MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis

• Sponsor: Fresenius Kabi SwissBioSim GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04512001
• Collaborator: (none)
• Enrollment: 542
• Locations: 82
• Arms: 2
• Actual Duration (Months): 22.3
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: MSB11456; Drug: EU-approved RoActemra	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 542 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Jul 27, 2020
• Actual Primary Completion Date: Oct 11, 2021
• Actual Study Completion Date: Jun 6, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MSB11456	Drug: MSB11456; Participants will receive MSB11456 subcutaneously, once a week.
Active Comparator: RoActemra®	Drug: EU-approved RoActemra; Participants will receive EU-approved RoActemra® subcutaneously, once a week.

Outcome Measures

Primary Outcome Measures

1. Change from Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) [Baseline; Week 24]

Secondary Outcome Measures

1. Change from Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) [Baseline; Week 52]

2. Number of Participants with 20% Improvement in American College of Rheumatology (ACR20) Response [Week 24]

3. Number of Participants who Experienced One or More Treatment-Emergent Adverse Event (TEAE) [Baseline to end of study, up to Week 63]

4. Number of Participants who Experienced One or More Serious Adverse Event (SAE) [Baseline to end of study, up to Week 63]

5. Number of Participants with Positive Anti-Drug Antibodies (ADAs) [Week 2; Week 55]

6. Anti-Drug Antibodies (ADAs) Titer Levels [Week 2; Week 55]

7. Number of Participants with Confirmed Neutralizing Antibodies (NAb) [Week 2; Week 55]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Center Hipokrat 2000 OOD	Haskovo	Khaskovo	Bulgaria	6300
2	MHAT "Lyulin" EAD	Sofia	Sofiya	Bulgaria	1336
3	Military Medical Academy - Sofia	Sofia	Sofiya	Bulgaria	1606
4	Medical Center N.I.Pirogov EOOD	Sofia	Sofiya	Bulgaria	1612
5	Medical Center MedConsult Pleven	Pleven		Bulgaria	5800
6	University Multiprofile Hospital for Active Treatment Pulmed	Plovdiv		Bulgaria	4002
7	Multiprofile Hospital for Active Treatment Plovdiv	Plovdiv		Bulgaria	4003
8	Medical Center Teodora	Ruse		Bulgaria	7012
9	Diagnostic and Consultative Center Equita	Varna		Bulgaria	9002
10	MC Sanador M	Vidin		Bulgaria	3703
11	Revmatologie, s.r.o.	Brno	Jihormoravsky KRAJ	Czechia	638 00
12	Medical Plus	Uherské Hradiště	Jihormoravsky KRAJ	Czechia	686 01
13	Revmatologie MUDr. Zuzana Urbanova	Praha 4	Praha	Czechia	140 00
14	CCR Ostrava	Ostrava	Severomoravsky KRAJ	Czechia	702 00
15	Revmatologie MUDr. Klára Šírová s.r.o.	Ostrava	Severomoravsky KRAJ	Czechia	702 00
16	PV-Medical Services, s.r.o.	Zlin	Severomoravsky KRAJ	Czechia	760 01
17	Vesalion s.r.o.	Ostrava		Czechia	702 00
18	Revmatologicky Ustav	Praha		Czechia	128 50
19	Helsicore - Israeli Georgian Medical Research Clinic	Tbilisi		Georgia	0112
20	Research Institute of Clinical Medicine	Tbilisi		Georgia	0112
21	The First University Clinic	Tbilisi		Georgia	0141
22	EVEX Hospitals - Caraps Medline	Tbilisi		Georgia	0159
23	Tbilisi Heart and Vascular Clinic	Tbilisi		Georgia	0159
24	MediClub Georgia	Tbilisi		Georgia	0160
25	Georgian Dutch Hospital Ltd	Tbilisi		Georgia	0172
26	Mtskheta Street Clinic	Tbilisi		Georgia	0179
27	Tbilisi Heart Center	Tbilisi		Georgia	0186
28	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged	Csongrad	Hungary	6725
29	Csongrad Megyei Dr. Bugyi Istvan Korhaz	Szentes	Csongrad	Hungary	6600
30	DRC Gyogyszervizsgalo Kozpont Kft.	Szekesfehervar	Fejer	Hungary	8000
31	SALDINVEST Befektetesi es Vagyonkezelo Korlatolt Felelossegu Tarsasag	Szekesfehervar	Fejer	Hungary	8000
32	Integrity Gyogyaszati Kozpont	Zalaegerszeg	Zala	Hungary	8900
33	Revita Reumatologiai Rendelo	Budapest		Hungary	1027
34	Vital Medical Center Orvosi es Fogaszati Kozpont	Veszprem		Hungary	8200
35	Institutia Medico-Sanitara Publica Institutul de Cardiologie	Chisinau		Moldova, Republic of	2025
