MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis

NCT ID: NCT04512001

Last Updated: 2023-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 604 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-03
• Study Completion Date: 2022-06-06

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

MSB11456

Group Type: EXPERIMENTAL

MSB11456

Intervention Type: DRUG

Participants will receive MSB11456 subcutaneously, once a week.

RoActemra®

Group Type: ACTIVE_COMPARATOR

EU-approved RoActemra

Intervention Type: DRUG

Participants will receive EU-approved RoActemra® subcutaneously, once a week.

Interventions

MSB11456

Participants will receive MSB11456 subcutaneously, once a week.

Intervention Type: DRUG

EU-approved RoActemra

Participants will receive EU-approved RoActemra® subcutaneously, once a week.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fresenius Kabi SwissBioSim GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Medical Center Hipokrat 2000 OOD

Haskovo, Haskovo, Bulgaria

MHAT "Lyulin" EAD

Sofia, Sofia, Bulgaria

Military Medical Academy - Sofia

Sofia, Sofia, Bulgaria

Medical Center N.I.Pirogov EOOD

Sofia, Sofia, Bulgaria

Medical Center MedConsult Pleven

Pleven, , Bulgaria

University Multiprofile Hospital for Active Treatment Pulmed

Plovdiv, , Bulgaria

Multiprofile Hospital for Active Treatment Plovdiv

Plovdiv, , Bulgaria

Medical Center Teodora

Rousse, , Bulgaria

Diagnostic and Consultative Center Equita

Varna, , Bulgaria

MC Sanador M

Vidin, , Bulgaria

Revmatologie, s.r.o.

Brno, Jihormoravsky KRAJ, Czechia

Medical Plus

Uherské Hradiště, Jihormoravsky KRAJ, Czechia

Revmatologie MUDr. Zuzana Urbanova

Prague, Prague, Czechia

CCR Ostrava

Ostrava, Severomoravsky KRAJ, Czechia

Revmatologie MUDr. Klára Šírová s.r.o.

Ostrava, Severomoravsky KRAJ, Czechia

PV-Medical Services, s.r.o.

Zlín, Severomoravsky KRAJ, Czechia

Vesalion s.r.o.

Ostrava, , Czechia

Revmatologicky Ustav

Prague, , Czechia

Helsicore - Israeli Georgian Medical Research Clinic

Tbilisi, , Georgia

Research Institute of Clinical Medicine

Tbilisi, , Georgia

The First University Clinic

Tbilisi, , Georgia

EVEX Hospitals - Caraps Medline

Tbilisi, , Georgia

Tbilisi Heart and Vascular Clinic

Tbilisi, , Georgia

MediClub Georgia

Tbilisi, , Georgia

Georgian Dutch Hospital Ltd

Tbilisi, , Georgia

Mtskheta Street Clinic

Tbilisi, , Georgia

Tbilisi Heart Center

Tbilisi, , Georgia

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye, Hungary

Csongrad Megyei Dr. Bugyi Istvan Korhaz

Szentes, Csongrád megye, Hungary

DRC Gyogyszervizsgalo Kozpont Kft.

Székesfehérvár, Fejér, Hungary

SALDINVEST Befektetesi es Vagyonkezelo Korlatolt Felelossegu Tarsasag

Székesfehérvár, Fejér, Hungary

Integrity Gyogyaszati Kozpont

Zalaegerszeg, Zala County, Hungary

Revita Reumatologiai Rendelo

Budapest, , Hungary

MÁV Kórház és Rendelőintézet Rheumatológia

Szolnok, , Hungary

Vital Medical Center Orvosi es Fogaszati Kozpont

Veszprém, , Hungary

Institutia Medico-Sanitara Publica Institutul de Cardiologie

Chisinau, , Moldova

Spitalul Clinic Republican

Chisinau, , Moldova

IMSP Spitalul Clinic Municipal Sfanta Treime

Chisinau, , Moldova

Instituţia Medico-Sanitară Publică Institutul de Cardiologie

Chisinau, , Moldova

Solumed Centrum Medyczne

Poznan, Greater Poland Voivodeship, Poland

Centrum Badan Klinicznych S.C.

