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Rheumatoid ArthritisPhase 3NCT04512001

MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis

A Phase 3 study testing MSB11456 and EU-approved RoActemra in people with Rheumatoid Arthritis, run by Fresenius Kabi SwissBioSim GmbH at 85 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
MSB11456 and EU-approved RoActemra
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
604 participants
Where
85 sitesin 9 countries
Study dates
3 Aug 2020to 6 Jun 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.
  • 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.

Trial locations and contacts

85 sites in 9 countries.

85 sites in 9 countries

Poland27 sites

  • Osteo-Medic

    Bialystok, Podlaskie Voivodeship, 15-351

  • ClinicMed Daniluk Nowak Spolka Jawna

    Bialystok, Podlaskie Voivodeship, 15-879

  • Nasz Lekarz Osrodek Badan Klinicznych - Bydgoszcz

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-068

  • Ambulatorium Sp. z

    Elblag, Warmian-Masurian Voivodeship, 82-300

  • Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spolka Partnerska

    Elblag, Warmian-Masurian Voivodeship, 82-300

  • Centrum Medyczne Pratia w Gdyni

    Gdynia, Pomeranian Voivodeship, 81-338

  • Silmedic w Swidniku

    Katowice, Silesian Voivodeship, 40-282

  • Grazyna Pulka Specjalistyczny Osrodek All-med

    Krakow, Lesser Poland Voivodeship, 30-033

  • Pratia MCM Krakow

    Krakow, Lesser Poland Voivodeship, 30-510

  • Centrum Terapii Wspolczesnej

    Lodz, Łódź Voivodeship, 90-242

  • Twoja Przychodnia-Centrum Medyczne Nowa Sol

    Nowa Sól, Lubusz Voivodeship, 67-100

  • TRIALMED CRS Piotrków Trybunalski

    Piotrkow Trybunalski, Łódź Voivodeship, 97-300

  • Solumed Centrum Medyczne

    Poznan, Greater Poland Voivodeship, 60-529

  • Centrum Badan Klinicznych S.C.

    Poznan, Greater Poland Voivodeship, 60-773

  • Ai Centrum Medyczne

    Poznan, Greater Poland Voivodeship, 61-113

  • Centrum Medyczne HCP

    Poznan, Greater Poland Voivodeship, 61-485

  • RCMed Oddzial Sochaczew

    Sochaczew, Masovian Voivodeship, 96-500

  • SANUS Szpital Specjalistyczny

    Stalowa Wola, Podkarpackie Voivodeship, 37-450

  • Samodzielny Publiczny Zespol Opieki Zdrowotnej w Tomaszow Lubelski

    Tomaszów Lubelski, Lublin Voivodeship, 22-600

  • Nasz Lekarz Przychodnie Medyczne

    Torun, Kuyavian-Pomeranian Voivodeship, 87-100

  • Medycyna Kliniczna

    Warsaw, Masovian Voivodeship, 00-874

  • Rheuma Medicus Zaklad Opieki Zdrowotnej

    Warsaw, Masovian Voivodeship, 02-118

  • Ars Rheumatica - Reumatika Centrum Reumatologii

    Warsaw, Masovian Voivodeship, 02-691

  • Barwijuk Clinics

    Warsaw, Masovian Voivodeship, 02-884

  • Centrum Medyczne AMED Warszawa Targowek

    Warsaw, Masovian Voivodeship, 03-291

  • WroMedica

    Wroclaw, Lower Silesian Voivodeship, 51-685

  • Centrum Medyczne Oporow

    Wroclaw, Lower Silesian Voivodeship, 52-416

Other trials in Poland

Russia12 sites

  • Chelyabinsk Regional Clinical Hospital

    Chelyabinsk, 454076

  • Kazan State Medical University

    Kazan', Tatarstan Republic, 420103

  • Medical Center Revma-Med

    Kemerovo, 650070

  • NIARMEDIK - Clinic on Clinic on Kitai Gorod

    Moscow, 101000

  • Medical Center Health Family

    Novosibirsk, 630099

  • Clinical Rheumatological Hospital Number 25

    Saint Petersburg, Sankt-Peterburg, 190068

  • Polyclinic of Private Security Personnel

    Saint Petersburg, 192007

  • Saratov Regional Clinical Hospital

    Saratov, 410053

  • Departmental Hospital at Smolensk Station of JSC RZhD

    Smolensk, 214025

  • Biomed

    Vladimir, 600005

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

    Yaroslavl, Yaroslavlr, 150023

  • CjSC "Center of Family Medicine"

    Yekaterinburg, 620043

Other trials in Russia

Bulgaria10 sites

  • Medical Center Hipokrat 2000 OOD

    Haskovo, Haskovo, 6300

  • Medical Center MedConsult Pleven

    Pleven, 5800

  • University Multiprofile Hospital for Active Treatment Pulmed

    Plovdiv, 4002

  • Multiprofile Hospital for Active Treatment Plovdiv

    Plovdiv, 4003

  • Medical Center Teodora

    Rousse, 7012

  • MHAT "Lyulin" EAD

    Sofia, Sofia, 1336

  • Military Medical Academy - Sofia

    Sofia, Sofia, 1606

  • Medical Center N.I.Pirogov EOOD

    Sofia, Sofia, 1612

  • Diagnostic and Consultative Center Equita

    Varna, 9002

  • MC Sanador M

    Vidin, 3703

Other trials in Bulgaria

Georgia9 sites

  • Helsicore - Israeli Georgian Medical Research Clinic

    Tbilisi, 0112

  • Research Institute of Clinical Medicine

    Tbilisi, 0112

  • The First University Clinic

    Tbilisi, 0141

  • EVEX Hospitals - Caraps Medline

    Tbilisi, 0159

  • Tbilisi Heart and Vascular Clinic

    Tbilisi, 0159

  • MediClub Georgia

    Tbilisi, 0160

  • Georgian Dutch Hospital Ltd

    Tbilisi, 0172

  • Mtskheta Street Clinic

    Tbilisi, 0179

  • Tbilisi Heart Center

    Tbilisi, 0186

Other trials in Georgia

Czechia8 sites

  • Revmatologie, s.r.o.

