Arthritis Prevention In the Pre-clinical Phase of Rheumatoid Arthritis with Abatacept
| ISRCTN | ISRCTN46017566 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN46017566 |
| EudraCT/CTIS number | 2013-003413-18 |
| Secondary identifying numbers | 16221 |
- Submission date
- 04/07/2014
- Registration date
- 04/07/2014
- Last edited
- 19/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
Rheumatoid arthritis (RA) is a common long-term inflammatory disease that causes pain, stiffness, swelling and limited motion of joints. RA can affect any joint (most commonly the small joints in the hands and feet) and can develop at any age. RA is thought to be an autoimmune disease, which means that something triggers the immune system to make an immune reaction (this includes the production of antibodies) that may cause damage to joint tissues. Over time, damage to the joint may lead to destruction of cartilage and bone. In some patients, the inflammation can affect other organs such as blood vessels, the eyes or lungs. If not well treated, the condition may lead to permanent damage to joints and disability, affecting quality of life. The purpose of this study is to find out whether RA can be prevented if treatment is given to people at high risk of developing the disease, as defined by the presence of autoantibodies in the blood, together with joint symptoms (pain but not joint swelling).
Who can participate?
Adults with joint pain and who have been found to have autoantibodies known to be associated with RA in their blood.
What does the study involve?
Participants will be randomly allocated to receive weekly injections of either abatacept (the drug licensed for use in established RA) or dummy (placebo) treatment over a 12-month period. This provides the best chance of establishing whether differences observed between the two groups are due to the treatment. The treatment will start at the first visit and participants will take weekly injections for 12 months and will be seen in the outpatient clinic every 3 months. Blood and urine tests will be done during these visits and some of the blood and urine will be used for routine monitoring of the effects of the study medication. Participants will also have an ultrasound scan of their joints at the first study visit and at 6, 12, 18 and 24 months, which may be performed on the same day. In addition to the three monthly visits, there will be brief telephone consultations to check that study subjects are administering their weekly injections, and to ask if there have been any changes in their symptoms. Once participants have completed the 12-month course of treatment, they will be seen in the outpatient clinic every 3 months to monitor the impact of the treatment. This follow-up period is especially important because if at any time participants develop new joint pains or swelling they will be assessed promptly and treated appropriately, in a similar way that clinical staff would assess any new patient presenting with arthritis.
What are the possible benefits and risks of participating?
Participants receiving drug treatment could experience some of the following side effects: throat or chest infections, headache, blood pressure increase, changes in liver function, loose stool, nausea, sore throat, fever, rashes, reduced white blood cell and tiredness and risk of injection site reactions in the skin. In general these are mild, and previous studies of abatacept have shown that the medication is well tolerated in patients with early as well as established RA. Nevertheless, for these reasons participants will be monitored closely through regular clinical assessments and blood testing so that any infections or side effects can be treated promptly.
Where is the study run from?
The study will be run from up to 30 study sites across the UK and the Netherlands.
When is study starting and how long is it expected to run for?
It is expected that recruitment will start in July 2014. Participants will be enrolled in the study for a period of 12 months of treatment with a further 12 months of follow up.
Who is funding the study?
Bristol-Myers Squibb (UK).
Who is the main contact?
Professor Andrew P. Cope (Chief Investigator), apippra@kcl.ac.uk
Contact information
Scientific
Centre for Rheumatic Diseases
1st Floor New Hunt’s House
Great Maze Pond
Guy’s Campus
King’s College London
London
SE1 1UL
United Kingdom
| apippra@kcl.ac.uk |
Public
APIPPRA Study Team
Clinical Trials Group
Centre for Rheumatic Diseases
School of Immunology and Microbial Sciences
Faculty of Life Sciences and Medicine
Weston Education Centre
King's College London
Cutcombe Road
Denmark Hill
London
SE5 9RJ
United Kingdom
| Phone | +44(0)20 7848 0852 |
|---|---|
| apippra@kcl.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Not specified |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet. |
| Scientific title | Arthritis Prevention In the Pre-clinical Phase of Rheumatoid Arthritis with Abatacept: a randomised controlled trial |
| Study acronym | APIPPRA |
| Study hypothesis | This study will test the hypothesis that the onset of arthritis in an 'at risk' group can be prevented or delayed by weekly injections of abatacept for a period of 12 months. The specific aims of this study are to: 1. Evaluate the feasibility, efficacy and acceptability of abatacept therapy in subjects at high risk of developing RA, and 2. Characterise immune and inflammatory responses associated with ACPA before, during and after therapy with abatacept. On 13/01/2015 the following changes were made to the trial record: 1. Netherlands was added to the countries of recruitment (target number of participants: 20). 2. The overall trial start date was changed from 01/08/2014 to 12/12/2014. 3. The overall trial end date was changed from 31/07/2016 to 11/12/2018. 4. King’s College London was added as a sponsor. |
| Ethics approval(s) | 14/LO/0100; First MREC approval date 13/03/2014 |
| Condition | Topic: Musculoskeletal disorders; Subtopic: Musculoskeletal (all Subtopics); Disease: Musculoskeletal |
