MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis

Phase 3

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: MSB11456
Drug: EU-approved RoActemra

Registration Number: NCT04512001

Lead Sponsor: Fresenius Kabi SwissBioSim GmbH

Brief Summary: The purpose of the study is to compare the efficacy, safety and immunogenicity of MSB11456 and EU approved RoActemra® in participants with moderately to severely active rheumatoid arthritis.

Participants will be randomized at the beginning of the Core Treatment Period (Baseline to Week 24) to receive either MSB11456 or EU approved RoActemra® once a week (QW). At the beginning of the Extended Treatment Period (Week 24 to Week 52), participants who received RoActemra® will be re-randomized to either continue receiving RoActemra® QW or switch to receive MSB11456 QW.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 604

Inclusion Criteria

Are ≥18 years of age.
Diagnosis of rheumatoid arthritis according to the revised 1987 ACR/European League Against Rheumatism (EULAR) Classification 2010 criteria with disease duration of ≥6 months.
Have moderately to severely active rheumatoid arthritis.
Must have been treated with methotrexate for at least 12 consecutive weeks immediately prior to randomization and are on a stable dose between 10 and 25 mg/week methotrexate for the last 8 weeks prior to screening.
Have had previous inadequate clinical response to at least one modifying anti-rheumatic drug.
Women of childbearing potential (i.e., considered fertile following menarche and until becoming postmenopausal unless permanently sterile) can participate only if they have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1 before randomization. Women of childbearing potential must have used and agree to use a highly effective contraception (i.e., methods with a failure rate of less than 1% per year), for 4 weeks before randomization and must agree to continue to practice adequate contraception for 3 months after the last study drug administration.
Must voluntarily give written informed consent before any study-related activities are performed. Participants must read and fully understand the Informed Consent Form and the requirements of the study. Participants must be willing to comply with all study visits and assessments. Participants must be willing to complete each study procedure. Note: A separate Informed Consent Form (containing important information about COVID 19, clinical research study participation and participant consent) will be provided to and signed by each participant to provide information on the general risks of study participation related to COVID-19 and to document that it is understood by the participant. Another separate Informed Consent Form will be required to be understood and signed by partners of male participating patients who become pregnant during the study or within 10 weeks after the participating patient's last dose of study drug.

Exclusion Criteria

American College of Rheumatology functional class IV as defined by the ACR classification of functional status or wheelchair/bedbound.
Previously received tocilizumab, an investigational or licensed biosimilar of tocilizumab or any interleukin-6 acting drugs.
Prior use of targeted synthetic disease-modifying anti-rheumatic drugs like janus kinase inhibitors.
Prior use of more than 2 biologic treatments for rheumatoid arthritis.
Received a live or attenuated vaccine within 4 weeks prior to randomization.
Participant is considered by the Investigator, for any reason, to be an unsuitable candidate for the study. Investigator should specifically evaluate the participant's eligibility taking into consideration COVID-19 risk factors and situation.
Has a serious and/or unstable and/or poorly controlled medical condition such as but not limited to poorly controlled diabetes, unstable ischemic heart disease, uncontrolled hypertension or other cardiovascular, cerebrovascular, cardiovascular, gastrointestinal disease, hepatic, renal, hematological, endocrine, nervous system or pulmonary disease or other relevant medical condition or a history of clinically significant disease or any other condition that, in the opinion of the Investigator, would put the participant at risk by participation in the study.
Confirmed or, based on the signs and symptoms observed at the time of assessment, suspected active COVID-19 infection at the time of screening and/or randomization.
Has had any infection as follows:
1. Herpes zoster or any opportunistic invasive infection within 6 months of screening.
2. Frequent, chronic or recurrent infections.
3. A positive test for human immunodeficiency virus subtype 1 (HIV-1) or 2 (HIV-2), hepatitis C antibody, hepatitis B surface antigen and/or core antibody for immunoglobulin G and/or immunoglobulin M or total immunoglobulin at screening.
4. A serious infection within 8 weeks prior to randomization.
5. Required treatment with oral antibiotics and/or anti-fungal drugs within 14 days prior to randomization.
Medical evidence of active or latent tuberculosis as indicated by a positive QuantiFERON®-TB Gold Plus test, chest X-ray and/or clinical examination or has had active or latent tuberculosis disease at any time in the past.
Received a COVID 19 vaccine within 4 weeks prior to randomization, are receiving ongoing COVID-19 vaccination at the time of screening or plan to receive COVID-19 vaccination before the completion of the Week 30 visit of the study. COVID-19 vaccination is considered ongoing if a multidose regimen has been started but has not been completed.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSB11456	MSB11456	-
RoActemra®	EU-approved RoActemra	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)	Baseline; Week 24	The DAS28-ESR is a measure of disease activity in 28 joints that consists of a composite numerical score of the following variables: Tender Joint Count (TJC), Swollen Joint Count (SJC), erythrocyte sedimentation rate (ESR) and Patient's Global Assessment of Disease Activity. The DAS28-ESR score was derived using the formula: DAS28-ESR = 0.56\√(TJC28) + 0.28\√(SJC28) + 0.014\GH + 0.70\Ln(ESR), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity on a scale of 1 to 100 where 100 is maximal activity). Higher values mean a higher disease activity. The level of disease activity can be interpreted as: * Remission (score of \<2.6). * Low (score of ≤2.6 to \<3.2). * Moderate (score of ≤3.2 to ≤5.1). * High (score of \>5.1) A negative change from baseline indicates an improvement.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With 20% Improvement in American College of Rheumatology (ACR20) Response	Baseline; Week 24	ACR20 was defined as the number of participants with at least 20% improvement from baseline in number of tender and swollen joints (68/66 joint count), and at least 20% improvement from baseline in three or more of the 5 ACR Core Set measures: * Patient's Assessment of Arthritis Pain * Physical Function Assessment (Health Assessment Questionnaire-Disability Index) * Acute phase reactant level (erythrocyte sedimentation rate or C-reactive protein) * Patient's Global Assessment of Disease Activity and * Physician's Global Assessment of Disease Activity
Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE)	Baseline to end of study, up to Week 63
Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE)	Baseline to end of study, up to Week 63
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16; Extended Period Baseline (Week 24), Week 30, Week 42, and Week 52	The DAS28-ESR is a measure of disease activity in 28 joints that consists of a composite numerical score of the following variables: TJC, SJC, ESR and Patient's Global Assessment of Disease Activity. The DAS28-ESR score was derived using the formula: DAS28-ESR = 0.56\√(TJC28) + 0.28\√(SJC28) + 0.014\GH + 0.70\Ln(ESR), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity on a scale of 1 to 100 where 100 is maximal activity). Higher values mean a higher disease activity. The level of disease activity can be interpreted as: * Remission (score of \<2.6). * Low (score of ≤2.6 to \<3.2). * Moderate (score of ≤3.2 to ≤5.1). * High (score of \>5.1) A negative change from baseline indicates an improvement. For weeks 30, 42 and 52, the extended baseline (week 24) was used for the change in DAS28-ESR calculation.
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs)	Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Anti-Drug Antibodies (ADAs) Titer Levels	Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Percentage of Participants With Neutralizing Antibodies (NAb)	Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55