    Brno, Jihormoravsky KRAJ, 638 00

  • CCR Ostrava

    Ostrava, Severomoravsky KRAJ, 702 00

  • Revmatologie MUDr. Klára Šírová s.r.o.

    Ostrava, Severomoravsky KRAJ, 702 00

  • Vesalion s.r.o.

    Ostrava, 702 00

  • Revmatologie MUDr. Zuzana Urbanova

    Prague, Prague, 140 00

  • Revmatologicky Ustav

    Prague, 128 50

  • Medical Plus

    Uherské Hradiště, Jihormoravsky KRAJ, 686 01

  • PV-Medical Services, s.r.o.

    Zlín, Severomoravsky KRAJ, 760 01

Other trials in Czechia

Hungary8 sites

  • Revita Reumatologiai Rendelo

    Budapest, 1027

  • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

    Szeged, Csongrád megye, 6725

  • DRC Gyogyszervizsgalo Kozpont Kft.

    Székesfehérvár, Fejér, 8000

  • SALDINVEST Befektetesi es Vagyonkezelo Korlatolt Felelossegu Tarsasag

    Székesfehérvár, Fejér, 8000

  • Csongrad Megyei Dr. Bugyi Istvan Korhaz

    Szentes, Csongrád megye, 6600

  • MÁV Kórház és Rendelőintézet Rheumatológia

    Szolnok, 5000

  • Vital Medical Center Orvosi es Fogaszati Kozpont

    Veszprém, 8200

  • Integrity Gyogyaszati Kozpont

    Zalaegerszeg, Zala County, 8900

Other trials in Hungary

Moldova4 sites

  • Institutia Medico-Sanitara Publica Institutul de Cardiologie

    Chisinau, 2025

  • Spitalul Clinic Republican

    Chisinau, 2025

  • IMSP Spitalul Clinic Municipal Sfanta Treime

    Chisinau, 2068

  • Instituţia Medico-Sanitară Publică Institutul de Cardiologie

    Chisinau, MD 2025

Other trials in Moldova

Serbia4 sites

  • Institute of Rheumatology

    Belgrade, 11000

  • Institut za Lecenje i Rehabilitaciju Niška Banja

    Niška Banja, 18205

  • Specijalna Bolnica za Reumatske bolesti Novi Sad

    Novi Sad, 21112

  • General Hospital Djordje Jovanovic Zrenjanin

    Zrenjanin, 23000

Other trials in Serbia

Slovakia3 sites

  • REUMEX s.r.o.

    Rimavská Sobota, 979 01

  • LERAM s.r.o.

    Topoľčany, 95501

  • ALBAMED s.r.o.

    Zvolen, 960 01

Other trials in Slovakia

About this study

Official title: A Randomized, Double-Blind, Multiple-Dose, Parallel-Group, Two-Arm Study to Evaluate the Efficacy, Safety and Immunogenicity of MSB11456 Compared to European Union-approved RoActemra® in Patients With Moderately to Severely Active Rheumatoid Arthritis (APTURA I Study)

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.

Being tested
MSB11456, EU-approved RoActemra
Keywords
MSB11456, RoActemra®
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MSB11456Drug

    Participants will receive MSB11456 subcutaneously, once a week.

  • EU-approved RoActemraDrug

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

Study groups in NCT04512001
Study groupRoleWhat they receive
MSB11456ExperimentalNot described
Receives: Drug: MSB11456
RoActemra®Active comparatorNot described
Receives: Drug: EU-approved RoActemra

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline; Week 24

Secondary outcomes (7)

  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: 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.

    Measured: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16; Extended Period Baseline (Week 24), Week 30, Week 42, and Week 52

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

    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

    Measured: Baseline; Week 24

  3. Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE)

    Measured: Baseline to end of study, up to Week 63

  4. Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE)

    Measured: Baseline to end of study, up to Week 63

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

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

  6. Anti-Drug Antibodies (ADAs) Titer Levels

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

  7. Percentage of Participants With Neutralizing Antibodies (NAb)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2020
  2. Study start3 Aug 2020
  3. Primary completion31 Aug 2021
  4. Study completion6 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
604 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04512001
Sponsor's protocol ID
FKS456-001
Other IDs
2019-004369-42, 2019
Status last verified
Jun 2023
First submitted
11 Aug 2020
Last updated
27 Jun 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38316489

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MSB11456 and EU-approved RoActemra in people with Rheumatoid Arthritis, run by Fresenius Kabi SwissBioSim GmbH at 85 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 85 sites in Poland, Russia, Bulgaria, Georgia, Czechia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) (time frame: Baseline; Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04512001, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2023.

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