Tocilizumab REMission in Early RA

NCT04157010 | Completed Phase 4 DMC

• 3 other identifiers: RR11/99652011-004017-1714383
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Reduction in inflammation in each treatment arm using ultrasound

  To week 48

• Disease Activity Score (DAS): DAS28/44 remission

  To week 48

• Questionnaires and research tools

  Week 48

• Health Assessment Questionniaire (HAQ) scores

  To week 48

• VAS scores questionnaire

  To week 48

Other Outcomes (2)

• MRI sub-study (separately consented) - optional

  To week 48

• Cardiovascular sub-study (separately consented) - optional

  To week 48

Study Arms (2)

TCZ monotherapy

EXPERIMENTAL

Tocilizumab (TCZ) monotherapy 8mg/kg 4-weekly for a total of 48 weeks.

Drug: Tocilizumab

TCZ+MTX combination therapy

EXPERIMENTAL

Tocilizumab (TCZ) and methotrexate (MTX) combination therapy 8mg/kg 4-weekly for a total of 48 weeks.

Drug: Tocilizumab; Drug: Methotrexate

Interventions

Tocilizumab DRUG

TCZ monotherapy; TCZ+MTX combination therapy

Methotrexate DRUG

TCZ+MTX combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Leeds: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS7 4SA, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Dr Maya H Buch

  University of Leeds

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: November 8, 2019
• Study Start: May 1, 2013
• Primary Completion: March 29, 2016
• Study Completion: March 29, 2016
• Last Updated: November 8, 2019

Record last verified: 2019-11

Locations

GB (1)