A 24-week, placebo-controlled, multicenter study to investigate the efficacy and safety of tregalizumab (BT061) in combination with methotrexate in the treatment of subjects with active rheumatoid arthritis who have had an insufficient response to methotrexate alone, followed by a 24-week extension phase:T cell REgulating Arthritis Trial 2b (TREAT 2b)

Conditions: Subjects with active rheumatoid arthritis incompletely controlled on stable MTX doses
MedDRA version: 14.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2013-000114-38-HU

Lead Sponsor: Biotest AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 304

Inclusion Criteria

1. Subject demonstrates active RA according to the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA with functional class I–III for =6 months.
2. Subject receives oral or parenteral MTX treatment for =12 weeks (overall), with
an unchanged mode of application and stable MTX dose of =15 mg per week (or =12.5 mg per week in case of MTX intolerance), but no more than the highest locally approved dose for RA, for =8 weeks prior to baseline. The dose of MTX is expected to remain stable throughout the study and may be adjusted only for
safety reasons. If applicable, the dose of folic acid must be unchanged for =8 weeks prior to baseline.
3. Subject meets the following two criteria at both screening and baseline:
- At least 6 swollen joints at 28-joint assessment.
- At least 6 tender joints at 28-joint assessment.
4. Subject has an erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) above the upper limit of normal (ULN) at screening. These tests may be repeated once during the screening period at the discretion of the investigator.
5. Subject is =18 and =75 years of age.
6. Subject has a body mass index =18 and =35 kg/m².
7. Subject receives treatment with corticosteroids =10 mg prednisone equivalent,
stable for at least 4 weeks prior to baseline and during the study, if applicable.
8. Subject receives treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable for at least 2 weeks prior to baseline and during the study, if applicable.
9. Female subjects of childbearing potential: has both a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
10. Subject is judged to be in good general health as determined by the investigator
based upon the results of medical history, laboratory profile, physical examination, chest X-ray (within 3 months before screening date is acceptable), and 12-lead electrocardiogram (ECG).
11. Subject has a cluster of differentiation 4 (CD4) cell count of >400/µL at screening.
12. Subject is willing and able to provide written informed consent.
13. Subject is willing and able to self administer SC injections or has a qualified person available to administer SC injections.
From week 24 onwards:
14. Subject has completed the main phase of the study (Visit V10 at 24 weeks)
15. Subjects who experienced a SAE or a medically significant laboratory or ECG abnormality in the main phase of the study who have not been previously discontinued must have completely recovered prior to entering the extension phase.
16. Subject must have a CD4 cell count of 400/µL at Week 16.
17. Subjects must have achieved a reduction in TJC and SJC of =20% at Week 24
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 243
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 61

Exclusion Criteria

1. Subject has previous exposure to any systemic biologic therapy (details in protocol), to Janus kinase (JAK) or spleen tyrosine kinase (SYK) inhibitors, or to tregalizumab. Previous treatment with an anti-TNF agent is allowed only, if all of the following criteria apply:
- treatment was stopped for reasons other than lack of efficacy or adverse events (AEs)
- treatment was stopped at least 12 weeks or five half-lives of the compound prior to baseline (whichever is longer), and - the treatment period did not exceed 6 weeks.
2. Subject received treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) apart from MTX in the 12 weeks prior to baseline, and for DMARD leflunomide in the 24 weeks prior to baseline (exeptions in protocol).
3. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the 4 weeks prior to baseline. Inhaled corticosteroids for stable medical conditions are allowed.
4. Subject has undergone joint surgery in the 12 weeks prior to baseline (at joints to be assessed within the study) or has undergone major surgery in the 8 weeks prior to baseline.
5. Subject has a history of acute inflammatory joint disease of an origin other than RA or subject has any other rheumatic disease other than RA . However, subjects may have secondary Sjögren's syndrome.
6. Vaccination with live vaccines in the 12 weeks prior to baseline or vaccination with killed vaccines in the 4 weeks prior to baseline.
7. Subject has a history of an allergic reaction or significant sensitivity to constituents of study drugs or a history of severe allergic or anaphylactic reaction to proteins of human origin.
8. Subject has participated in another clinical study in the 90 days prior to baseline or within 5 half lives of the investigated compound—whichever is longer—or plans to do so during the study.
9. Subject has a poorly controlled medical condition - detailed list in the protocol.
10. Subject has a history of clinically significant hematologic, renal, or liver disease , or gastroenteric ulcer or has, at screening, clinically relevant deviations in laboratory tests - detailed list in the protocol.
11. Subject has a presence or history of malignancy within the previous 5 years (exeptions in protocol).
12. Subject has a presence or history of lymphoproliferative disease.
13. Subject has a positive diagnosis for acute or chronic infections (list in protocol).
14. Subject has a history or presence of active or latent tuberculosis.
15. Subject has an acute or clinically symptomatic Epstein Barr virus (EBV) or cytomegalovirus (CMV) infection.
16. Subject has a serious local or systemic infection or recurrent chronic infections in the 6 weeks prior to the screening visit (Visit V1) or during the screening period.
17. Subject has any infection requiring antibiotic or antiviral therapy by any route of administration in the 2 weeks prior to baseline.
18. Subject currently uses or plans to use anti retroviral therapy at any time during the study.
19. Subject received an alkylating agent in the 6 months prior to baseline.
20. Subject has a history of clinically significant drug or alcohol abuse within the last 12 months.
21.Subject is a pregnant or nursing woman or is considering becoming pregnant during the study or in the 3 months after the last dose of study drug.
22.Subject is a woman of childbearing potential (unless surgically sterile or post menopausal >52 weeks) who i

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy and safety of three doses of tregalizumab administered<br>over 24 weeks, followed by a 24-week extension phase (active treatment only), in<br>combination with methotrexate (MTX), for the treatment of adult subjects with active<br>rheumatoid arthritis (RA) who have had an inadequate response to MTX alone<br>(MTX-IR).;Secondary Objective: Not applicable;Primary end point(s): The proportion of subjects who achieve an ACR20 at Week 12 following treatment with tregalizumab (25 mg, 100 mg or 200 mg) + MTX compared with subjects treated with placebo + MTX.;Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome Measures

Name	Time	Method

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