Rheumatoid Arthritis MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Evobrutinib
Product Code: M2951
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Evobrutinib
CAS Number: N/A
Current Sponsor code: M2951
Other descriptive name: M2951
Concent
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The current trial will enroll subjects who fulfill the following key inclusion criteria: • Consenting male or female subjects, 18 to 75 years of age • Confirmed diagnosis of RA according to 2010 ACR/EULAR RA classification criteria of at least 6 months duration prior to Screening • Persistently active moderate to severe RA at both Screening and Randomization (if significant surgical treatment of a joint has been performed, that joint cannot be counted for entry or enrollment purposes), as defined by: o = 6 swollen joints (of 66 assessed) and o = 6 tender joints (of 68 assessed). • An hsCRP = 5.0 mg/L (= 0.50 mg/dL) at Screening • Treatment for = 16 weeks with 7.5 to 25 mg/week MTX at a stable dose and route of administration (oral or parenteral) for at least 8 weeks prior to dosing with the IMP and maintained throughout the trial • For subjects entering the trial on MTX doses =65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: Subjects who fulfill any of the following key exclusion criteria should not be enrolled into this trial: • ACR functional class IV as defined by the ACR classification of functional status or wheelchair/bedbound • Use of oral corticosteroids > 10 mg daily prednisone equivalent, or change in dose of corticosteroids within 2 weeks prior to Screening or during Screening • Use of injectable corticosteroids (including intra-articular corticosteroids) or intra-articular hyaluronic acid within 4 weeks prior to Screening or during Screening • Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs) (including low-dose aspirin and COX-2 inhibitors) within 2 weeks prior to dosing with the IMP • High potency opioid analgesics are prohibited within 2 weeks prior to Screening and during the trial; other analgesics are allowed (e.g., acetaminophen, codeine, hydrocodone, propoxyphene, or tramadol), although not within 24 hours of study visits with clinical assessments. • Current or prior treatment with ANY of the following: o Biologic DMARDs (approved or investigational), including but not limited to: -TNF antagonists or biosimilars of these agents (approved or investigational), or any investigational TNF antagonist - Interleukin-6 antagonists - Abatacept (CTLA4-Fc) - Anakinra (IL-1 receptor antagonist) - B cell-depleting antibodies (e.g., rituximab, ocrelizumab, ofatumumab, obinutuzumab, ocaratuzumab, veltuzumab, or any biosimilars of these agents [approved or investigational]) - Anti-BLyS (B lymphocyte stimulator) agents (e.g., belimumab, tabalumab) - Dual BLyS/A proliferation-inducing ligand (APRIL) neutralizing agents (e.g., atacicept, RCT-18). o Targeted synthetic DMARDs (approved or investigational), specifically: - Janus kinase inhibitors - Other Bruton’s tyrosine kinase (BTK) inhibitors o Alkylating agents (e.g., chlorambucil, cyclophosphamide). • The following restrictions on non-biologic DMARD must be followed, otherwise the subject is excluded: o Auranofin (Ridaura®), minocycline, penicillamine, sulfasalazine, cyclosporine, mycophenolate, tacrolimus, azathioprine: must have been discontinued for 4 weeks prior to dosing with the IMP o Leflunomide (Arava®) must have been discontinued 12 weeks prior to dosing with the IMP if no elimination procedure is followed. Alternately, it should have been discontinued with the following elimination procedure at least 4 weeks prior to dosing with the IMP: Cholestyramine at a dosage of 8 g 3 times a day for at least 24 hours, or activated charcoal at a dosage of 50 g 4 times a day for at least 24 hours. o Injectable Gold (aurothiglucose or aurothiomalate): must have been discontinued for 8 weeks prior to dosing with the IMP o Anti-malarials (hydroxychloroquine, chloroquine) will be allowed in this trial. Subjects may be taking oral hydroxychloroquine (= 400 mg/day) or chloroquine (= 250 mg/day), doses must have been stable for at least 12 weeks prior to dosing with the IMP, and will need to be continued at that stable dose for the duration of the trial. If discontinued prior to this trial, they must have been discontinued for 4 weeks prior to dosing with the IMP. MRI Substudy Subjects: • Inability to comply with MRI scanning, including contraindications to MRI such as known allergy to gadolinium contrast media, claustrophobia (if the site does not have ability to scan extremities only), presence of a pacemaker, cochlear implants, ferromagnetic devices or cli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and dose response of 12 weeks of treatment with evobrutinib compared with placebo in subjects with rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR) on stable MTX therapy by assessment of the signs and symptoms of RA, as measured by American College of Rheumatology (ACR) 20% (ACR20) response assessed using high-sensitivity C-reactive protein (hsCRP) at Week 12;Secondary Objective: • To further evaluate the efficacy and dose response of 12 weeks of treatment with evobrutinib in MTX-IR subjects with RA on stable MTX therapy by assessment of the signs and symptoms of RA, as measured by DAS28-hsCRP low disease activity (DAS28 < 3.2) rate at Week 12 • To further evaluate the efficacy of 12 weeks of treatment with evobrutinib compared to placebo in MTX-IR subjects with RA on stable MTX therapy by assessment of the signs and symptoms of RA, as measured by DAS28-hsCRP remission (DAS28 < 2.6) rate at Week 12 • To further evaluate the efficacy and dose response of 12 weeks of treatment with evobrutinib in MTX-IR subjects with RA on stable MTX therapy by assessment of the signs and symptoms of RA, as measured by ACR50 and ACR70 at Week 12 • To evaluate the safety of evobrutinib in MTX-IR subjects with RA on stable MTX thera;Primary end point(s): Number of Subjects With ACR20 response assessed using hsCRP (ACR20-CRP) ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Number of subjects With DAS28-hsCRP low disease activity (DAS28 < 3.2) rate 2) Number of subjects With DAS28-hsCRP remission (DAS28 < 2.6) rate 3) Number of subjects with ACR 50% (ACR50) response assessed using hsCRP (ACR50-CRP) 4) Number of subjects with ACR 70% (ACR70) response assessed using hsCRP (ACR70-CRP) 5) Nature, severity and Occurrences of Subjects With of AEs and serious AEs (SAEs) 6)Absolute value in vital signs 7) Absolute value in ECG parameters including RR interval, PR interval, QRS duration, QT interval, and QTcF interval 8) Absolute value in Serum Ig levels (IgG, IgA, IgM) 9) Absolute value in Total B cell counts 10) Absolute value in Clinical laboratory parameters;Timepoint(s) of evaluation of this end point: 1-4:Week 12 5-10 Baseline up to Week 12 | — |
Countries
Argentina, Brazil, Bulgaria, Chile, Colombia, Czech Republic, Germany, Japan, Mexico, Poland, Russian Federation, Serbia, South Africa, Ukraine, United States
Contacts
Public ContactCommunication Center
Merck KGaA
Outcome results
None listed