Condition category
Musculoskeletal Diseases
Date applied
05/11/2015
Date assigned
05/11/2015
Last edited
15/03/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Rheumatoid arthritis (RA) is a long-term disease causing pain, swelling (inflammation) and stiffness in the joints. It is part of a group of diseases called autoimmune diseases, where the immune system starts to attack healthy joints. In healthy people, the body produces different types of immune cells. One of these is the B-cell, which produces antibodies to fight infection. In people with RA, these do not behave properly and produce antibodies which attack a person’s own body even if there is no infection. There are 26,000 new cases of RA each year, which costs the NHS around £560 million annually. Often the first line of treatment involves the use of disease-modifying anti-rheumatic drugs (DMARDs), which work by slowing down the progress of the disease by suppressing the immune system. In about 40% of cases however, patients do not show any real signs of improvement (DMARD failures). In recent years, drug treatments for RA have improved dramatically. So-called “biologic treatments” such as the drug tocilizumab, are made from proteins and work by blocking the activity of the chemicals or cells which trigger the inflammation of the joints. Another important treatment used in RA is a group of drugs known as anti-TNF (anti-tumour necrosis factor), such as etanercept and rituximab, which work directly on the immune system to reduce the number of B-cells, stopping them from producing antibodies which will attack the healthy cells. Currently patients are treated with tocilizumab, etanercept or rituximab on a trial and error basis. The aim of this study is to predict which treatment will work best for patients, this is known as stratified or personalised medicines.

Who can participate?
Adults with RA who have DMARD failure and are eligible for antiTNFa therapy.

What does the study involve?
Participants are randomly allocated to one of three groups, who are each treated with a different drug. Those in the first group receive a 50mg subcutaneous injection (injection under the skin) of etanercept once a week. Those in the second group receive a 1000mg intravenous infusion (a drip into a vein) of rituximab day 1 and 15 of the study this treatment is repeated every 24 weeks. Those in the third group receive a 162mg subcutaneous injection of tocilizumab once a week. The number of participants in each treatment group who show more than a 20% improvement (ARC20) in their symptoms are counted 16 weeks into the study.

What are the possible benefits and risks of participating?
Benefits include regular reviews and if treatment is not effective it will be switched at 4months rather than at 6 months. There is a small risk of complications associated with the biopsy and patients receiving Rituximab as part of the trial might not be guaranteed to continue to receive it. This is because treatment with Rituximab typically requires you to have been treated with another biological drug first in standard care.

Where is the study run from?
Centre for Experimental Cancer Medicine, Barts and the London School of Medicine (UK)

When is the study starting and how long is it expected to run for?
June 2015 to June 2018

Who is funding the study?
Medical Research Council (UK)

Who is the main contact?
Miss Laura White

Trial website

http://www.matura-mrc.whri.qmul.ac.uk

Contact information

Type

Public

Primary contact

Miss Laura White

ORCID ID

Contact details

Centre for Experimental Cancer Medicine
LG floor
Old Anatomy Building
Charterhouse Square
London
EC1M 6BQ
United Kingdom

Additional identifiers

EudraCT number

2014-003529-16

ClinicalTrials.gov number

Protocol/serial number

18178

Study information

Scientific title

Stratification of Biologic Therapies for Rheumatoid Arthritis by Pathobiology (STRAP): A randomised, open-labelled biopsy driven stratification trial in DMARD inadequate responder patients randomised to etanercept, tocilizumab or rituximab

Acronym

STRAP

Study hypothesis

In patients failing DMARD therapy, with a B cell poor synovial pathotype, Rituximab is inferior to Tocilizumab and Etanercept therapy.

Ethics approval

Wales Research Ethics Committee, 16/12/2014, ref: 314/WA/1209

Study design

Three-arm randomised parallel trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Musculoskeletal disorders; Subtopic: Musculoskeletal (all Subtopics); Disease: Musculoskeletal

Intervention

Participants are randomly allocated to one of three groups:

Group 1: Participants receive 50mg etanercept administered subcutaneously once weekly for the study duration.
Group 2: Participants receive 1000mg rituximab by iv infusion on days 1 and 15. This cycle is repeated every 24 weeks.
Group 3: Participants receive 162 mg tocilizumab administered subcutaneously once weekly for the study duration.

Intervention type

Drug

Phase

Not Applicable

Drug names

1. Etanercept
2. Rituximab
3. Tocilizumab

Primary outcome measures

Treatment efficacy is determined by calculating the number of patients with an ACR 20 response at 16 weeks.

Secondary outcome measures

Not provided at time of registration

Overall trial start date

15/06/2015

Overall trial end date

15/06/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. 2010 ACR / EULAR Rheumatoid Arthritis classification criteria for a diagnosis of RA
2. Patient with DMARD failure eligible for antiTNFa therapy as per UK NICE guidelines (those who have both of the following):
2.1. Active RA as measured by DAS28>5.1
2.2. Have undergone trials of two DMARDs, including MTX (unless contraindicated). A trial of a DMARD is defined as being normally of 6 months, with 2 months at standard dose, unless significant toxicity has limited the dose or duration of treatment.
3. Over 18 years of age
4. Patients must be capable of giving informed consent and the consent must be obtained prior to any screening procedures

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 207; UK Sample Size: 207

Participant exclusion criteria

1. Women who are pregnant or breastfeeding
2. Women of childbearing potential or males whose partners are women of childbearing potential, unwilling to use effective contraception during the study (recommend double contraception) throughout the trial and beyond the end of trial treatment for the duration as defined in the relevant SmPC; 12 months for Rituximab, at least 3 weeks for Etanercept, and at least 3 months for Tocilizumab
3. History of or current inflammatory joint disease or autoimmune disease other than RA (if secondary to RA, then the patient is still eligible)
4. Prior exposure to Rituximab, any antiTNF, Tocilizumab, or any biologic for treatment of RA
5. Treatment with any investigational agent ≤ 4 weeks prior to baseline or < 5 half-lives of the investigational drug (whichever is the longer)
6. Intraarticular or parenteral corticosteroids ≤ 4 weeks prior to baseline synovial biopsy
7. Oral prednisolone more than 10mg/d or equivalent ≤ 4 weeks prior to baseline synovial biopsy
8. Active infection
9. Known HIV, active Hepatitis B/C infection. Hepatitis B screening test must be performed at or in the preceding 3 months of screening visit
10. Septic arthritis of a native joint within the last 12 months
11. Septic arthritis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ
12. Latent TB infection unless they have completed adequate antibiotic prophylaxis
13. Malignancy (other than basal cell carcinoma) within the last 10 years

Recruitment start date

15/06/2015

Recruitment end date

15/06/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Centre for Experimental Cancer Medicine
Barts and the London School of Medicine LG floor Old Anatomy Building Charterhouse Square
London
EC1M 6BQ
United Kingdom

Sponsor information

Organisation

Barts Health NHS Trust

Sponsor details

Peri-operative medicine research group
Adult Critical Care Research Office
Level 4
The Royal London Hospital
London
E1 1BB
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

15/03/2016: Verified study information with principal investigator.