Poznan, Greater Poland Voivodeship, Poland

Ai Centrum Medyczne

Poznan, Greater Poland Voivodeship, Poland

Centrum Medyczne HCP

Poznan, Greater Poland Voivodeship, Poland

Nasz Lekarz Osrodek Badan Klinicznych - Bydgoszcz

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Nasz Lekarz Przychodnie Medyczne

Torun, Kuyavian-Pomeranian Voivodeship, Poland

Grazyna Pulka Specjalistyczny Osrodek All-med

Krakow, Lesser Poland Voivodeship, Poland

Pratia MCM Krakow

Krakow, Lesser Poland Voivodeship, Poland

WroMedica

Wroclaw, Lower Silesian Voivodeship, Poland

Centrum Medyczne Oporow

Wroclaw, Lower Silesian Voivodeship, Poland

Samodzielny Publiczny Zespol Opieki Zdrowotnej w Tomaszow Lubelski

Tomaszów Lubelski, Lublin Voivodeship, Poland

Twoja Przychodnia-Centrum Medyczne Nowa Sol

Nowa Sól, Lubusz Voivodeship, Poland

RCMed Oddzial Sochaczew

Sochaczew, Masovian Voivodeship, Poland

Medycyna Kliniczna

Warsaw, Masovian Voivodeship, Poland

Rheuma Medicus Zaklad Opieki Zdrowotnej

Warsaw, Masovian Voivodeship, Poland

Ars Rheumatica - Reumatika Centrum Reumatologii

Warsaw, Masovian Voivodeship, Poland

Barwijuk Clinics

Warsaw, Masovian Voivodeship, Poland

Centrum Medyczne AMED Warszawa Targowek

Warsaw, Masovian Voivodeship, Poland

SANUS Szpital Specjalistyczny

Stalowa Wola, Podkarpackie Voivodeship, Poland

Osteo-Medic

Bialystok, Podlaskie Voivodeship, Poland

ClinicMed Daniluk Nowak Spolka Jawna

Bialystok, Podlaskie Voivodeship, Poland

Centrum Medyczne Pratia w Gdyni

Gdynia, Pomeranian Voivodeship, Poland

Silmedic w Swidniku

Katowice, Silesian Voivodeship, Poland

Ambulatorium Sp. z

Elblag, Warmian-Masurian Voivodeship, Poland

Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spolka Partnerska

Elblag, Warmian-Masurian Voivodeship, Poland

Centrum Terapii Wspolczesnej

Lodz, Łódź Voivodeship, Poland

TRIALMED CRS Piotrków Trybunalski

Piotrkow Trybunalski, Łódź Voivodeship, Poland

Clinical Rheumatological Hospital Number 25

Saint Petersburg, Sankt-Peterburg, Russia

Kazan State Medical University

Kazan', Tatarstan Republic, Russia

State Budgetary Healthcare Institution of the Yaroslavl Region Clinical Hospital No. 2

Yaroslavl, Yaroslavlr, Russia

Chelyabinsk Regional Clinical Hospital

Chelyabinsk, , Russia

Medical Center Revma-Med

Kemerovo, , Russia

NIARMEDIK - Clinic on Clinic on Kitai Gorod

Moscow, , Russia

Medical Center Health Family

Novosibirsk, , Russia

Polyclinic of Private Security Personnel

Saint Petersburg, , Russia

Saratov Regional Clinical Hospital

Saratov, , Russia

Departmental Hospital at Smolensk Station of JSC RZhD

Smolensk, , Russia

Biomed

Vladimir, , Russia

CjSC "Center of Family Medicine"

Yekaterinburg, , Russia

Institute of Rheumatology

Belgrade, , Serbia

Institut za Lecenje i Rehabilitaciju Niška Banja

Niška Banja, , Serbia

Specijalna Bolnica za Reumatske bolesti Novi Sad

Novi Sad, , Serbia

General Hospital Djordje Jovanovic Zrenjanin

Zrenjanin, , Serbia

REUMEX s.r.o.

Rimavská Sobota, , Slovakia

LERAM s.r.o.

Topoľčany, , Slovakia

ALBAMED s.r.o.

Zvolen, , Slovakia

Countries

Bulgaria; Czechia; Georgia; Hungary; Moldova; Poland; Russia; Serbia; Slovakia

References

Zubrzycka-Sienkiewicz A, Klama K, Ullmann M, Petit-Frere C, Baker P, Monnet J, Illes A. Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study. RMD Open. 2024 Feb 5;10(1):e003596. doi: 10.1136/rmdopen-2023-003596.

Reference Type: DERIVED

PMID: 38316489 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-004369-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FKS456-001

Identifier Type: -

Identifier Source: org_study_id