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: 21.0Level: 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-HU
• Lead Sponsor: Fresenius Kabi SwissBioSim GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-03
• Last Update Posted: 2 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 542

Inclusion Criteria

1. Are =18 years of age.
2. Have a body weight of <100 kg at screening.
3. Diagnosis of rheumatoid arthritis according to the revised 1987 ACR/EULAR Classification 2010 criteria with disease duration of =6 months prior to the Screening Visit.
4. 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) at screening and randomization.
b. Radiographic evidence of =1 joint with a definite erosion attributable to rheumatoid arthritis at screening. The radiographic evidence of joint erosion should be no older than 6 months.
c. C-reactive protein =1 mg/dL (=10 mg/L) and/or erythrocyte sedimentation rate =28 mm/hour at screening.
5. 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. Note: Oral and/or subcutaneous administration of methotrexate is allowed.
6. Must be willing to receive at least 5 mg/week or equivalent of folic acid.
7. Have had previous inadequate clinical response to at least one modifying anti rheumatic drug.
8. Have withdrawn all disease-modifying anti-rheumatic drugs other than methotrexate at least 8 weeks prior to randomization with the exception of leflunomide which must have been discontinued for =12 weeks prior to randomization (or =4 weeks after 11 days of standard cholestyramine washout).
9. Had discontinued biologic treatment for =12 weeks prior to randomization.
10. Must be able and willing to self-administer subcutaneous injections or have a qualified/trained person(s) available to administer subcutaneous injections.
11. 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.
Women of childbearing potential whose preferred lifestyle is total abstinence from intercourse may participate in the study.
Withdrawal and rhythm methods are not considered to be highly effective methods of contraception and are not permitted as the sole method of contraception in this study.
12. Women who are postmenopausal (i.e., age-related amenorrhea =12 consecutive months and increased follicle-stimulating hormone >40 mIU/mL), or women who have undergone documented hysterectomy, bilateral oophorectomy, or bilateral salpingectomy are exempt from pregnancy testing. If necessary to confirm postmenopausal status, a follicle-stimulating hormone sample will be tested at screening.
Females on hormone replacement therapy and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their hormone replacement therapy during the study. Otherwise, they must discontinue hormone replacement therapy to allow confirmation of postmenopausal status before study enrollment. Women who were taking hormone replacement therapy prior to study entry are allowed to participate in t

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.
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.
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 (whichever is longer) 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. Use of paracetamol is allowed in the study.
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 such as but not limited to poorly controlled diabetes, unstable ischemic heart disease, uncontrolled hypertension (systolic =160 mmHg and/or diastolic =95 mmHg) or other cardiovascular, cerebrovascular, gastrointestinal, hepatic, renal, hematological (including pancytopenia, aplastic anemia, or blood dyscrasia), 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 patient at risk by participation in the study.
19. History of diverticulosis requiring antibiotic treatment or any other gastrointestinal 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.

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.