E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with active rheumatoid arthritis incompletely controlled on stable MTX doses. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Is to investigate dose-response information on efficacy.
Primary efficacy variable is ACR20 (at Week 13).
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E.2.2 | Secondary objectives of the trial |
Is to investigate dose-response on efficacy, tolerability, safety, and pharmacokinetics (PK). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To participate in this trial, patients must meet all the following criteria:
1. Written informed consent 2. Patients of both gender with active RA according to 1987 revised American College of Rheumatology (ACR) criteria with functional class II-III 3. Disease activity at screening and baseline: a. ≥ 6 swollen joints on 66 joint count and b. ≥ 6 tender joints on 68 joint count and c. ≥ 1 out of the 2 criteria: i. erythrocyte sedimentation rate (ESR) male, ≤ 50 years: ≥ 23 mm/H male, > 50 years: ≥ 30 mm/H female, ≤ 50 years: ≥ 30 mm/H female: > 50 years: ≥ 45 mm/H ii. C-reactive protein (CRP) ≥ 8 mg/L 4. Duration of RA ≥ 12 months 5. Aged 18 years - 75 years (extremes included) 6. Body mass index (BMI) 18 kg/m2 - 30 kg/m2 (extremes included) 7. History of at least one traditional disease modifying anti-rheumatic drug (DMARD) with an inadequate response despite ≥ 3 months of treatment 8. Oral or parenteral MTX treatment for ≥ 6 months with an unchanged mode of application and stable MTX dose ≥ 15 mg (or ≥ 10 mg in case of MTX intolerance) and ≤ the upper limit of the applicable Summary of Product Charac-teristics (SmPC) for at least 8 weeks prior to baseline 9. Patients could continue to receive ≤ 7.5 mg daily of oral corticosteroids (prednisone or equivalent) at the same dose received prior to the study if dose was stable for ≥ 6 weeks prior to baseline, if applicable 10. Patients could continue to receive non-steroidal antiinflam-matory drugs (NSAIDs) at the same dose as received prior to the study if dose was stable for ≥ 2 weeks prior to baseline, if applicable 11. No acute or clinically relevant abnormalities in electrocar-diogram (ECG; 12-lead) at screening and baseline 12. The following blood test results must be fulfilled at screen-ing: a. Hemoglobin ≥ 8.5 g/dL b. Hematocrit > 30% c. White blood cells (WBC) > 3.5*10E9 cells/L d. Neutrophils ≥ 1.5*10E9 cells/L e. CD4 > 0.4*10E9 cells/L f. B-cell count (CD19 count) > 75% of the lower limit of normal range (LLN) g. Platelets ≥ 150*10E9 cells/L
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E.4 | Principal exclusion criteria |
1. Treatment with traditional DMARDs apart from MTX 12 weeks prior to baseline and for DMARD leflunomide 24 weeks (except specific leflunomide wash out proce-dure, i. e. 11 days with colestyramine or activated charcoal plus 30 days wash-out ) prior to baseline 2. Treatment with any biologics other than TNF-α inhibitors (e.g. abatacept, rituximab, tocilizumab, anakinra) 3. Treatment with any TNF-α inhibitor within 5 elimination half-lives prior to baseline (e.g. certolizumab 10 weeks, adalimumab 10 weeks, etanercept 3 weeks, infliximab 7 weeks, golimumab 10 weeks) and during the study 4. Clinical non-response to more than one previous TNF-α inhibitor treatment exceeding adequate treatment duration 5. Serious adverse drug reaction to previous biological treat-ment 6. Intra-articular, intramuscular, or intravenous corticosteroid treatment within 4 weeks prior to screening and during the study 7. Previous therapy with CD4 monoclonal antibody (mab) BT061 8. Serum transaminases, alanine transaminase (ALAT) and/or aspartate transaminase (ASAT) > 2.5 fold ULN at screening 9. Bilirubin > 3 mg/dL at screening 10. Alkaline phosphatase > 2 fold ULN at screening 11. Urea nitrogen > 1.5 fold ULN at screening 12. Kidney insufficiency as defined by creatinine level > 1.5 mg/dl at screening 13. History of severe allergic or anaphylactic reaction to pro-teins of human origin (e.g. vaccination reaction, biological therapy) 14. Presence or history of malignancy within the previous 5 years (except completely resected squamous or basal cell carcinoma of the skin) 15. Presence or history of clinically significant major disease (e.g. severe heart/lung disease New York Heart Associa-tion [NYHA] Class ≥ 3, autoimmune disease [apart from rheumatoid arthritis], acute uncontrolled hyper- or hypo-thyreoidism, severe uncontrolled hypo- or hypertension) 16. Serious local (e.g. abscess) or systemic (e.g. pneumonia, septicemia) infection or recurrent chronic infections within 6 weeks prior to screening visit or during the screening period 17. Any infection requiring antibiotic therapy by any route of administration within 2 weeks prior to baseline 18. Vaccination with live, live attenuated, and/or killed vac-cines in the 12 weeks prior to the first administration of the study drug and during the study 19. Positive diagnosis for acute or chronic infections (i.e. He-patitis C Virus [HCV], Hepatitis B Virus [HBV], Human Im-munodeficiency Virus [HIV]) at Screening visit or history of previous chronic infection 20. Acute or clinically symptomatic Epstein-Barr Virus (EBV) (infectious mononucleosis) or Cytomegalovirus (CMV) in-fection 21. Presence or history of latent or active tuberculosis 22. Presence or history of recurrent acute inflammatory joint disease other than RA 23. Known immune deficiency 24. Presence or history of lymphoproliferative disease, includ-ing lymphoma and lymphadenopathy 25. Presence or history of clinically significant drug or alcohol abuse 26. Joint surgery within 2 months prior to screening 27. The patient, planned to be enrolled, is an employee of any involved study investigator or any involved institution in-cluding the study sponsor 28. Pregnant or nursing women or women of childbearing potential (unless surgically sterile) who are not using two independent effective contraceptive methods during the study and for at least 3 months after the last administration of study drug (e.g. oral or injectable contraceptives, intrauterine devices, double-barrier method, contraceptive patch, or female sterilization) and male subjects who are not using two independent effective contraceptive methods or who are planning a sperm donation at any time during the entire study participation or in the 3 months after the last study drug administration 29. Patients planning to donate blood between 56 days before baseline (Visit T1) and study end (Visit F6) 30. Participation in another clinical trial within 90 days before entering or during the study 31. Inability or lacking motivation to adhere to the study re-quirements and to comply with the study schedule
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E.5 End points |
E.5.1 | Primary end point(s) |
The ACR20 criteria will be used as the primary endpoint to investigate the (relative) difference in disease activity at baseline and at study Week 13 after 12 weeks of treatment.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |