rheumatoid arthritis MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Olumiant
Product Name: Olumiant
Pharmaceutical Form: Coated tablet
INN or Proposed INN: BARICITINIB
CAS Number: 1187594-09-7
Concentration unit: mg milligram(s)
Concentration type: equal
C
Sponsors
Fundación Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient able to provide written informed consent 2. Mentally competent to understand and willing to undergo the scheduled study procedures, including study questionnaires as established in the protocol. 3. Female or male, from 18 to 75 years of age at the moment of informed consent signature. 4. Patient with RA diagnosed according to 2010 ACR/EULAR Classification Criteria for RA. 5. Moderate to severe disease activity (according to Disease Activity Score for 28 joints (DAS28) = 3.2). 6. Inadequate response to MTX, which must have been received during, at least, 3 months prior to baseline visit and be on a stable dose of = 25 mg/week. 7. Patients who fulfils the pre-requisites for biologic and targeted synthetic disease modifying antirheumatic drugs (DMARD) therapy according to National recommendations/regulations (eg, absence of active infections, absence of latent tuberculosis, recommendations regarding previous cancer, vaccination recommendations,…). 8. Written acceptance to use highly effective contraception i.e. intrauterine device (IUD); hormonal therapy (progestin alone or combined with estrogen) associated with inhibition of ovulation such as oral pill, injection, implant, transdermal patch or vaginal ring; tubal ligation, partner’s vasectomy; or sexual abstinence for the entire duration of study participation including six months after stop of study treatment. 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 170 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Patient considered by the investigator to be unsuitable for the study treatment and/or rescue medication (RM) based on the prescription drug labeling, their medical history, physical examination, concomitant medication (CM) and concomitant systemic diseases. 2. Complications during the period prior to randomisation, in the investigator's opinion. 3. Hypersensitivity or allergy to the study medication. 4. Patients taking any concomitant medication, which could be susceptible to interact with the study drugs. 5. Patients in treatment with any medication that could affect the evaluation of the study treatment’s efficacy. DMARDs other than methotrexate are not allowed at study inclusion. If the patient has received other DMARD, eg hidroxicloroquine, leflunomide, sulphasalazine,....These drugs must have been stopped at least 3 months before inclusion. Regarding NSAID or corticosteroids, concomitant stable doses of nonsteroidal anti-inflammatory drugs, analgesics for pain relief if necessary. or corticosteroids (= 7.5mg of prednisone or the equivalent daily) will be allowed during the trial period. 6. Patients on anticoagulant treatment 7. Pregnant or lactating women. 8. Patients and/or female partners of male patients not using highly effective method of birth control i.e. intrauterine device (IUD); hormonal therapy (progestin alone or combined with estrogen) associated with inhibition of ovulation such as oral pill, injection, implants, transdermal patch or vaginal ring; tubal ligation, partner’s vasectomy; or sexual abstinence.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the study is to demonstrate non-inferiority of the response of MSKUS-assessed synovitis (i.e. B-mode and Doppler mode synovitis) to baricitinib treatment, alone plus combined with MTX (arm1 + arm2) vs. etanercept plus MTX (arm 3) in IR-MTX patients. Non-inferiority will be claimed if changes in MSKUS-assessed synovitis with baricitinib (alone and combined with MTX) after 12 weeks of treatment is at least 80% of changes in the etanercept + MTX group in the same period using a non-inferiority test for two means.;Secondary Objective: •To compare the grade of B-mode- and Doppler-detected residual synovitis in IR-MTX RA patients who achieve clinical remission or low disease activity (i.e. DAS28 <3.2) at 4 weeks, 12 weeks and 24 weeks on baricitinib + MTX vs baricitinib monotherapy vs + etanercept + MTX. •To evaluate the predictive value of MSKUS-assessed response to baricitinib (monotherapy and combined with MTX) at week 4 in relation to clinical and MSKUS response at week 12 and 24. •To histologically evaluate synovial biopsies, obtained at baseline (26, 27) in baricitinib + MTX treated patients in comparison to that observed in etanercept + MTX therapy, in correlation with the results obtained by MSKUS studies. The gene expression and synthesis of proinflammatory mediators (TNF, IL6, IL1, COX2, MCP1, pSTAT1, pSTAT2, pSTAT3, SOCS1, SOCS2, SOCS3, pERK, pAKT…) by real-time PCR and Western-Blot techniques will be assessed. ...;Primary end point(s): Efficacy: The primary outcome considered in this trial is the decrease in join inflammation detected by MSKUS (B-mode and Doppler mode synovitis). Safety: Safety evaluation will be assessed through physical examination, possible adverse events (related or not to the treatment under study) and analytical parameters. During each study visit all the safety variables must be recorded in medical records and e-CRF. ;Timepoint(s) of evaluation of this end point: 4, 12, 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary: The secondary endpoints will be: • Time-point of significant change in B-mode and Doppler synovitis according to treatment group (4 weeks, 12 weeks, 24 weeks). • Presence and amount of subclinical B-mode and Doppler synovitis in patients reaching DAS28-defined clinical remission and low disease activity at 4 weeks, 12 weeks and 24 weeks, according to treatment group. • Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) at 4 weeks, 12 weeks and 24 weeks, according to treatment group. • Correlation between presence of MSKUS-assessed synovitis, synovial histological alterations and the presence of proinflammatory citokines (TNF, IL6, IL1, COX2, MCP1, RANKL, OPG…) in serum and synovial tissue, at baseline in all patients and after 12 weeks in patients classified as non-responders, according to treatment group. • Changes in PROM as assessed by the Health Assessment Questionnaire–Disability Index (HAQ-DI), from baseline to 24 weeks. ;Timepoint(s) of evaluation of this end point: 4, 12, 24 weeks | — |
Countries
Belgium, Denmark, Portugal, Spain
Contacts
Public ContactClinical Operations
Adknoma Health Research S.L.
Outcome results
None listed