIL (AbatacePt in Rheumatoid Arthritis-ILD)

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