Trial Locations

Locations (85): Csongrad Megyei Dr. Bugyi Istvan Korhaz
🇭🇺
Szentes, Csongrad, Hungary
IMSP Spitalul Clinic Municipal Sfanta Treime
🇲🇩
Chisinau, Moldova, Republic of
DRC Gyogyszervizsgalo Kozpont Kft.
🇭🇺
Szekesfehervar, Fejer, Hungary
SALDINVEST Befektetesi es Vagyonkezelo Korlatolt Felelossegu Tarsasag
🇭🇺
Szekesfehervar, Fejer, Hungary
Centrum Terapii Wspolczesnej
🇵🇱
Lodz, Lodzkie, Poland
Vital Medical Center Orvosi es Fogaszati Kozpont
🇭🇺
Veszprem, Hungary
Integrity Gyogyaszati Kozpont
🇭🇺
Zalaegerszeg, Zala, Hungary
MÁV Kórház és Rendelőintézet Rheumatológia
🇭🇺
Szolnok, Hungary
Institutia Medico-Sanitara Publica Institutul de Cardiologie
🇲🇩
Chisinau, Moldova, Republic of
Spitalul Clinic Republican
🇲🇩
Chisinau, Moldova, Republic of
Centrum Medyczne AMED Warszawa Targowek
🇵🇱
Warszawa, Mazowieckie, Poland
SANUS Szpital Specjalistyczny
🇵🇱
Stalowa Wola, Podkarpackie, Poland
ClinicMed Daniluk Nowak Spolka Jawna
🇵🇱
Bialystok, Podlaskie, Poland
Silmedic w Swidniku
🇵🇱
Katowice, Slaskie, Poland
CjSC "Center of Family Medicine"
🇷🇺
Ekaterinburg, Russian Federation
Saratov Regional Clinical Hospital
🇷🇺
Saratov, Russian Federation
Medical Center Revma-Med
🇷🇺
Kemerovo, Russian Federation
Polyclinic of Private Security Personnel
🇷🇺
Saint Petersburg, Russian Federation
REUMEX s.r.o.
🇸🇰
Rimavska Sobota, Slovakia
Departmental Hospital at Smolensk Station of JSC RZhD
🇷🇺
Smolensk, Russian Federation
Biomed
🇷🇺
Vladimir, Russian Federation
General Hospital Djordje Jovanovic Zrenjanin
🇷🇸
Zrenjanin, Serbia
Helsicore - Israeli Georgian Medical Research Clinic
🇬🇪
Tbilisi, Georgia
Vesalion s.r.o.
🇨🇿
Ostrava, Czechia
Medical Center Hipokrat 2000 OOD
🇧🇬
Haskovo, Khaskovo, Bulgaria
MHAT "Lyulin" EAD
🇧🇬
Sofia, Sofiya, Bulgaria
Military Medical Academy - Sofia
🇧🇬
Sofia, Sofiya, Bulgaria
Medical Center MedConsult Pleven
🇧🇬
Pleven, Bulgaria
Multiprofile Hospital for Active Treatment Plovdiv
🇧🇬
Plovdiv, Bulgaria
MC Sanador M
🇧🇬
Vidin, Bulgaria
The First University Clinic
🇬🇪
Tbilisi, Georgia
EVEX Hospitals - Caraps Medline
🇬🇪
Tbilisi, Georgia
Diagnostic and Consultative Center Equita
🇧🇬
Varna, Bulgaria
Medical Plus
🇨🇿
Uherské Hradiště, Jihormoravsky KRAJ, Czechia
MediClub Georgia
🇬🇪
Tbilisi, Georgia
Georgian Dutch Hospital Ltd
🇬🇪
Tbilisi, Georgia
Revmatologie, s.r.o.
🇨🇿
Brno, Jihormoravsky KRAJ, Czechia
Revmatologie MUDr. Zuzana Urbanova
🇨🇿
Praha 4, Praha, Czechia
Mtskheta Street Clinic
🇬🇪
Tbilisi, Georgia
CCR Ostrava
🇨🇿
Ostrava, Severomoravsky KRAJ, Czechia
PV-Medical Services, s.r.o.
🇨🇿
Zlin, Severomoravsky KRAJ, Czechia
Medical Center N.I.Pirogov EOOD
🇧🇬
Sofia, Sofiya, Bulgaria
University Multiprofile Hospital for Active Treatment Pulmed
🇧🇬
Plovdiv, Bulgaria
Medical Center Teodora
🇧🇬
Ruse, Bulgaria
Revmatologicky Ustav
🇨🇿
Praha, Czechia
Revita Reumatologiai Rendelo
🇭🇺
Budapest, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺
Szeged, Csongrad, Hungary
Centrum Medyczne Oporow
🇵🇱
Wroclaw, Dolnoslaskie, Poland
Medycyna Kliniczna
🇵🇱
Warszawa, Mazowieckie, Poland
Grazyna Pulka Specjalistyczny Osrodek All-med
🇵🇱
Krakow, Malopolskie, Poland
Rheuma Medicus Zaklad Opieki Zdrowotnej
🇵🇱
Warszawa, Mazowieckie, Poland
Samodzielny Publiczny Zespol Opieki Zdrowotnej w Tomaszow Lubelski
🇵🇱
Tomaszow Lubelski, Lubelskie, Poland
TRIALMED CRS Piotrków Trybunalski
🇵🇱
Piotrków Trybunalski, Lodzkie, Poland
Twoja Przychodnia-Centrum Medyczne Nowa Sol
🇵🇱
Nowa Sol, Lubuskie, Poland
Pratia MCM Krakow
🇵🇱
Krakow, Malopolskie, Poland
Ars Rheumatica - Reumatika Centrum Reumatologii
🇵🇱
Warszawa, Mazowieckie, Poland
Barwijuk Clinics
🇵🇱
Warszawa, Mazowieckie, Poland
Osteo-Medic
🇵🇱
Bialystok, Podlaskie, Poland
Centrum Medyczne Pratia w Gdyni
🇵🇱
Gdynia, Pomorskie, Poland
Clinical Rheumatological Hospital Number 25
🇷🇺
Saint-Petersburg, Saint Petersburg, Russian Federation
Ambulatorium Sp. z
🇵🇱
Elblag, Warminsko-mazurskie, Poland
Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spolka Partnerska
🇵🇱
Elblag, Warminsko-mazurskie, Poland
Ai Centrum Medyczne
🇵🇱
Poznan, Wielkopolskie, Poland
Centrum Badan Klinicznych S.C.
🇵🇱
Poznan, Wielkopolskie, Poland
State Budgetary Healthcare Institution of the Yaroslavl Region Clinical Hospital No. 2
🇷🇺
Yaroslavl, Yaroslavlr, Russian Federation
Chelyabinsk Regional Clinical Hospital
🇷🇺
Chelyabinsk, Russian Federation
NIARMEDIK - Clinic on Clinic on Kitai Gorod
🇷🇺
Moscow, Russian Federation
Medical Center Health Family
🇷🇺
Novosibirsk, Russian Federation
LERAM s.r.o.
🇸🇰
Topolcany, Slovakia
Revmatologie MUDr. Klára Šírová s.r.o.
🇨🇿
Ostrava, Severomoravsky KRAJ, Czechia
Kazan State Medical University
🇷🇺
Kazan, Tatarstan, Russian Federation
Nasz Lekarz Przychodnie Medyczne
🇵🇱
Torun, Kujawsko-pomorskie, Poland
Institute of Rheumatology
🇷🇸
Belgrade, Serbia
Institut za Lecenje i Rehabilitaciju Niška Banja
🇷🇸
Niška Banja, Serbia
ALBAMED s.r.o.
🇸🇰
Zvolen, Slovakia
Research Institute of Clinical Medicine
🇬🇪
Tbilisi, Georgia
Tbilisi Heart Center
🇬🇪
Tbilisi, Georgia
WroMedica
🇵🇱
Wroclaw, Dolnoslaskie, Poland
RCMed Oddzial Sochaczew
🇵🇱
Sochaczew, Mazowieckie, Poland
Centrum Medyczne HCP
🇵🇱
Poznan, Wielkopolskie, Poland
Nasz Lekarz Osrodek Badan Klinicznych - Bydgoszcz
🇵🇱
Bydgoszcz, Kujawsko-pomorskie, Poland
Tbilisi Heart and Vascular Clinic
🇬🇪
Tbilisi, Georgia
Instituţia Medico-Sanitară Publică Institutul de Cardiologie
🇲🇩
Chisinau, Moldova, Republic of
Solumed Centrum Medyczne
🇵🇱
Poznan, Wielkopolskie, Poland
Specijalna Bolnica za Reumatske bolesti Novi Sad
🇷🇸
Novi Sad, Serbia