Tocilizumab REMission in Early RA

Rheumatoid Arthritis Clinical Trial

— TREMERA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04157010
• Other study ID #: RR11/9965
• Secondary ID: 2011-004017-1714
• Status: Completed
• Phase: Phase 4
• Start date: May 2013
• Est. completion date: March 29, 2016

Study information

• Verified date: November 2019
• Source: University of Leeds
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 29, 2016
• Est. primary completion date: March 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tocilizumab

• Methotrexate

Locations

Country	Name	City	State
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	West Yorkshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Leeds	Hoffmann-La Roche

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	MRI sub-study (separately consented) - optional	Establish if reduction in RA MRI Scoring system (RAMRIS) synovitis score	To week 48
Other	Cardiovascular sub-study (separately consented) - optional	Change in cardiovascular measures on cardiac MRI and serum biomarkers	To week 48
Primary	Evaluate change in expression of JAK 1 and 3 (as well as STAT and p38 MAPK).	Changes up to week 60	To week 60
Secondary	Reduction in inflammation in each treatment arm using ultrasound	Establish reduction in inflammation in each treatment arm using ultrasound using grey scale power doppler	To week 48
Secondary	Disease Activity Score (DAS): DAS28/44 remission	Proportion of patients achieving DAS28/44 remission	To week 48
Secondary	Questionnaires and research tools	Using tools including DAS28/44, SDAI, CDAI	Week 48
Secondary	Health Assessment Questionniaire (HAQ) scores	The change from baseline in HAQ scores.	To week 48
Secondary	VAS scores questionnaire	The change in VAS scores for pain, disease activity	To week 48
Secondary	Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire	The change in RAQoL from baseline	To week 48
Secondary	Bone densitometry	Bone densitometry scan of hands, spine, femoral neck	Week 48.
Secondary	Sharp score on plain radiographs	Change in modified Sharp score on plain radiographs	Week 48.