A study of MSB11456 compared to RoActemra in patients with moderately to severely active rheumatoid arthritis (APTURA I)

Phase 1

Conditions: Moderately to severely active Rheumatoid Arthritis
MedDRA version: 23.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2019-004369-42-CZ

Lead Sponsor: Fresenius Kabi SwissBioSim GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 542

Inclusion Criteria

1. Are =18 years of age.
2. Diagnosis of rheumatoid arthritis according to the revised 1987 ACR/EULAR
Classification 2010 criteria with disease duration of =6 months.
3. Have moderately to severely active rheumatoid arthritis as defined by: a.Swollen Joint Count =6
(66 joint count) and Tender Joint Count =6 (68 joint count)
4. 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.
5. Have had previous inadequate clinical response to at least one modifying anti rheumatic drug.
6. 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.
Note: A separate ICF will be provided to and signed by each patient to
provide information on the general risks of study participation related to
COVID-19 and to document that it is understood by the patient. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 298
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 244

Exclusion Criteria

1. American College of Rheumatology functional class IV as defined by
the ACR classification of functional status or wheelchair/bedbound.
2. Rheumatic autoimmune disease or history of/current inflammatory joint disease other than rheumatoid arthritis or significant systemic involvement secondary to rheumatoid arthritis. Sjögren's syndrome
secondary to rheumatoid arthritis is allowed.
3. Previously received tocilizumab, an investigational or licensed biosimilar of tocilizumab or any interleukin-6 acting drugs (approved or investigational).
4. Prior use of targeted synthetic disease-modifying anti-rheumatic drugs like janus kinase inhibitors
5. Prior use of any biological agent for a condition other than rheumatoid arthritis (e.g., ranibizumab, denosumab).
6. Prior use of more than two biologic treatments for rheumatoid arthritis.
7. Prior use of biologic investigational drugs (excluding biosimilars) for the treatment of rheumatoid arthritis.
8. Received any investigational drugs within 12 weeks or five drug half lives prior to screening or planned intake of an investigational drug during the course of this trial including the Follow-Up Period.
9. Previous treatment with any alkylating agents or cell-depleting therapies including investigational drugs or approved biosimilars, or has previously undergone total lymphoid irradiation.
10. Use of non-steroidal anti-inflammatory drugs not at a stable dose for at least 4 weeks prior to randomization or exceeding the maximum recommended dose. Note: Patients are permitted to take aspirin at a dose of =325 mg daily for cardiac prophylaxis.
11. Use of oral corticosteroids >10 mg/day prednisone or equivalent if the dose has not been stable for at least 6 weeks prior to randomization.
12. Intra-articular or parenteral corticosteroids within 4 weeks prior to randomization.
13. Use of high potency opioid analgesics
14. Has been treated with intravenous gamma globulin or plasmapheresis within 6 months of randomization.
15. Received a live or attenuated vaccine within 4 weeks prior to randomization.
16. History of hypersensitivity or severe allergic reactions to monoclonal antibodies, any components of the study drug formulations,
comparable drugs, or latex.
17. Patient is considered by the Investigator, for any reason, to be an unsuitable candidate for the study. Investigator should specifically
evaluate the patient's eligibility taking into consideration COVID-19 risk factors and situation.
18. Has a serious and/or unstable and/or poorly controlled medical condition that, in the opinion of the Investigator, would put the patient at risk by participation in the study.
19. History of diverticulosis requiring antibiotic treatment or any other GI condition that might predispose the patient to gastrointestinal
perforations.
20. Uncontrolled medical conditions for which flares are commonly treated with corticosteroids or systemic corticosteroid treatment for
these conditions within the last 12 months prior to randomization.
21. Major surgery within 8 weeks prior to screening or planned major surgery during the study.
22. History of, or current myeloproliferative or lymphoproliferative disease or malignancy.
23. Medical evidence of current or history of primary or secondary immunodeficiency as per Investigator's judgment.
24. Pre-existing or recent-onset central or peripheral nervous system demyelinating disorder, or symptoms suggestive of such a disorder as per Investigator's judgment.
25. Confirmed or, base

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to demonstrate equivalent efficacy of proposed biosimilar tocilizumab MSB11456 and EU-approved RoActemra both administered subcutaneously to patients with moderately to severely active rheumatoid arthritis.;Secondary Objective: To compare the safety, immunogenicity and long-term efficacy of MSB11456 to EU-approved RoActemra.;Primary end point(s): The primary efficacy endpoint is the mean absolute change from baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24.;Timepoint(s) of evaluation of this end point: From baseline to Week 24.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy:<br>- DAS28-ESR mean absolute change from baseline at all assessment<br>visits (except Week 1)<br>- ACR20 (20% improvement in ACR Core Set Measurements) response<br>rate at Week 24.<br>Safety:<br>- Occurrence of treatment-emergent adverse events<br>- Occurrence of serious adverse events<br>Immunogenicity:<br>- Antidrug antibody incidence<br>- Antidrug antibody titer<br>- Neutralizing antibody incidence;Timepoint(s) of evaluation of this end point: DAS28-ESR mean absolute change from baseline at all assessment visits<br>excl. Week 1 and 24.<br>ACR20 response rate at Week 24.<br>Occurrence of treatment-emergent AEs up to Week 24, Week 30, Week<br>55 and Week 63.<br>Occurrence of SAEs up to Week 24, Week 30, Week 55 and Week 63.<br>Antidrug antibody incidence at Weeks 2, 12, 24, 30, 52 and 55.<br>Antidrug antibody titer at Weeks 2, 12, 24, 30, 52 and 55.<br>Neutralizing antibody incidence at Weeks 2, 12, 24, 30, 52 and 55.

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