3TR-PARTNER-RA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Queen Mary University Of London

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

11 Feb 2025 → ongoing

Decision date (initial)

2025-02-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Innovative Medicines Initiative 2 Joint Undertaking IMI2 JU

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To determine whether synovial molecular profiles, specifically the presence of CD80/CD86 biomarkers, can predict the clinical response to abatacept treatment in patients with early rheumatoid arthritis (RA).

Secondary objectives 1

1. We aim to assess patients treated according to their biomarker: comparing the biomarker- positive patients (as Groups 1 minus 2) vs the biomarker-negative patients (as Groups 3 minus 4).

Conditions and MedDRA coding

Rheumatoid Arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adults (female and male) aged 18 or over.
2. Willing and capable of giving informed consent
3. 2010 ACR / EULAR classification criteria for a diagnosis of Rheumatoid Arthritis* (* The ACR/EULAR classification for a diagnosis of RA could have been at any time in the patient’s disease history; the score does not need to be 6 or more at screening.)
4. Symptom duration of <12 months
5. At least one swollen joint, which is amenable to synovial biopsy (minimum grade 2 synovial thickening, as assessed at the biopsy visit)
6. Moderate and severe Disease Activity (DAS28>3.2)
7. No prior DMARD therapies (conventional, targeted or biologic DMARDs)
8. Patient is judged by the supervising clinician to be a suitable candidate based upon medical history, physical examination, vital signs, and routine laboratory tests.
9. Willing and able to comply with scheduled visits, laboratory tests, and other study procedures.

Exclusion criteria 26

1. Patients unable to tolerate synovial biopsy or in whom this is contraindicated including patients on anti-coagulants (e.g. warfarin). Patients on short-acting direct oral anticoagulant agents can be considered when anti-coagulant can be temporarily stopped, in line with local guidelines for procedures with a low risk of bleeding, taking into account the individual thromboembolic risk. Oral anti-platelet agents are permitted.
2. Patients in whom there is no suitable joint for biopsy
3. Hypersensitivity to the active substance or to any of the excipients of abatacept or methotrexate, or any other contraindications to the study medications, as per the current SmPC
4. History of or current primary inflammatory joint disease or primary rheumatological autoimmune disease other than RA (if secondary to RA, then the patient is still eligible)
5. Prior exposure to any conventional/biologic/targeted DMARDs for RA
6. Treatment with any investigational agent ≤ 8 weeks prior to baseline or < 5 half-lives of the investigational drug (whichever is the longer)
7. Intra-articular or parenteral corticosteroids, or oral prednisolone more than 10mg/d or equivalent ≤ 4 weeks prior to screening visit
8. Patients with a serious underlying medical disorder (e.g., end stage renal disease).
9. Active infection
10. Subject has a history or known presence of recurrent or chronic infection (eg, hepatitis B virus [HBV], hepatitis C virus [HCV], human immunodeficiency virus HIV]; recurrent urinary tract infections are allowed.
11. Subjects testing positive for acute or chronic hepatitis A, B, or C, unless they are indicative of prior hepatitis B vaccination or cured hepatitis A or B and accompanied by normal liver transaminase values.
12. Septic arthritis of a native joint within the last 12 months
13. Septic arthritis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ
14. Latent TB infection unless they have completed adequate antibiotic prophylaxis
15. Receipt of live vaccine <3 months prior to first dose of study medication
16. Major surgery in 3 months prior to first dose of study medication
17. Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening).
18. Known recent substance abuse (drug or alcohol).
19. Patients currently recruited to other clinical trials or taking part in a CTIMP study in the previous 4 months.
20. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. This should include assessment of risk factors for known clinically important risks associated with a study drug.
21. Patients with severe hepatic impairment (Child Pugh C classification).
22. Patients that are primary or secondary immunodeficiency (history of or currently active).
23. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period.
24. Women who are pregnant or breast-feeding.
25. Women of child-bearing potential or males whose partners are women of child-bearing potential, unwilling to use an effective method of contraception (recommend double contraception) throughout the trial and beyond the end of trial treatment for the duration as defined in the relevant SmPC
26. Individuals who are unable to give informed consent for any reason (vulnerable groups).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study will be the delta CDAI at 16 weeks

Secondary endpoints 5

1. Percentage of patients with DAS28<3.2 (LDA) at 16 weeks.
2. Percentage of patients deemed responders using American College of Rheumatology 50 (ACR50) measure at 16 weeks.
3. Percentage of patients with CDAI remission at 16 weeks
4. Change in HAQ-DI at 16 weeks from baseline.
5. Change in SF-36 at 16 weeks from baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Queen Mary University Of London

Sponsor organisation

Queen Mary University Of London

Address

Charterhouse Square

City

London

Postcode

EC1M 6BQ

Country

United Kingdom

Scientific contact point

Organisation

Queen Mary University Of London

Contact name

The EMR Clinical Trials Unit

Public contact point

Organisation

Queen Mary University Of London

Contact name

The EMR Clinical Trials Unit

Locations

5 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 111 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications