MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04512001
• Other study ID #: FKS456-001
• Secondary ID: 2019-004369-42
• Status: Completed
• Phase: Phase 3
• Start date: August 3, 2020
• Est. completion date: June 6, 2022

Study information

• Verified date: June 2023
• Source: Fresenius Kabi SwissBioSim GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 604
• Est. completion date: June 6, 2022
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• MSB11456
Participants will receive MSB11456 subcutaneously, once a week.
• EU-approved RoActemra
Participants will receive EU-approved RoActemra® subcutaneously, once a week.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Fresenius Kabi SwissBioSim GmbH

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Georgia,  Hungary,  Moldova, Republic of,  Poland,  Russian Federation,  Serbia,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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*v(TJC28) + 0.28*v(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	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*v(TJC28) + 0.28*v(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.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16; Extended Period Baseline (Week 24), Week 30, Week 42, and Week 52
Secondary	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	Baseline; Week 24
Secondary	Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE)		Baseline to end of study, up to Week 63
Secondary	Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE)		Baseline to end of study, up to Week 63
Secondary	Percentage of Participants With Positive Anti-Drug Antibodies (ADAs)		Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Secondary	Anti-Drug Antibodies (ADAs) Titer Levels		Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Secondary	Percentage of Participants With Neutralizing Antibodies (NAb)		Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55