36	Spitalul Clinic Republican	Chisinau		Moldova, Republic of	2025
37	IMSP Spitalul Clinic Municipal Sfanta Treime	Chisinau		Moldova, Republic of	2068
38	Instituţia Medico-Sanitară Publică Institutul de Cardiologie	Chisinau		Moldova, Republic of	MD 2025
39	WroMedica	Wroclaw	Dolnoslaskie	Poland	51-685
40	Centrum Medyczne Oporow	Wroclaw	Dolnoslaskie	Poland	52-416
41	Nasz Lekarz Osrodek Badan Klinicznych - Bydgoszcz	Bydgoszcz	Kujawsko-pomorskie	Poland	85-068
42	Nasz Lekarz Przychodnie Medyczne	Torun	Kujawsko-pomorskie	Poland	87-100
43	Centrum Terapii Wspolczesnej	Lodz	Lodzkie	Poland	90-242
44	Samodzielny Publiczny Zespol Opieki Zdrowotnej w Tomaszow Lubelski	Tomaszow Lubelski	Lubelskie	Poland	22-600
45	Twoja Przychodnia-Centrum Medyczne Nowa Sol	Nowa Sol	Lubuskie	Poland	67-100
46	Grazyna Pulka Specjalistyczny Osrodek All-med	Krakow	Malopolskie	Poland	30-033
47	Pratia MCM Krakow	Krakow	Malopolskie	Poland	30-510
48	RCMed Oddzial Sochaczew	Sochaczew	Mazowieckie	Poland	96-500
49	Medycyna Kliniczna	Warszawa	Mazowieckie	Poland	00-874
50	Rheuma Medicus Zaklad Opieki Zdrowotnej	Warszawa	Mazowieckie	Poland	02-118
51	Ars Rheumatica - Reumatika Centrum Reumatologii	Warszawa	Mazowieckie	Poland	02-691
52	Barwijuk Clinics	Warszawa	Mazowieckie	Poland	02-884
53	Centrum Medyczne AMED Warszawa Targowek	Warszawa	Mazowieckie	Poland	03-291
54	SANUS Szpital Specjalistyczny	Stalowa Wola	Podkarpackie	Poland	37-450
55	Osteo-Medic	Bialystok	Podlaskie	Poland	15-351
56	ClinicMed Daniluk Nowak Spolka Jawna	Bialystok	Podlaskie	Poland	15-879
57	Centrum Medyczne Pratia w Gdyni	Gdynia	Pomorskie	Poland	81-338
58	Silmedic w Swidniku	Katowice	Slaskie	Poland	40-282
59	Ambulatorium Barbara Bazela	Elblag	Warminsko-mazurskie	Poland	82-300
60	Centrum Kliniczno Badawcze J Brzezicki B Gornikiewicz Brzezicka Lekarze Spolka Partnerska	Elblag	Warminsko-mazurskie	Poland	82-300
61	Solumed Centrum Medyczne	Poznan	Wielkopolskie	Poland	60-529
62	Centrum Badan Klinicznych S.C.	Poznan	Wielkopolskie	Poland	60-773
63	Ai Centrum Medyczne	Poznan	Wielkopolskie	Poland	61-113
64	Centrum Medyczne HCP	Poznan	Wielkopolskie	Poland	61-485
65	Clinical Rheumatological Hospital Number 25	Saint-Petersburg	Saint Petersburg	Russian Federation	190068
66	Kazan State Medical University	Kazan	Tatarstan	Russian Federation	420103
67	State Budgetary Healthcare Institution of the Yaroslavl Region Clinical Hospital No. 2	Yaroslavl	Yaroslavlr	Russian Federation	150023
68	Chelyabinsk Regional Clinical Hospital	Chelyabinsk		Russian Federation	454076
69	CjSC "Center of Family Medicine"	Ekaterinburg		Russian Federation	620043
70	Medical Center Revma-Med	Kemerovo		Russian Federation	650070
71	NIARMEDIK - Clinic on Clinic on Kitai Gorod	Moscow		Russian Federation	101000
72	Medical Center Health Family	Novosibirsk		Russian Federation	630099
73	Polyclinic of Private Security Personnel	Saint Petersburg		Russian Federation	192007
74	Saratov Regional Clinical Hospital	Saratov		Russian Federation	410053
75	Departmental Hospital at Smolensk Station of JSC RZhD	Smolensk		Russian Federation	214025
76	Biomed	Vladimir		Russian Federation	600005
77	Institute of Rheumatology	Belgrade		Serbia	11000
78	Institut za Lecenje i Rehabilitaciju Niška Banja	Niška Banja		Serbia	18205
79	Specijalna Bolnica za Reumatske bolesti Novi Sad	Novi Sad		Serbia	21112
80	REUMEX s.r.o.	Rimavska Sobota		Slovakia	979 01
81	LERAM s.r.o.	Topolcany		Slovakia	95501
82	ALBAMED s.r.o.	Zvolen		Slovakia	960 01

Sponsors and Collaborators

• Fresenius Kabi SwissBioSim GmbH

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fresenius Kabi SwissBioSim GmbH
• ClinicalTrials.gov Identifier: NCT04512001
• Other Study ID Numbers: FKS456-001; 2019-004369-42
• First Posted: Aug 13, 2020
• Last Update Posted: Jun 22, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Fresenius Kabi SwissBioSim GmbH: MSB11456; RoActemra®
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

No Results Posted as of Jun 22, 2022