Phase IIb Study of Evobrutinib in Subjects With Rheumatoid Arthritis

NCT03233230 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MS200527-00602017-000384-32
• Study Type: interventional
• Target: 390
• Locations: 12 countries
• Sites: 98

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; American College of Rheumatology; High-sensitivity C-reactive protein; Bruton's tyrosine kinase

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12

  ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants \* 100.

  Week 12

Secondary Outcomes (36)

• Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12

  Week 12

• Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12

  Week 12

• Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50)

  Week 12

• Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70)

  Week 12

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

  up to Week 16

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

M2951 25 mg QD

EXPERIMENTAL

Drug: M2591 25 mg QD

M2951 75 mg QD

EXPERIMENTAL

Drug: M2951 75 mg QD

M2951 50 mg BID

EXPERIMENTAL

Drug: M2951 50 mg BID

Interventions

M2591 25 mg QD DRUG

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

Also known as: Evobrutinib

M2951 25 mg QD

M2951 75 mg QD DRUG

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

Also known as: Evobrutinib

M2951 75 mg QD

M2951 50 mg BID DRUG

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

Also known as: Evobrutinib

M2951 50 mg BID

Placebo DRUG

Participants received placebo matched to M2951 orally for 12 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• An hsCRP \>= 5.0 milligram/liter (mg/L) at Screening
• 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).

You may not qualify if:

• 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:

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (98)

Arizona Arthritis & Rheumatology Associates, P.C.

Phoenix, Arizona, 85032, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Phoenix, Arizona, 85037, United States

Location

East Bay Rheumatology Medical Group, Inc.

San Leandro, California, 94578, United States

Location

Omega Research Consultants

DeBary, Florida, 32713, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33603, United States

Location

McIlwain Medical Group, PA

Tampa, Florida, 33614, United States

Location

Medication Management, LLC

Greensboro, North Carolina, 27410, United States

Location

Arthritis Clinic Of Central Texas

San Marcos, Texas, 78666, United States

Location

Hospital Italiano de La Plata

La Plata, Buenos Aires, B1900AXI, Argentina

Location

Instituto de Investigaciones Clinicas

Mar del Plata, Buenos Aires, B7600FZ, Argentina

Location

Instituto Medico CER

Quilmes, Buenos Aires, B1878DVB, Argentina

Location

Instituto de Investigaciones Clinicas Quilmes

Quilmes, Buenos Aires, B1878GEG, Argentina

Location

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, San Miguel de Tucuman, T4000AXL, Argentina

Location

Centro de Investigaciones Reumatológicas

San Miguel de Tucumán, Tucumán Province, T4000BRD, Argentina

Location

Organizacion Medica de Investigacion (OMI)

Ciudad Autonoma Buenos Aires, C1015ABO, Argentina

Location

APRILLUS

Ciudad Autonoma Buenos Aires, C1046AAQ, Argentina

Location

Expertia S.A- Mautalen Salud e Investigación

Ciudad Autonoma Buenos Aires, C1128AAE, Argentina

Location

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

Ciudad Autonoma Buenos Aires, C1221ADC, Argentina

Location

ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas

Córdoba, X5000BNB, Argentina

Location

Instituto Reumatológico Strusberg

Córdoba, X5000EDC, Argentina

Location

Centro Polivalente de Asistencia e Inv. Clinica CER

San Juan, 5400, Argentina

Location

MHAT "Hadzhi Dimitar", OOD

Sliven, 8800, Bulgaria

Location

DCC "Alexandrovska", EOOD

Sofia, 1431, Bulgaria

Location

UMHAT "SofiaMed", OOD

Sofia, 1797, Bulgaria

Location

Centro Medico Prosalud

Santiago, 7500000, Chile

Location

Interin

Santiago, 7500010, Chile

Location

BioMedica Research Group

Santiago, 7500710, Chile

Location

Centro de Estudios Reumatologicos

Santiago, 7501126, Chile

Location

Centro de Reumatologia y Ortopedia SAS

Barranquilla, 080001, Colombia

Location

Riesgo de Fractura S.A.

Bogotá, 110221, Colombia

Location

Simedics Ips Sas

Bogotá, 111211, Colombia

Location

Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM

Bogotá, Colombia

Location

Servimed S.A.S.

Bucaramanga, 680003, Colombia

Location

Clinica de Artritis Temprana S.A.

Cali, 76001, Colombia

Location

Revmatolog, s.r.o

Jihlava, 586 01, Czechia

Location

CCBR Ostrava s.r.o.

Ostrava, 702 00, Czechia

Location

ARTROSCAN s.r.o.

Ostrava - Trebovice, 722 00, Czechia

Location

CLINTRIAL s.r.o.

Prague, 100 00, Czechia

Location

MUDR. Zuzana URBANOVA Revmatologie

Prague, 140 00, Czechia

Location

Thomayerova nemocnice

Praha 4 - Krc, 140 59, Czechia

Location

MUDR. Zuzana URBANOVA Revmatologie

Praha 4 Nusle, 140 00, Czechia

Location

MEDICAL PLUS s.r.o.

Uherské Hradiště, 686 01, Czechia

Location

PV-MEDICAL s.r.o.

Zlín, 760 01, Czechia

Location

Centro Investigacion en Artritis y Osteoporosis S.C.

Mexicali, Baja California Norte, 21200, Mexico

Location

Clinica de Investigacion en Reumatologia y Obesidad S.C.

Guadalajara, Jalisco, 44650, Mexico

Location

RM Pharma Specialists SA de CV

Mexico City, Mexico City, 03100, Mexico

Location

Investigacion y Biomedicina de Chihuahua, S.C.

Chihuahua City, 31000, Mexico

Location

Centro de Investigacion y Atencion Integral Durango CIAID

Durango, 34270, Mexico

Location

ClinicMed Daniluk, Nowak Spółka Jawna

Bialystok, 15-879, Poland

Location

Centrum Reumatologiczne Indywidualna Specjalistyczna Praktyka Lekarska lek. Barbara Bazela

Elblag, 82-300, Poland

Location

MCBK Iwona Czajkowska Anna Podrażka- Szczepaniak S.C.

Grodzisk Mazowiecki, 05-825, Poland

Location

Care Clinic

Katowice, 40-060, Poland

Location

Silmedic sp. z o.o

Katowice, 40-282, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla

Knurów, 44-190, Poland

Location

Malopolskie Centrum Medyczne s.c.

Krakow, 30-510, Poland

Location

Grazyna Pulka Specjalistyczny Osrodek "ALL-MED"

Krakow, 31-024, Poland

Location

GLOBE CLINICAL RESEARCH (Globe Badania Kliniczne Sp z o.o.)

Kłodzko, 57-300, Poland

Location

Centrum Badan Klinicznych S.C.

Poznan, 60-773, Poland

Location

RCMed

Sochaczew, 96-500, Poland

Location

Medycyna Kliniczna

Warsaw, 00-660, Poland

Location

Rheuma Medicus Zaklad Opieki Zdrowotnej

Warsaw, 02-118, Poland

Location

Centrum Medyczne AMED

Warsaw, 03-291, Poland

Location

Wojskowy Instytut Medyczny

Warsaw, 04-141, Poland

Location

Reum-Medica S.C Eliza Roszkowska

Wroclaw, 50-244, Poland

Location

Research Institute of Emergency Medical Care

Saint Petersburg, Sankt-Peterburg, 192242, Russia

Location

Limited Liability Company "Centre of Medical Common Practice"

Novosibirsk, 630091, Russia

Location

Ultramed

Omsk, 644024, Russia

Location

SPb SBIH "Clinical Rheumatological Hospital # 25"

Saint Petersburg, 190068, Russia

Location

LLC Medical Sanitary Unit#157

Saint Petersburg, 196066, Russia

Location

NIH "Departmental Hospital on Station Smolensk of OJSC "Russian Railways"

