The 3TR Molecular Pathobiology-Driven Precision Therapy in RA (3TR Precis-The-RA) study

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

12 Oct 2023 → ongoing

Decision date (initial)

2023-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Innovative Medicines Initiative 2 Joint Undertaking IMI2 JU

External identifiers

EU CT number

2022-502021-18-00

ISRCTN

ISRCTN44988547

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

This study will test the utility of synovial tissue biomarkers (=drug target signatures) to enrich for treatment response in RA patients failing csDMARD therapy and starting on a biologic therapy (e.g. anti-TNF, IL6 inhibitor). The specific aim of the sub-study is to discover if a biopsy at presentation prior to any RA treatment (collected as part of the 3TR-PARTNER-RA study) can be used to determine treatment response even after the patient has received cDMARDs.

Secondary objectives 3

1. Firstly, we will compare patients treated according to their biomarker in the intervention arm against the control arm as a whole (i.e. Group 1 vs 3+4), to determine the enrichment in response in the treatment allocation arm vs the standard of care response rate.
2. Secondly, to assess the efficacy of treatment allocation according to biomarker compared to random allocation, we will compare the biomarker positive patients in the intervention arm vs the biomarker positive patients in the control arm (i.e. Group 1 vs Group 4)
3. Finally, we aim to assess the efficacy of the strategy as a whole against the current clinical practice by comparing the control vs intervention arm (i.e. Groups 1 + 2 vs Group 3+4)

Conditions and MedDRA coding

Rheumatoid Arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 2010 ACR / EULAR classification criteria for a diagnosis of Rheumatoid Arthritis
2. Patients with csDMARD failure and eligible for anti-TNF therapy according to EULAR recommendations: treatment for ≥3months with ≥ 1 csDMARDs
3. Patients must have a DAS>5.1 and a minimum of 3 swollen joints – where the patient is undergoing a biopsy at visit 2, these should include the joint selected for biopsy and 2 other joints, as assessed at biopsy visit
4. Selected joint for biopsy must be minimum grade 2 synovial thickening, as assessed at the biopsy visit
5. 18 years of age or over
6. Patients must be capable of giving informed consent and the consent must be obtained prior to any screening procedures
7. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures

Exclusion criteria 27

1. Women who are pregnant or breast-feeding
2. 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
3. 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)
4. Prior exposure to any biologic/targeted DMARDs for 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. Intra-articular or parenteral corticosteroids ≤ 4 weeks prior to screening visit
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 or in line with clinical practice
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
14. New York Heart Association (NYHA) grade III or IV congestive heart failure
15. Demyelinating disease
16. Known allergy to latex, or known hypersensitivity to the study medication active substance or to any of the excipients of the IMP
17. Any other contra-indication to the study medications as detailed in the applicable SmPC
18. Receipt of live vaccine <4 weeks prior to first dose of study medication
19. Major surgery in 3 months prior to first dose of study medication
20. Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening)
21. Known recent substance abuse (drug or alcohol)
22. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period
23. 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
24. Patients currently recruited to other clinical trials
25. 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
26. Patients with severe hepatic impairment (Child Pugh C classification)
27. Patients that are immunocompromised

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study will be a binary outcome of treatment responder/nonresponder classified using American College of Rheumatology 50 (ACR-50) measure at 12 weeks.

Secondary endpoints 5

1. Percentage of patients with DAS28(ESR)<3.2 (LDA) at 12 weeks
2. Percentage of patients with CDAI ≤10 (LDA) at 12 weeks
3. Percentage of patients with CDAI remission at 12 weeks
4. Change in HAQ-DI at 12 weeks from baseline
5. Change in SF-36 at 12 weeks from baseline

Investigational products

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

Test 3

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

Joanna Peel

Public contact point

Organisation

Queen Mary University Of London

Contact name

Joanna Peel

Locations

5 EU/EEA countries · 12 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 117 files

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

Application history

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