rheumatoid arthritis (RA)
Conditions
Interventions
Trade Name: OLUMIANT 4mg
Pharmaceutical Form: Cachet
Trade Name: IMRALDI 40mg
Pharmaceutical Form: Injection
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subc
Sponsors
CHU de Bordeaux
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female; - Age between 18 and 75 years-old; - Adult patient with a diagnosis of RA as defined by the ACR/EULAR 2010 criteria for the classification of RA; - Patient who presents an inadequate response to one to four bDMARDs or tsDMARDs for at least 12 weeks prior to study entry at a dose that is considered acceptable to assess clinical response adequately; - Patient affected by active RA (DAS28-ESR > 3.2) eligible to receive a bDMARD or tsDMARD according to the French Society of Rheumatology guidelines; - Patient treated by prednisone dosage = 10mg per day. The corticosteroids dosage will be decreased to 7,5 mg/day at the beginning of the study (W0); - Person affiliated with or beneficiary of the French social security scheme; - Free, informed and written consent signed by the participant and the investigator (on the day of inclusion at the latest and before any examination required by the research project). 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 140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: - Patient previously treated with baricitinib or adalimumab for RA; - Patient affected by another form of inflammatory arthritis with the exception of secondary Sjögren syndrome; - Patient who presents contraindications to the study treatments; - Patient who is currently receiving corticosteroids at doses >10 mg of prednisone per day (or equivalent) or has been receiving an unstable dosing regimen of corticosteroids within 4 weeks of study entry; - Patient who is currently receiving more than 1 concomitant csDMARD (MTX, leflunomide, hydroxychloroquine or sulfasalazine) at the time of study entry; - Patient who is currently receiving or has received csDMARDs (eg, gold salts, cyclosporine, azathioprine, or any other immunosuppressives) other than MTX (up to 25 mg/week), leflunomide (up to 20 mg/day), hydroxychloroquine (up to 400 mg/day), or sulfasalazine (up to 3000 mg/day) within 4 weeks prior to study entry. - Patient who has received any parenteral corticosteroid administered by intramuscular or intravenous injection within 4 weeks prior to study entry, or is anticipated to require parenteral injection of corticosteroids during the study; - Patient who had 3 or more joints injected with intraarticular corticosteroids or hyaluronic acid within 4 weeks prior to study entry. Joints injected with intraarticular corticosteroids or hyaluronic acid within 2 weeks prior to study entry or within 6 weeks prior to planned randomization cannot be counted in the TJC and SJC for entry or enrollment purposes; - Patient with haemoglobin less than 80 g/L, absolute lymphocyte count lower than 0.5×109/L, absolute neutrophil count less than 1×109/L, or platelet count less than 100×109/L; clearance creatinine less than 60 mL/min; total bilirubin more than 1,5 times the upper limit of normal (ULN) at screening, aspartate aminotransferase, or alanine amino-transferase more than 2 times the upper limit of normal (ULN) at screening. - Patient with co-administration with OAT3 inhibitors with a strong inhibition potential (such as probenecid); - Patient who has a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data; - Patient who has a history of VTE (DVT/PE) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE). Prior DVT with PE where events overlapped in time (i.e., with PE considered resulting from DVT) is not considered recurrent DVT/PE for the purpose of this criterion; - Patient who has been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination). Investigators should review the vaccination status of their patients and follow the local guidelines for adult vaccination with nonlive vaccines intended to prevent infectious disease prior to entering patients into the study; - Patient with an active cancer; - Patient with malignancy or history of malignancy in the past 5 years, with the exception of adequately treated or excised non-metastatic basal-cell or squamous-cell cancer of the skin or cervical carcinoma in situ; - Patient who has a current or recent (<30 days prior to study entry) clin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the clinical efficacy at 24 weeks of the combination strategy of adalimumab (40 mg every two weeks) with baricitinib (4mg daily) versus baricitinib alone (4mg daily) in patients with refractory RA.;Secondary Objective: - To assess the safety of the combination of baricitinib and adalimumab versus baricitinib alone, comparing the clinical and biological safety profiles through 24 weeks of follow-up. - To assess the clinical efficacy of the combination of baricitinib and adalimumab versus baricitinib alone: - To assess drug retention rates at weeks 4, 12 and 24 in each treatment group; - To assess the proportion of patients who decrease the glucocorticosteroid dose = 5 mg per day, sustained from week 12 to week 24, among patients with a baseline dose > 5 mg per day, in each treatment group. - To assess patient-reported outcomes (HAQ, FACIT, RAID) at week 24 in each treatment group. - To assess the maintenance of clinical efficacy at week 52 in each treatment group.;Primary end point(s): Proportion of patients who achieve an ACR 50 response at week 24 in each treatment group (COMBI group (adalimumab + baricitinib) vs. MONO group (baricitinib conventional therapy)).;Timepoint(s) of evaluation of this end point: After 6 months of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of AEs and SAEs in each treatment group; - Proportion of patients who achieve an ACR20 response and an ACR70 response at weeks 4, 12 and 24 in each treatment group; - Proportion of patients who achieve an ACR50 response at weeks 4 and 12 in each treatment group - Proportion of patients who present a EULAR response at weeks 4, 12 and 24, according to DAS28-ESR, in each treatment group; - Proportion of patients who achieve remission or low disease activity at weeks 4, 12 and 24, according to DAS28-ESR, in each treatment group; - Quantitative change in DAS28-ESR, DAS28-CRP, sDAI and cDAI scores between baseline and each visit (until week 24 included) for each treatment group of treatment; - Drug retention rates at weeks 4, 12 and 24 in each treatment group; - Proportion of patients who decrease the glucocorticosteroid dose = 5 mg per day, sustained from week 12 to week 24, among patients with a baseline dose > 5 mg per day, in each treatment group; - Quantitative change in patient-reported outcomes (HAQ, FACIT, RAID) between baseline, weeks 4, 12 and 24 visit in each treatment group; - Proportion of participants maintaining an ACR50 response, remission or low disease activity at week 52 in each treatment group. - Quantitative change in DAS28-ESR, DAS28-CRP, sDAI and cDAI scores between weeks 24 and 52 in each treatment group.;Timepoint(s) of evaluation of this end point: After 12 months of inclusion | — |
Countries
France, Monaco
Contacts
Public ContactLaetitia LACAZE-BUZY
CHU de BORDEAUX
Outcome results
None listed