Smolensk, 214025, Russia

Location

SAIH of Yaroslavl region "Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev"

Yaroslavl, 150003, Russia

Location

SBHI of Yaroslavl Region "Clinical Hospital # 8"

Yaroslavl, 150003, Russia

Location

Institute of Rheumatology_Site 1

Belgrade, 11000, Serbia

Location

Military Medical Academy

Belgrade, 11000, Serbia

Location

Clinical Center Bezanijska kosa

Belgrade, 11080, Serbia

Location

Institute of Treatment and Rehabilitation "Niska Banja"

Niška Banja, 18205, Serbia

Location

General Hospital "Dr Laza K. Lazarevic" Sabac

Šabac, 15000, Serbia

Location

Wits Clinical Research

Johannesburg, Gauteng, 2193, South Africa

Location

Clinresco Centres (Pty) Ltd

Kempton Park, Gauteng, 1619, South Africa

Location

Emmed Research

Pretoria, Gauteng, 0002, South Africa

Location

University of Pretoria Clinical Research Unit

Pretoria, Gauteng, 0002, South Africa

Location

Naidoo, A

Durban, KwaZulu-Natal, 4319, South Africa

Location

Arthritis Clinical Research Trial Unit

Cape Town, Western Cape, 7405, South Africa

Location

Winelands Medical Research Centre

Stellenbosch, Western Cape, 7600, South Africa

Location

Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU

Ivano-Frankivsk, 76008, Ukraine

Location

GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine

Kharkiv, 61039, Ukraine

Location

Communal Institution of Healthcare Kharkiv City Clinical Hospital #8

Kharkiv, 61176, Ukraine

Location

Medical Center Medical Clinic Blagomed LLC

Kyiv, 01601, Ukraine

Location

Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC

Kyiv, 02091, Ukraine

Location

Medical Center of Revmotsentr LLC

Kyiv, 04070, Ukraine

Location

SI D.F.Chebotariov Institute of Gerontology of NAMSU

Kyiv, 04114, Ukraine

Location

CH of State Border Service of Ukraine (Military Base 2522) Dept of Therapy, D.Halytskyi Lviv NMU

Lviv, 79049, Ukraine

Location

M.V. Sklifosovskyi Poltava RCH Dept of Rheumatology HSEIU UMSA

Poltava, 36011, Ukraine

Location

A.Novak Transcarpathian Regional Clinical Hospital

Uzhhorod, 88000, Ukraine

Location

National Pirogov Memorial Medical University

Vinnytsia, 21018, Ukraine

Location

CI City Hospital #1

Zaporizhzhia, 69104, Ukraine

Location

CI Zaporizhzhia Regional Clinical Hospital of ZRC

Zaporizhzhia, 69600, Ukraine

Location

CI Zaporizhzhia Regional Clinical Hospital of ZRC

Zaporizhzhya, 69600, Ukraine

Location

Related Publications (2)

• Montalban X, Wallace D, Genovese MC, Tomic D, Parsons-Rich D, Bolay CL, Kao AH, Guehring H. A plain language summary of what clinical studies can tell us about the safety of evobrutinib - a potential treatment for multiple sclerosis. Neurodegener Dis Manag. 2023 Aug;13(4):207-213. doi: 10.2217/nmt-2023-0003. Epub 2023 Jun 22.

  PMID: 37345645 DERIVED

• Montalban X, Wallace D, Genovese MC, Tomic D, Parsons-Rich D, Le Bolay C, Kao AH, Guehring H. Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis. J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):1-9. doi: 10.1136/jnnp-2022-328799. Epub 2022 Nov 23.

  PMID: 36418156 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

evobrutinib; BID protein, human

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: July 28, 2017
• Study Start: September 18, 2017
• Primary Completion: September 23, 2019
• Study Completion: September 23, 2019
• Last Updated: September 28, 2020
• Results First Posted: September 28, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

AR (13); ZA (7); ME (5); UA (14); CZ (9); US (8); CO (6); RU (8); SE (5); BU (3); CL (4); PL (16)