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Tocilizumab REMission in Early RA (TREMERA)

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ClinicalTrials.gov Identifier: NCT04157010
Recruitment Status : Completed
First Posted : November 8, 2019
Last Update Posted : November 8, 2019
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Dr Maya Buch, University of Leeds

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Tocilizumab Drug: Methotrexate Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2013
Actual Primary Completion Date : March 29, 2016
Actual Study Completion Date : March 29, 2016

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Arm Intervention/treatment
Experimental: TCZ monotherapy
Tocilizumab (TCZ) monotherapy 8mg/kg 4-weekly for a total of 48 weeks.
Drug: Tocilizumab
Experimental: TCZ+MTX combination therapy
Tocilizumab (TCZ) and methotrexate (MTX) combination therapy 8mg/kg 4-weekly for a total of 48 weeks.
Drug: Tocilizumab
Drug: Methotrexate



Primary Outcome Measures :
  1. Evaluate change in expression of JAK 1 and 3 (as well as STAT and p38 MAPK). [ Time Frame: To week 60 ]
    Changes up to week 60


Secondary Outcome Measures :
  1. Reduction in inflammation in each treatment arm using ultrasound [ Time Frame: To week 48 ]
    Establish reduction in inflammation in each treatment arm using ultrasound using grey scale power doppler

  2. Disease Activity Score (DAS): DAS28/44 remission [ Time Frame: To week 48 ]
    Proportion of patients achieving DAS28/44 remission

  3. Questionnaires and research tools [ Time Frame: Week 48 ]
    Using tools including DAS28/44, SDAI, CDAI

  4. Health Assessment Questionniaire (HAQ) scores [ Time Frame: To week 48 ]
    The change from baseline in HAQ scores.

  5. VAS scores questionnaire [ Time Frame: To week 48 ]
    The change in VAS scores for pain, disease activity

  6. Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire [ Time Frame: To week 48 ]
    The change in RAQoL from baseline

  7. Bone densitometry [ Time Frame: Week 48. ]
    Bone densitometry scan of hands, spine, femoral neck

  8. Sharp score on plain radiographs [ Time Frame: Week 48. ]
    Change in modified Sharp score on plain radiographs


Other Outcome Measures:
  1. MRI sub-study (separately consented) - optional [ Time Frame: To week 48 ]
    Establish if reduction in RA MRI Scoring system (RAMRIS) synovitis score

  2. Cardiovascular sub-study (separately consented) - optional [ Time Frame: To week 48 ]
    Change in cardiovascular measures on cardiac MRI and serum biomarkers



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04157010


Locations
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United Kingdom
Leeds Teaching Hospitals NHS Trust
Leeds, West Yorkshire, United Kingdom, LS7 4SA
Sponsors and Collaborators
University of Leeds
Hoffmann-La Roche
Investigators
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Principal Investigator: Dr Maya H Buch University of Leeds

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Responsible Party: Dr Maya Buch, Chief Investigator, University of Leeds
ClinicalTrials.gov Identifier: NCT04157010     History of Changes
Other Study ID Numbers: RR11/9965
2011-004017-17 ( EudraCT Number )
14383 ( Other Identifier: UKCRN )
First Posted: November 8, 2019    Key Record Dates
Last Update Posted: November 8, 2019
Last Verified: November 2019
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors