Clinical trial NCT04512001: MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: MSB11456
RoActemra®
Lead sponsor: Fresenius Kabi SwissBioSim GmbH
Sponsor class: INDUSTRY
First posted: 2020-08-13
Enrollment: 604
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16; Extended Period Baseline (Week 24), Week 30, Week 42, and Week 52
measure: Number of Participants With 20% Improvement in American College of Rheumatology (ACR20) Response
timeFrame: Baseline; Week 24
measure: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE)
timeFrame: Baseline to end of study, up to Week 63
measure: Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE)
timeFrame: Baseline to end of study, up to Week 63
measure: Percentage of Participants With Positive Anti-Drug Antibodies (ADAs)
timeFrame: Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
measure: Anti-Drug Antibodies (ADAs) Titer Levels
timeFrame: Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
measure: Percentage of Participants With Neutralizing Antibodies (NAb)
timeFrame: Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Other outcomes:
Locations:
city: Haskovo
country: Bulgaria
facility: Medical Center Hipokrat 2000 OOD
state: Khaskovo
city: Sofia
country: Bulgaria
facility: MHAT "Lyulin" EAD
state: Sofiya
city: Sofia
country: Bulgaria
facility: Military Medical Academy - Sofia
state: Sofiya
city: Sofia
country: Bulgaria
facility: Medical Center N.I.Pirogov EOOD
state: Sofiya
city: Pleven
country: Bulgaria
facility: Medical Center MedConsult Pleven
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Pulmed
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Plovdiv
city: Ruse
country: Bulgaria
facility: Medical Center Teodora
city: Varna
country: Bulgaria
facility: Diagnostic and Consultative Center Equita
city: Vidin
country: Bulgaria
facility: MC Sanador M
city: Brno
country: Czechia
facility: Revmatologie, s.r.o.
state: Jihormoravsky KRAJ
city: Uherské Hradiště
country: Czechia
facility: Medical Plus
state: Jihormoravsky KRAJ
city: Praha 4
country: Czechia
facility: Revmatologie MUDr. Zuzana Urbanova
state: Praha
city: Ostrava
country: Czechia
facility: CCR Ostrava
state: Severomoravsky KRAJ
city: Ostrava
country: Czechia
facility: Revmatologie MUDr. Klára Šírová s.r.o.
state: Severomoravsky KRAJ
city: Zlin
country: Czechia
facility: PV-Medical Services, s.r.o.
state: Severomoravsky KRAJ
city: Ostrava
country: Czechia
facility: Vesalion s.r.o.
city: Praha
country: Czechia
facility: Revmatologicky Ustav
city: Tbilisi
country: Georgia
facility: Helsicore - Israeli Georgian Medical Research Clinic
city: Tbilisi
country: Georgia
facility: Research Institute of Clinical Medicine
city: Tbilisi
country: Georgia
facility: The First University Clinic
city: Tbilisi
country: Georgia
facility: EVEX Hospitals - Caraps Medline
city: Tbilisi
country: Georgia
facility: Tbilisi Heart and Vascular Clinic
city: Tbilisi
country: Georgia
facility: MediClub Georgia
city: Tbilisi
country: Georgia
facility: Georgian Dutch Hospital Ltd
city: Tbilisi
country: Georgia
facility: Mtskheta Street Clinic
city: Tbilisi
country: Georgia
facility: Tbilisi Heart Center
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
state: Csongrad
city: Szentes
country: Hungary
facility: Csongrad Megyei Dr. Bugyi Istvan Korhaz
state: Csongrad
city: Szekesfehervar
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft.
state: Fejer
city: Szekesfehervar
country: Hungary
facility: SALDINVEST Befektetesi es Vagyonkezelo Korlatolt Felelossegu Tarsasag
state: Fejer
city: Zalaegerszeg
country: Hungary
facility: Integrity Gyogyaszati Kozpont
state: Zala
city: Budapest
country: Hungary
facility: Revita Reumatologiai Rendelo
city: Szolnok
country: Hungary
facility: MÁV Kórház és Rendelőintézet Rheumatológia
city: Veszprem
country: Hungary
facility: Vital Medical Center Orvosi es Fogaszati Kozpont
city: Chisinau
country: Moldova, Republic of
facility: Institutia Medico-Sanitara Publica Institutul de Cardiologie
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clinic Republican
city: Chisinau
country: Moldova, Republic of
facility: IMSP Spitalul Clinic Municipal Sfanta Treime
city: Chisinau
country: Moldova, Republic of
facility: Instituţia Medico-Sanitară Publică Institutul de Cardiologie
city: Wroclaw
country: Poland
facility: WroMedica
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Centrum Medyczne Oporow
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych - Bydgoszcz
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej
state: Lodzkie
city: Piotrków Trybunalski
country: Poland
facility: TRIALMED CRS Piotrków Trybunalski
state: Lodzkie
city: Tomaszow Lubelski
country: Poland
facility: Samodzielny Publiczny Zespol Opieki Zdrowotnej w Tomaszow Lubelski
state: Lubelskie
city: Nowa Sol
country: Poland
facility: Twoja Przychodnia-Centrum Medyczne Nowa Sol
state: Lubuskie
city: Krakow
country: Poland
facility: Grazyna Pulka Specjalistyczny Osrodek All-med
state: Malopolskie
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Malopolskie
city: Sochaczew
country: Poland
facility: RCMed Oddzial Sochaczew
state: Mazowieckie
city: Warszawa
country: Poland
facility: Medycyna Kliniczna
state: Mazowieckie
city: Warszawa
country: Poland
facility: Rheuma Medicus Zaklad Opieki Zdrowotnej
state: Mazowieckie
city: Warszawa
country: Poland
facility: Ars Rheumatica - Reumatika Centrum Reumatologii
state: Mazowieckie
city: Warszawa
country: Poland
facility: Barwijuk Clinics
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED Warszawa Targowek
state: Mazowieckie
city: Stalowa Wola
country: Poland
facility: SANUS Szpital Specjalistyczny
state: Podkarpackie
city: Bialystok
country: Poland
facility: Osteo-Medic
state: Podlaskie
city: Bialystok
country: Poland
facility: ClinicMed Daniluk Nowak Spolka Jawna
state: Podlaskie
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia w Gdyni
state: Pomorskie
city: Katowice
country: Poland
facility: Silmedic w Swidniku
state: Slaskie
city: Elblag
country: Poland
facility: Ambulatorium Sp. z
state: Warminsko-mazurskie
city: Elblag
country: Poland
facility: Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spolka Partnerska
state: Warminsko-mazurskie
city: Poznan
country: Poland
facility: Solumed Centrum Medyczne
state: Wielkopolskie
city: Poznan
country: Poland
facility: Centrum Badan Klinicznych S.C.
state: Wielkopolskie
city: Poznan
country: Poland
facility: Ai Centrum Medyczne
state: Wielkopolskie
city: Poznan
country: Poland
facility: Centrum Medyczne HCP
state: Wielkopolskie
city: Saint-Petersburg
country: Russian Federation
facility: Clinical Rheumatological Hospital Number 25
state: Saint Petersburg
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
state: Tatarstan
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Yaroslavl Region Clinical Hospital No. 2
state: Yaroslavlr
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Hospital
city: Ekaterinburg
country: Russian Federation
facility: CjSC "Center of Family Medicine"
city: Kemerovo
country: Russian Federation
facility: Medical Center Revma-Med
city: Moscow
country: Russian Federation
facility: NIARMEDIK - Clinic on Clinic on Kitai Gorod
city: Novosibirsk
country: Russian Federation
facility: Medical Center Health Family
city: Saint Petersburg
country: Russian Federation
facility: Polyclinic of Private Security Personnel
city: Saratov
country: Russian Federation
facility: Saratov Regional Clinical Hospital
city: Smolensk
country: Russian Federation
facility: Departmental Hospital at Smolensk Station of JSC RZhD
city: Vladimir
country: Russian Federation
facility: Biomed
city: Belgrade
country: Serbia
facility: Institute of Rheumatology
city: Niška Banja
country: Serbia
facility: Institut za Lecenje i Rehabilitaciju Niška Banja
city: Novi Sad
country: Serbia
facility: Specijalna Bolnica za Reumatske bolesti Novi Sad
city: Zrenjanin
country: Serbia
facility: General Hospital Djordje Jovanovic Zrenjanin
city: Rimavska Sobota
country: Slovakia
facility: REUMEX s.r.o.
city: Topolcany
country: Slovakia
facility: LERAM s.r.o.
city: Zvolen
country: Slovakia
facility: ALBAMED s.r.o.
Study officials:
References: