APRIL (AbatacePt in Rheumatoid Arthritis-ILD)

NCT03084419 | Unknown Phase 2 DMC

• 1 other identifier: APRIL
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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).

Conditions

Rheumatoid Arthritis; Interstitial Lung Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Forced Vital Capacity (FVC)

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

  28 weeks (Screening-V9)

Secondary Outcomes (9)

• Transfer factor of the lung for carbon monoxide (TLCO)

  28 weeks (Screening-V9)

• 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)

• Resting oxygen saturation

  28 weeks

Study Arms (1)

Abatacept in patients with RA-ILD

EXPERIMENTAL

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.

Drug: Abatacept

Interventions

Abatacept DRUG

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

Also known as: Orencia

Abatacept in patients with RA-ILD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Unable to provide informed written consent
• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Papworth Hospital

Cambridge, CB23 3RE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid; Lung Diseases, Interstitial

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Frances Hall

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frances Hall

CONTACT

01223 274915; frances.hall@addenbrookes.nhs.uk

Elena Hernan-Sancho

CONTACT

elena.hernansancho@addenbrookes.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Rheumatologistand and Clinical Lead for Connective Tissue Disease

Model Details: 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.

Study Record Dates

• First Submitted: March 7, 2017
• First Posted: March 21, 2017
• Study Start: June 26, 2018
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: July 22, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)