| Intervention | Participants will be randomised into one of two arms: 1. Abatacept 2. Matching placebo Participants will receive weekly injections of 125 mg/ml of abatacept or placebo, starting from baseline (week 0) for a period of 52 weeks. They will be trained to self-administer the study drug subcutaneously using the single-dose prefilled syringe according to local practices for the administration of biological therapy as part of standard care. They will be followed up for an additional period of 52 weeks. Participants will be seen at 3 monthly intervals throughout the duration of the study. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Abatacept |
| Primary outcome measure | Time to development of clinical synovitis or RA |
| Secondary outcome measures | The development of RA according to the ACR/EULAR 2010 criteria |
| Overall study start date | 12/12/2014 |
| Overall study end date | 13/01/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 206; UK Sample Size: 186; Netherlands: 20 |
| Total final enrolment | 213 |
| Participant inclusion criteria | 1. Male or female subjects, aged 18 years or over 2. Arthralgia, defined as non-traumatic joint pain localised to synovial joints including, but not necessarily confined to, hands, wrists or feet, and in the opinion of the supervising rheumatologist considered to be inflammatory in nature 3. Positive for serum rheumatoid factor (RF) and antibodies to citrullinated protein antigens (ACPA) as defined by local clinical laboratory testing. Subjects who are RF negative, but who carry high levels of serum ACPA (defined as being = 3 x upper limit of normal [ULN] for the assay) may be included 4. Able and willing to give written informed consent and comply with the requirements of the study protocol |
| Participant exclusion criteria | 1. Previous diagnosis of RA or other form of inflammatory arthritis including, but not limited to, SLE, psoriatic arthritis, ankylosing spondylitis, gout or pyrophosphate arthopathy, and including current treatment with DMARDs or biological therapy 2. Arthralgia that, in the opinion of the supervising physician, is poorly localised, e.g., pelvic or shoulder girdle pain that is confined to the axial skeleton or entheses, or pain which the physician considers to be due to osteoarthritis or fibromyalgia, or related to other autoimmune conditions such as type I diabetes, coeliac or autoimmune thyroid disease 3. Clinically apparent arthritis, as assessed by a rheumatologist, characterised by soft tissue swelling of one or more synovial joints. Subclinical synovitis, as detected by imaging modalities such as ultrasonography or MRI, is NOT an exclusion criterion 4. A history of oral or parenteral use of corticosteroids within the last 12 weeks used to treat the current episode of musculoskeletal symptoms 5. Co-morbidities requiring chronic treatment with immunosuppressive or immune-modulating therapy 6. Subjects who have at any time received treatment with any investigational drug within 28 days 7. A history of acute allergic reactions to biological therapy or immunoglobulins 8. Subjects who are incapable of completing study-related assessments or give informed consent 9. Subjects with current symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic or cerebral disease, whether or not related to RA and which, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study 10. Subjects with a cancer history within the last 5 years 11. Subjects with tuberculosis (including those at high risk of tuberculosis), chronic viral infections, recent serious bacterial infections, or subjects receiving live vaccinations within 3 months of the anticipated first dose of study medication, or those with chronic illnesses that would, in the opinion of the investigator, put the patient at risk 12. Subjects who currently abuse drugs or alcohol 13. Subjects who are pregnant or who are breastfeeding 14. Male subjects or women of childbearing potential not willing to use adequate contraception during the period of IMP dosing and for up to 10 weeks after the last dose of study drug 15. Subjects with abnormal laboratory tests, as defined in the study protocol |
| Recruitment start date | 01/08/2014 |
| Recruitment end date | 14/01/2019 |
Locations
Countries of recruitment
- England
- Netherlands
- United Kingdom
Study participating centre
SE1 1UL
United Kingdom
Sponsor information
Hospital/treatment centre
Evelina Children's Hospital
Lambeth Palace Road
London
SE1 7EH
England
United Kingdom
| crf@gstt.nhs.uk | |
| Website | http://www.guysandstthomas.nhs.uk/Home.aspx |
"ROR" |
https://ror.org/00j161312 |
University/education
Strand
London
WC2R 2LS
England
United Kingdom
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Bristol-Myers Squibb Company, BMS
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/07/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available. Informed consent for sharing individual de-identified participant data was not obtained from the study participants. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 15/07/2019 | 05/06/2020 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 13/02/2024 | 19/02/2024 | Yes | No |
Editorial Notes
19/02/2024: Publication reference added.
04/04/2023: The study contact confirmed that as of this date the study record is correct.
19/07/2022: The intention to publish date has been changed from 31/07/2022 to 31/07/2023.
24/01/2022: The intention to publish date has been changed from 13/01/2022 to 31/07/2022.
28/07/2021: IPD sharing statement added.
20/07/2021: The following changes have been made:
1. The recruitment end date was changed from 31/07/2016 to 14/01/2019.
2. The overall trial end date was changed from 31/07/2021 to 13/01/2021.
3. The intention to publish date was changed from 31/07/2021 to 13/01/2022.
4. The total final enrolment number was added.
05/06/2020: The following changes have been made:
1. The scientific contact has been changed and a public contact added.
2. The plain English summary has been updated to reflect the change in contact details.
3. The EudraCT number has been added.
4. Publication reference added.
5. The intention to publish date has been added.
06/12/2019: The overall trial end date has been changed from 11/12/2018 to 31/07/2021.
