ltrasound scores as imaging biomarkers of early response to subcutaneous tocilizumab in association with methotrexate in early rheumatoid arthritis (TOVERA study)

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 18.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2015-001246-28-BE
• Lead Sponsor: Cliniques Universitaires Saint-Luc, Université catholique de Louvain

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-23
• Last Update Posted: 23 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Inclusion criteria
1.Diagnosis of RA fulfilling the 2010 EULAR/ACR (European League Against Rheumatism/ American College of Rheumatology classification criteria)
2.Disease duration no longer than 12 months from the time of initial diagnosis
3.Age : 18-70 years
4.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
5.US SH or PD synovitis scores >1 for at least 2 metacarpophalangeal (MCP) joints (2-5) and US SH or PD synovitis scores =1
6.Naïve to DMARD (methotrexate, leflunomide, sulphasalazine) and biologics (TNF-, IL6-, CD20-, IL1-blockers)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Exclusion criteria
1.History of other concomitant autoimmune disease such as lupus or psoriatic arthritis
2.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)
3.Any previous treatment with :
a.Etanercept, infliximab, certolizumab, golimumab, abatacept or adalimumab, anakinra
b.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
c.Intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
d.Alkylating agents such as chlorambucil, or with total lymphoid irradiation
4.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.
5.Current liver disease requiring medication
6.Current symptoms of severe progressive or uncontrolled renal, hematologic, gastro-intestinal, pulmonary, cardiac, neurologic or cerebral disease whether or not related to rheumatoid arthritis, that would jeopardize inclusion in the protocol as judged by the clinician
7.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
8.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
9.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
10.Any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 4 weeks or oral antibiotics within 2 weeks of screening’
11.Herpes zoster or cytomegalovirus infection that resolved less than 2 months before the informed consent was signed
12.Subjects at risk of tuberculosis (TB) are excluded if any of the following is present:
-A history of active TB within the last 3 years, even if treated
-Latent TB that was not successfully treated = 4 weeks
-Current clinical radiographic, or laboratory evidence of active TB
13.Subjects who received live vaccines within 4 weeks of the anticipated first dose of study medication. Live and live attenuated vaccines should not be given concurrently
14.Subjects must agree not to take live attenuated vaccines (including seasonal nasal flu vaccine, varicella vaccine for shingles or chickenpox, MMR or MMRV, oral polio vaccine and vaccines for yellow fever, measles, mumps or rubella) thirty (30) days before the Screening Visit, throughout the duration of the trial and for sixty (60) days following the subject’s last dose of study drug
15.Subjects with positive test results for hepatitis B surface antigen or hepatitis C, or HIV detected with polymerase chain reaction or immunoblot assay
16.Subjects with primary or secondary immunodeficiency
17.History of severe allergic or anaphylactic reactions to human

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified