MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis

NCT04512001 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: FKS456-0012019-004369-42
• Study Type: interventional
• Target: 604
• Locations: 9 countries
• Sites: 85

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

Keywords

MSB11456; RoActemra®

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)

  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.

  Baseline; Week 24

Secondary Outcomes (7)

• 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

• Number of Participants With 20% Improvement in American College of Rheumatology (ACR20) Response

  Baseline; Week 24

• 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

• Percentage of Participants With Positive Anti-Drug Antibodies (ADAs)

  Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55

Study Arms (2)

MSB11456

EXPERIMENTAL

Drug: MSB11456

RoActemra®

ACTIVE COMPARATOR

Drug: EU-approved RoActemra

Interventions

MSB11456 DRUG

Participants will receive MSB11456 subcutaneously, once a week.

MSB11456

EU-approved RoActemra DRUG

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

RoActemra®

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Herpes zoster or any opportunistic invasive infection within 6 months of screening.
• Frequent, chronic or recurrent infections.
• 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.
• A serious infection within 8 weeks prior to randomization.
• 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.

Sponsors & Collaborators

• Fresenius Kabi SwissBioSim GmbH: lead

Study Sites (85)

Medical Center Hipokrat 2000 OOD

Haskovo, Haskovo, 6300, Bulgaria

Location

MHAT "Lyulin" EAD

Sofia, Sofia, 1336, Bulgaria

Location

Military Medical Academy - Sofia

Sofia, Sofia, 1606, Bulgaria

Location

Medical Center N.I.Pirogov EOOD

Sofia, Sofia, 1612, Bulgaria

Location

Medical Center MedConsult Pleven

Pleven, 5800, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Pulmed

Plovdiv, 4002, Bulgaria

Location

Multiprofile Hospital for Active Treatment Plovdiv

Plovdiv, 4003, Bulgaria

Location

Medical Center Teodora

Rousse, 7012, Bulgaria

Location

Diagnostic and Consultative Center Equita

Varna, 9002, Bulgaria

Location

MC Sanador M

Vidin, 3703, Bulgaria

Location

Revmatologie, s.r.o.

Brno, Jihormoravsky KRAJ, 638 00, Czechia

Location

Medical Plus

Uherské Hradiště, Jihormoravsky KRAJ, 686 01, Czechia

Location

Revmatologie MUDr. Zuzana Urbanova

Prague, Prague, 140 00, Czechia

Location

CCR Ostrava

Ostrava, Severomoravsky KRAJ, 702 00, Czechia

Location

Revmatologie MUDr. Klára Šírová s.r.o.

Ostrava, Severomoravsky KRAJ, 702 00, Czechia

Location

PV-Medical Services, s.r.o.

Zlín, Severomoravsky KRAJ, 760 01, Czechia

Location

Vesalion s.r.o.

Ostrava, 702 00, Czechia

Location

Revmatologicky Ustav

Prague, 128 50, Czechia

Location

Helsicore - Israeli Georgian Medical Research Clinic

Tbilisi, 0112, Georgia

Location

Research Institute of Clinical Medicine

Tbilisi, 0112, Georgia

Location

The First University Clinic

Tbilisi, 0141, Georgia

Location

EVEX Hospitals - Caraps Medline

Tbilisi, 0159, Georgia

Location

Tbilisi Heart and Vascular Clinic

Tbilisi, 0159, Georgia

Location

MediClub Georgia

Tbilisi, 0160, Georgia

Location

Georgian Dutch Hospital Ltd

Tbilisi, 0172, Georgia

Location

Mtskheta Street Clinic

Tbilisi, 0179, Georgia

Location

Tbilisi Heart Center

Tbilisi, 0186, Georgia

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye, 6725, Hungary

Location

Csongrad Megyei Dr. Bugyi Istvan Korhaz

Szentes, Csongrád megye, 6600, Hungary

Location

DRC Gyogyszervizsgalo Kozpont Kft.

Székesfehérvár, Fejér, 8000, Hungary

Location

SALDINVEST Befektetesi es Vagyonkezelo Korlatolt Felelossegu Tarsasag

Székesfehérvár, Fejér, 8000, Hungary

Location

Integrity Gyogyaszati Kozpont

Zalaegerszeg, Zala County, 8900, Hungary

Location

Revita Reumatologiai Rendelo

Budapest, 1027, Hungary

Location

MÁV Kórház és Rendelőintézet Rheumatológia

Szolnok, 5000, Hungary

Location

Vital Medical Center Orvosi es Fogaszati Kozpont

Veszprém, 8200, Hungary

Location

Institutia Medico-Sanitara Publica Institutul de Cardiologie

Chisinau, 2025, Moldova

Location

Spitalul Clinic Republican

Chisinau, 2025, Moldova

Location

IMSP Spitalul Clinic Municipal Sfanta Treime

Chisinau, 2068, Moldova

Location

Instituţia Medico-Sanitară Publică Institutul de Cardiologie

Chisinau, MD 2025, Moldova

Location

Solumed Centrum Medyczne

Poznan, Greater Poland Voivodeship, 60-529, Poland

Location

Centrum Badan Klinicznych S.C.

Poznan, Greater Poland Voivodeship, 60-773, Poland

Location

Ai Centrum Medyczne

Poznan, Greater Poland Voivodeship, 61-113, Poland

Location

Centrum Medyczne HCP

Poznan, Greater Poland Voivodeship, 61-485, Poland

Location

Nasz Lekarz Osrodek Badan Klinicznych - Bydgoszcz

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-068, Poland

Location

Nasz Lekarz Przychodnie Medyczne

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Grazyna Pulka Specjalistyczny Osrodek All-med

Krakow, Lesser Poland Voivodeship, 30-033, Poland

Location

Pratia MCM Krakow

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

WroMedica

Wroclaw, Lower Silesian Voivodeship, 51-685, Poland

Location

Centrum Medyczne Oporow

Wroclaw, Lower Silesian Voivodeship, 52-416, Poland

Location

Samodzielny Publiczny Zespol Opieki Zdrowotnej w Tomaszow Lubelski

Tomaszów Lubelski, Lublin Voivodeship, 22-600, Poland

Location

Twoja Przychodnia-Centrum Medyczne Nowa Sol

Nowa Sól, Lubusz Voivodeship, 67-100, Poland

Location

RCMed Oddzial Sochaczew

Sochaczew, Masovian Voivodeship, 96-500, Poland

Location

Medycyna Kliniczna

Warsaw, Masovian Voivodeship, 00-874, Poland

Location

Rheuma Medicus Zaklad Opieki Zdrowotnej

Warsaw, Masovian Voivodeship, 02-118, Poland

Location

Ars Rheumatica - Reumatika Centrum Reumatologii

Warsaw, Masovian Voivodeship, 02-691, Poland

Location

Barwijuk Clinics

Warsaw, Masovian Voivodeship, 02-884, Poland

Location

Centrum Medyczne AMED Warszawa Targowek

Warsaw, Masovian Voivodeship, 03-291, Poland

Location

SANUS Szpital Specjalistyczny

Stalowa Wola, Podkarpackie Voivodeship, 37-450, Poland

Location

Osteo-Medic

Bialystok, Podlaskie Voivodeship, 15-351, Poland

Location

ClinicMed Daniluk Nowak Spolka Jawna

Bialystok, Podlaskie Voivodeship, 15-879, Poland

Location

Centrum Medyczne Pratia w Gdyni

Gdynia, Pomeranian Voivodeship, 81-338, Poland

Location

Silmedic w Swidniku

Katowice, Silesian Voivodeship, 40-282, Poland

Location

Ambulatorium Sp. z

Elblag, Warmian-Masurian Voivodeship, 82-300, Poland

Location

Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spolka Partnerska

Elblag, Warmian-Masurian Voivodeship, 82-300, Poland

Location

Centrum Terapii Wspolczesnej

Lodz, Łódź Voivodeship, 90-242, Poland

Location

TRIALMED CRS Piotrków Trybunalski

Piotrkow Trybunalski, Łódź Voivodeship, 97-300, Poland

Location

Clinical Rheumatological Hospital Number 25

Saint Petersburg, Sankt-Peterburg, 190068, Russia

Location

Kazan State Medical University

Kazan', Tatarstan Republic, 420103, Russia

Location

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

Yaroslavl, Yaroslavlr, 150023, Russia

Location

Chelyabinsk Regional Clinical Hospital

Chelyabinsk, 454076, Russia

Location

Medical Center Revma-Med

Kemerovo, 650070, Russia

Location

NIARMEDIK - Clinic on Clinic on Kitai Gorod

Moscow, 101000, Russia

Location

Medical Center Health Family

Novosibirsk, 630099, Russia

Location

Polyclinic of Private Security Personnel

Saint Petersburg, 192007, Russia

Location

Saratov Regional Clinical Hospital

Saratov, 410053, Russia

Location

Departmental Hospital at Smolensk Station of JSC RZhD

Smolensk, 214025, Russia

Location

Biomed

Vladimir, 600005, Russia

Location

CjSC "Center of Family Medicine"

Yekaterinburg, 620043, Russia

Location

Institute of Rheumatology

Belgrade, 11000, Serbia

Location

Institut za Lecenje i Rehabilitaciju Niška Banja

Niška Banja, 18205, Serbia

Location

Specijalna Bolnica za Reumatske bolesti Novi Sad

Novi Sad, 21112, Serbia

Location

General Hospital Djordje Jovanovic Zrenjanin

Zrenjanin, 23000, Serbia

Location

REUMEX s.r.o.

Rimavská Sobota, 979 01, Slovakia

Location

LERAM s.r.o.

Topoľčany, 95501, Slovakia

Location

ALBAMED s.r.o.

Zvolen, 960 01, Slovakia

Location

Related Publications (1)

• 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.

  PMID: 38316489 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

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: Clinical Development
• Organization: Fresenius Kabi SwissBioSim GmbH

clinical.development@fresenius-kabi.com

793075735

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: August 11, 2020
• First Posted: August 13, 2020
• Study Start: August 3, 2020
• Primary Completion: August 31, 2021
• Study Completion: June 6, 2022
• Last Updated: June 27, 2023
• Results First Posted: October 24, 2022

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

GE (9); SE (4); MO (4); CZ (8); HU (8); PL (27); RU (12); SL (3); BU (10)