Clinical trial NCT04157010: Tocilizumab REMission in Early RA
Official title: Prospective, Single-centre, Open-Label, Randomised, Pilot Study Assessing the Changes in Expression of Janus Kinase/Signal Transducers and Activators of Transcription (JAK-STAT) and Speed & Depth of Remission Induced by Tocilizumab & Methotrexate Combination and Tocilizumab Monotherapy in Patients With Early Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2019-11-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The TREMERA study focuses on patients with newly diagnosed, untreated, rheumatoid arthritis (RA). Recent international treatment recommendations emphasise the need to diagnose RA early and start treatment immediately (this being associated with better response rates); and to aim for the goal of remission i.e. the absence of signs and symptoms of active inflammatory disease activity which is associated with better outcomes for the patient. Remission is more achievable with significant treatment advances that have been made in the form of highly effective biologic therapies. Tocilizumab (TCZ) is a newly introduced biologic drug that is used in established RA. The TREMERA study primarily aims to investigate the biological changes seen in blood and tissue following TCZ therapy this will contribute to a better understanding of how the drug works as well as disease processes; and will also identify whether administering a biologic drug such as TCZ can also switch off immunological parameters associated with a disrupted immune system of RA. The study will assess the effectiveness of TCZ given on its own or in combination with methotrexate (MTX; a standard therapy usually given with biologic treatments)in patients with early onset RA to determine the proportion that achieve remission. This study also aims to find out how quickly remission can be achieved with TCZ and the depth of remission achieved. This will be done using usual clinical assessment but also imaging such as ultrasound and magnetic resonance imaging (MRI) which can detect inflammation not apparent on clinical assessment.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of rheumatoid arthritis (2010 ACR/EULAR RA classification criteria)
* Symptom duration ≤12months
* No previous disease modifying antirheumatic drug (DMARD) therapy
* Active RA at baseline (defined as: DAS28 ≥ 3.2)
* Active hand and/or wrist joint evaluable by US and MRI (with no planned surgery during the study period)
* Patients without any contraindication to MRI

Exclusion Criteria:

* Patients unwilling or unable to receive MTX for the duration of the study.
* Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter's syndrome, psoriatic arthritis, systemic lupus erythematosis, or any arthritis with onset prior to 16 years of age.
* Suspicion of diagnosis of tuberculosis (TB): positive quantiferon +/abnormal chest x-ray, as per clinician judgement. Prior history of TB with confirmed full chemotherapy +/latent TB adequately treated may be included as per physician's discretion.
* Intramuscular, oral or intraarticular (of non-target joint) corticosteroid within 28 days of the screening visit; intra-articular steroid of the chosen target joint within 12 weeks of screening.
* Patients with serious infections within 3 month of enrolment (screening) or persistent infections.
* Patients at significant risk of infection (e.g. leg ulceration, indwelling urinary catheter, septic joint within 1 year (or ever if prosthetic joint still in situ).
* Known positive serology for hepatitis B or C, or HIV

Primary outcomes:
measure: Evaluate change in expression of JAK 1 and 3 (as well as STAT and p38 MAPK).
timeFrame: To week 60
Secondary outcomes:
measure: Reduction in inflammation in each treatment arm using ultrasound
timeFrame: To week 48
measure: Disease Activity Score (DAS): DAS28/44 remission
timeFrame: To week 48
measure: Questionnaires and research tools
timeFrame: Week 48
measure: Health Assessment Questionniaire (HAQ) scores
timeFrame: To week 48
measure: VAS scores questionnaire
timeFrame: To week 48
measure: Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire
timeFrame: To week 48
measure: Bone densitometry
timeFrame: Week 48.
measure: Sharp score on plain radiographs
timeFrame: Week 48.
Other outcomes:
measure: MRI sub-study (separately consented) - optional
timeFrame: To week 48
measure: Cardiovascular sub-study (separately consented) - optional
timeFrame: To week 48
Locations:
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
state: West Yorkshire
Study officials:
affiliation: University of Leeds
name: Dr Maya H Buch
role: PRINCIPAL_INVESTIGATOR
References: