The purpose of this study was to determine the efficacy, dose response, and safety of M52951 in participants with Rheumatoid Arthritis (RA), and to consider a dose to took forward into Phase III development.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

An hsCRP \>= 5.0 milligram/liter (mg/L) at Screening
In Japan, if a participant is less than (\<) 20 years, the written informed consent from the participant's parent or guardian will be required in addition to the participant's written consent.
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: \>= 6 swollen joints (of 66 assessed) and \>= 6 tender joints (of 68 assessed).
Treatment for \>= 16 weeks with 7.5 to 25 mg/week Methotrexate (MTX) at a stable dose and route of administration (oral or parenteral) for at least 8 weeks prior to dosing with the Investigational Medicinal Product (IMP) and maintained throughout the trial
For participants entering the trial on MTX doses \< 15 mg/week (\< 10 mg/week in Japan), there must be clear documentation in the medical record that higher doses of MTX were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines.
For MRI Sub-study participants, participants must have palpable synovitis of the wrist and/or \>= 1 of metacarpophalangeal joints 1 to 5, defined as loss of bony contours with palpable joint effusion and/or swelling, in the MRI-designated hand (that is., the hand being used in MRI assessments).

Criterios de exclusión

ACR functional class IV as defined by the ACR classification of functional status or wheelchair/bedbound
Use of oral corticosteroids greater than (\>) 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 cyclooxygenase-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 (that is, acetaminophen, codeine, hydrocodone\*, propoxyphene\*, or tramadol), although not within 24 hours of study visits with clinical assessments (\*not approved in Japan)
Current or prior treatment with any of the following:
Biologic Disease-modifying anti-rheumatic drugs (DMARDs) (approved or investigational), including but not limited to:
Tumor necrosis factor (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) (\*not approved in Japan)
B cell-depleting antibodies (example, rituximab, ocrelizumab\*, ofatumumab, obinutuzumab\*, ocaratuzumab\*, veltuzumab\*, or any biosimilars of these agents \[approved or investigational\]) (\*not approved in Japan)
Anti-BLyS (B lymphocyte stimulator) agents (example, belimumab, tabalumab\*) (\*not approved in Japan)
Dual BLyS/A proliferation-inducing ligand (APRIL) neutralizing agents (that is, atacicept\*, RCT-18\*) (\*not approved in Japan)
Targeted synthetic DMARDs, specifically:
Janus kinase inhibitors
Other Bruton's tyrosine kinase (BTK) inhibitors
Alkylating agents (example, chlorambucil\*, cyclophosphamide) (\*not approved in Japan).
The following restrictions on nonbiologic DMARD must be followed:
Auranofin (Ridaura), minocycline, penicillamine, sulfasalazine, cyclosporine, mycophenolate (mycophenolate sodium not approved in Japan), tacrolimus, azathioprine: must have been discontinued for 4 weeks prior to dosing with the IMP
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 gram 3 times a day for at least 24 hours, or activated charcoal at a dosage of 50 gram 4 times a day for at least 24 hours.
Injectable Gold (aurothioglucose\* or aurothiomalate): must have been discontinued for 8 weeks prior to dosing with the IMP (\*not approved in Japan)
Anti-malarials (hydroxychloroquine, chloroquine\*) will be allowed in this trial. Participants 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 (\*not approved in Japan).
For MRI Substudy:
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 clips, intracranial vascular clips, insulin pumps, and nerve stimulators.
More than 25% of applicable joints of the target hand and wrist having had prior surgery or showing maximum Genant-modified Sharp erosion (3.0) or joint-space narrowing (4.0) scores, based on single posteroanterior radiographs of target hand and wrist read centrally.

Intervenciones

drug

M2591 25 mg QD

Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.

drug

M2951 75 mg QD

Participants received 75 mg of M2951 orally QD for 12 weeks.

drug

M2951 50 mg BID

Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.

drug

Placebo

Participants received placebo matched to M2951 orally for 12 weeks.

Ubicaciones

Hospital Italiano de La Plata

La Plata, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas

Mar del Plata, Buenos Aires, Argentina

Instituto Medico CER

Quilmes, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Quilmes

Quilmes, Buenos Aires, Argentina

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, San Miguel de Tucuman, Argentina

Centro de Investigaciones Reumatológicas

San Miguel de Tucumán, Tucumán Province, Argentina

Organizacion Medica de Investigacion (OMI)

Ciudad Autonoma Buenos Aires, Argentina

APRILLUS

Ciudad Autonoma Buenos Aires, Argentina

Expertia S.A- Mautalen Salud e Investigación

Ciudad Autonoma Buenos Aires, Argentina

Hospital General de Agudos Dr. J. M. Ramos Mejia

Ciudad Autonoma Buenos Aires, Argentina

ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas

Córdoba, Argentina

Instituto Reumatológico Strusberg

Córdoba, Argentina

Centro Polivalente de Asistencia e Inv. Clinica CER

San Juan, Argentina

A Phase IIb, Randomized, Double-blind Study in Subjects With Rheumatoid Arthritis Evaluating the Safety and Efficacy of Evobrutinib Compared With Placebo in Subjects With an Inadequate Response to Methotrexate

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

M2591 25 mg QD

M2951 75 mg QD

M2951 50 mg BID

Placebo

Ubicaciones

Hospital Italiano de La Plata

Instituto de Investigaciones Clinicas

Instituto Medico CER

Instituto de Investigaciones Clinicas Quilmes

Centro Medico Privado de Reumatologia

Centro de Investigaciones Reumatológicas

Organizacion Medica de Investigacion (OMI)

APRILLUS

Expertia S.A- Mautalen Salud e Investigación

Hospital General de Agudos Dr. J. M. Ramos Mejia

ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas

Instituto Reumatológico Strusberg

Centro Polivalente de Asistencia e Inv. Clinica CER

Patrocinadores