Ultrasound as Imaging Biomarker of Early Response to Tocilizumab and Methotrexate in Very Early Rheumatoid Arthritis

NCT02837146 | Unknown Phase 3 DMC

• 2 other identifiers: P1200_142015-001246-28
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study is aimed at assessing the kinetics of the ultrasound (US) response in DMARD-naive very early rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ) and methotrexate (MTX).

Conditions

Rheumatoid Arthritis

Keywords

RA

Outcome Measures

Primary Outcomes (2)

• Change in global ultrasound scoring system (GLOSS) at MCP (2-5 joints of both hands) and wrist joints

  MCP=metacarpophalangeal; GLOSS scoring according to OMERACT: Grade 0 or normal=normal joint (no synovial hypertrophy (SH), no Doppler signal); Grade1 or minimal=minimal synovitis (minimal SH, with ≤ grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate SH, with ≤ grade 2 Doppler signal or minimal SH and grade 2 Doppler signal); Grade 3 or severe=severe synovitis (severe SH with ≤ grade 3 Doppler signal or minimal or moderate SH and grade 3 Doppler signal). Joints are scored 0 to 3, and the sum of individual joints scores represents the total GLOSS for a subject.

  Baseline to weeks 2, 4, 8, 12, 16, 24, 32, 40, 54

• The earliest time point at which improvement in GLOSS at MCP (2-5 joints of both hands) and wrists can be detected

  Baseline to weeks 2, 4, 8, 12, 16, 24, 32, 40, 54

Secondary Outcomes (22)

• GLOSS measured at 8 and 12 weeks is predictive to later clinical response at 24 and at 48 weeks

  weeks 12, 24, 48

• Minimum set of joints to be monitored by US in order to adequately assess disease activity

  Baseline to weeks 2, 4, 8, 12, 16, 24, 32, 40, 54

• Change in GLOSS for the whole US joint set

  Baseline to weeks 2, 4, 8, 12, 16, 24, 32, 40, 54

• Change in power Doppler (PD) scores for the whole US joint set

  Baseline to weeks 2, 4, 8, 12, 16, 24, 32, 40, 54

• Change in gray-scale (GS) scores for the whole US joint set

  Baseline to weeks 2, 4, 8, 12, 16, 24, 32, 40, 54

Study Arms (1)

Tocilizumab (TCZ) + Methotrexate (MTX)

EXPERIMENTAL

Induction phase: From week 0 to week 24, all subjects will receive TCZ and MTX Maintenance phase: From week 24 to week 54, all subjects will receive MTX

Biological: Tocilizumab (TCZ); Drug: Methotrexate (MTX)

Interventions

Tocilizumab (TCZ) BIOLOGICAL

Induction phase: TCZ subcutaneously (162 mg weekly) from baseline to week 24

Also known as: Ro-Actemra

Tocilizumab (TCZ) + Methotrexate (MTX)

Methotrexate (MTX) DRUG

Induction and maintenance phase: Methotrexate 15-20 mg/week from baseline to week 54

Also known as: Ledertrexate, Emthexate

Tocilizumab (TCZ) + Methotrexate (MTX)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of RA fulfilling the 2010 EULAR/ACR (European League Against Rheumatism/ American College of Rheumatology classification criteria)
• Disease duration no longer than 12 months from the time of first swollen joint and no longer than 12 months from the time of initial diagnosis
• Age : 18-75 years
• Disease activity defined by a disease activity score DAS28-CRP \> 3.2 or all must be met: tender joint count (TJC) of ≥4 and swollen joint count (SJC) ≥4
• US SH or PD synovitis scores \>1 for at least 2 joints (MCP:2-5 or PIP:2-5 or CMC:2-5 or wrist joints or MTP:2-5 or ankle joints) and US SH or PD synovitis scores ≥1 for at least 1 other joint (MCP:2-5 or PIP:2-5 or or CMC:2-5 or wrist joints)
• Naïve to DMARDs (methotrexate, leflunomide, sulphasalazine) and naïve to any biologics or biosimilars.

You may not qualify if:

• History of other concomitant autoimmune disease such as lupus or psoriatic arthritis
• Meeting diagnostic criteria for any other rheumatic disease than RA (e.g. gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic arthritis, arthropathy or inflammatory bowel disease)
• Any previous treatment with :
• Biologics: Etanercept, infliximab, certolizumab, golimumab, abatacept, adalimumab, anakinra, tocilizumab, tofacitinib, etc.
• Any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti- CD3, anti-CD19 and anti-CD20
• Intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
• Alkylating agents such as chlorambucil, or with total lymphoid irradiation
• Previous MCP arthroplasty or wrist arthrodesis. Participants who have undergone or are scheduled to undergo joint arthroplasties other than the MCP joints can be recruited in the study provided all other eligibility criteria are met.
• Current liver disease requiring medication
• History of malignancy or lymphoproliferative disease, within the last 5 years, with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of cervix which that has been fully excised/cured with no evidence of recurrence
• Concomitant diagnosis or history of diverticulitis, peptic ulcer disease, diverticulosis requiring antibiotic treatment or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations
• Evidence of active or latent bacterial, viral, fungal (except for fungal infections of nail beds), mycobacterial or other opportunistic infections at the time of potential enrolment
• Any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 4 weeks or oral antibiotics within 2 weeks of screening'
• Herpes zoster or cytomegalovirus infection that resolved less than 2 months before the informed consent was signed
• Subjects at risk of tuberculosis (TB) are excluded if any of the following is present:

Sponsors & Collaborators

• Maria Stoenoiu: lead

Study Sites (1)

Maria S Stoenoiu

Brussels, Belgium, 1200, Belgium

RECRUITING

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

• Maria S Stoenoiu, MD, PhD

  Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria S Stoenoiu, MD, PhD

CONTACT

+32 2 7645391; maria.stoenoiu@uclouvain.be

M'Zoughui Marie

CONTACT

+32 2 764 5390; marie.mzoughui@uclouvain.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: July 7, 2016
• First Posted: July 19, 2016
• Study Start: December 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: July 29, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)