BARICITINIB for Rheumatoid arthritis|Refractory rheumatoid arthritis

Inclusion criteria

• {"criterion_text":"- Age between 18 and 65 years-old\n- Adult patient with a diagnosis of RA as defined by the ACR/EULAR 2010 criteria for the classification of RA\n- Patient who presents an inadequate response to at least one bDMARD or tsDMARD for at least 12 weeks prior to study entry at a dose that is considered acceptable to assess clinical response adequately\n- Patient affected by active RA (DAS28-ESR > 3.2 or sDAI > 11 or cDAI > 10) eligible to receive a bDMARD or tsDMARD according to the French Society of Rheumatology guidelines\n- 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)\n- Person affiliated with or beneficiary of the French social security scheme\n- 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)"}

Exclusion criteria

• {"criterion_text":"- Patient previously treated with baricitinib\n- 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\n- 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 purpose\n- 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\n- Patient with co-administration with OAT3 inhibitors with a strong inhibition potential (such as probenecid).\n- 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\n- Patient with an history of Stevens-Johnson syndrome and/or cutaneous vasculitis.\n- Patient with an history of CNS demyelinating disorders and peripheral demyelinating polyneuropathies.\n- Patient with an history of Moderate to severe heart failure (NYHA classes III/IV)\n- Patient with an history of Major Adverse Cardiovascular Events (non-fatal myocardial infarction or non-fatal stroke).\n- 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\n- Patient previously treated by both adalimumab and etanercept. If the patient received previously only one of these two treatments, she/he can be included in the study but with the treatment she/he has not yet received (if she/he is randomized in the experimental COMBI group)\n- 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\n- Patient with an active cancer\n- Patient with malignancy or history of malignancy.\n- Patient who has a current or recent (<30 days prior to study entry) clinically serious viral, bacterial, fungal, or parasitic infection.\n- Patient who is immunocompromised and, in the opinion of the investigator, is at an unacceptable risk for participating in the study.\n- Patient with an history of sepsis or risk of sepsis.\n- Patient with a history of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).\n- Patient who had household contact with a person with active tuberculosis (TB) and did not receive appropriate and documented prophylaxis for TB.\n- Patient who has evidence of active TB or has previously had evidence of active TB and did not receive appropriate and documented treatment.\n- Patient who has evidence of latent TB (as documented by a positive PPD, no clinical symptoms consistent with active TB, and a normal chest x-ray at screening) unless patient completes at least 3 weeks of appropriate treatment prior to study entry and agrees to complete the remainder of treatment while in the trial\n- Patient affected by another form of inflammatory arthritis with the exception of secondary Sjögren syndrome\n- Patient who had any major surgery within 8 weeks prior to study entry or will require major surgery during the study that, in the opinion of the investigator, would pose an unacceptable risk to the patient.\n- Pregnant or breastfeeding woman, or woman of childbearing potential who refuses to use an effective contraception during the study course, and who does not take an effective contraception at least one week after baricitinib treatment, five months after adalimumab treatment and three weeks after etanercept treatment.\n- Patient governed by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).\n- Patient who presents contraindications to the study treatments\n- Patient with a history of hypersensitivity to etanercept/baricitinib/adalimumab and any of the excipients\n- Patient who smokes or has done so for a long time in the past\n- 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\n- Patient who is currently receiving more than 1 concomitant csDMARD (MTX, leflunomide, hydroxychloroquine or sulfasalazine) at the time of study entry\n- 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."}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Proportion of patients achieving ACR50 at week 24 in each treatment group (ACR50 response assessed at week 24)."}

Secondary endpoints

• {"endpoint_text":"- Main secondary endpoints : Proportion of AEs and SAEs in each treatment group","definition_or_measurement_approach":"Proportion (and counts) of adverse events (AEs) and serious adverse events (SAEs) recorded in each treatment group through the specified follow-up period."}
• {"endpoint_text":"- Proportion of patients who achieve an ACR20 response and an ACR70 response at weeks 4, 12 and 24 in each treatment group","definition_or_measurement_approach":"Proportion of patients achieving ACR20 and ACR70 at weeks 4, 12 and 24 in each treatment group."}
• {"endpoint_text":"- Proportion of patients who achieve an ACR50 response at weeks 4 and 12 in each treatment group","definition_or_measurement_approach":"Proportion of patients achieving ACR50 at weeks 4 and 12 in each treatment group."}
• {"endpoint_text":"- Proportion of patients who present a EULAR response at weeks 4, 12 and 24, according to DAS28-ESR, in each treatment group","definition_or_measurement_approach":"Proportion of patients meeting EULAR response criteria (assessed by DAS28-ESR) at weeks 4, 12 and 24 in each group."}
• {"endpoint_text":"- Proportion of patients who achieve remission or low disease activity at weeks 4, 12 and 24, according to DAS28-ESR, in each treatment group","definition_or_measurement_approach":"Proportion of patients meeting remission or low disease activity thresholds by DAS28-ESR at weeks 4, 12 and 24."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Mean/median change from baseline in DAS28-ESR, DAS28-CRP, sDAI and cDAI at each visit up to week 24 per treatment group."}
• {"endpoint_text":"- Drug retention rates at weeks 4, 12 and 24 in each treatment group","definition_or_measurement_approach":"Proportion of patients remaining on assigned treatment (drug retention) at weeks 4, 12 and 24 in each group."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion of patients with baseline prednisone >5 mg/day who reduce to ≤5 mg/day sustained from week 12 to week 24 in each group."}
• {"endpoint_text":"- Quantitative change in patient-reported outcomes (HAQ, FACIT, RAID) between baseline, weeks 4, 12 and 24 visit in each treatment group","definition_or_measurement_approach":"Change from baseline in patient-reported outcome scores (HAQ, FACIT, RAID) at weeks 4, 12 and 24 per group."}
• {"endpoint_text":"- Proportion of participants maintaining an ACR50 response, remission or low disease activity at week 52 in each treatment group.","definition_or_measurement_approach":"Proportion of participants who maintain ACR50, remission or low disease activity at week 52 in each group."}
• {"endpoint_text":"- Quantitative change in DAS28-ESR, DAS28-CRP, sDAI and cDAI scores between weeks 24 and 52 in each treatment group.","definition_or_measurement_approach":"Change in disease activity scores (DAS28-ESR, DAS28-CRP, sDAI, cDAI) between week 24 and week 52 for each group."}
• {"endpoint_text":"- Main secondary endpoints : Quantitative change in DAS28-CRP, between baseline and week 24 for each treatment group of treatment","definition_or_measurement_approach":"Change from baseline to week 24 in DAS28-CRP for each treatment group."}

France

Earliest CTIS Part Ii Submission Date

13-03-2024

Latest Decision Or Authorization Date

12-12-2024

Processing Time Days

274

Number Of Sites

35

Number Of Participants

169

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Bordeaux

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Biogen","duties_or_roles":"Monetary support (listed in sourceOfMonetarySupport)","organisation_type":""}
• {"country":"","full_name":"Eli Lilly and Company","duties_or_roles":"Monetary support (listed in sourceOfMonetarySupport)","organisation_type":""}
• {"country":"France","full_name":"Ministry for Health and Solidarity, France","duties_or_roles":"Monetary support (listed in sourceOfMonetarySupport)","organisation_type":""}