A randomized, placebo-controlled, double-blind, dose escalation study to evaluate the efficacy, safety and tolerability of the study drug BT971 in patients with rheumatoid arthritis receiving concomitant Methotrexate - n.a.

Conditions: Active rheumatoid arthritis, functional class II-III
MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

Registration Number: EUCTR2008-001241-26-HU

Lead Sponsor: Biotest AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 110

Inclusion Criteria

1. Female and male patients with active rheumatoid arthritis.
2. ACR criteria for diagnosis of RA, functional class II-III.
3. Active RA as defined by:
more or equal to 6 swollen joints on 66 joint count.
more or equal to 6 tender joints on 68 joint count.
more or equal to 2 of the following: Erythrocyte Sedimentation Rate (ESR) ³ 28 mm/h, morning stiffness ³ 45 min., C-reactive Protein (CRP) ³ 20 mg/L.
4. Age limitations of ³ 18 years and £ 75 years.
5. Body mass index (BMI) between 18 and 30 kg/m2 inclusive, with a body weight between 50 - 110 kg.
6. At least one traditional DMARD inadequate response despite ³ 3 months of treatment.
7. Concurrent RA medications with stable doses of MTX for ³ 3 months before enrollment (15 to 20 mg per week or as low as 10 mg per week for patients unable to tolerate higher doses)
8. Concomitant medication with oral corticosteroids is allowed if stable dose of max. 10 mg (equivalent to prednisone) per day for ³ 4 weeks prior to Screening.
9. Concomitant medication with NSAIDs is allowed if stable dose for ³ 4 weeks prior to Screening.
10. No acute or relevant abnormalities in ECG.
11. Laboratory results:
·Hemoglobin: ³ 8.5 g/Dl.
·Hematocrit: > 30%.
·White Blood Cells (WBC): ³ 3.5 x 109 cells/L.
·CD4 count: > 0.4 x 109 cells/L.
·Neutrophils: ³ 1.5 x 109 cells/L.
·Platelets: ³ 150 x 109 cells/L.
·Serum transaminases (ALAT, ASAT): £ 3 times the upper limit of normal.
·Bilirubin: < 3 mg/Dl.
·Alkaline phosphatase: £ 2 times the upper limit of normal.
·Urea nitrogen: < 1.5 times the upper limit of normal.
12. B-cell count: ³ 75% of the lower limit of normal.
13. Signed and dated written informed consent.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pre- and concomitant treatment with DMARDs other than Methotrexate, biological product(s), and intraarticular, intramuscular, or intravenous corticosteroids during the last 4 weeks prior to study inclusion and during the entire study.
2. Previous therapy with CD4 mab (note, that a patient who took participation in Step 1 should not be enrolled in Step 2, since this patient has already been treated with BT971).
3. Therapy with Adalimumab or Infliximab in the last 8 weeks and therapy with Etanercept in the last 4 weeks prior to study inclusion and during the entire study.
4. Therapy with Rituximab in the last 6 months prior to study inclusion and during the entire study.
5. Known therapy with Abatacept.
6. Kidney insufficiency as defined by creatinine clearance: < 60 ml/min (Cockcroft Gault equation).
7. History of severe allergic or anaphylactic reaction to proteins of human origin (e.g., vaccination reaction).
8. Known malignancy or history of malignancy within the previous 5 years with no evidence of recurrence.
9. History of clinically significant major disease, i.e., severe heart/lung disease NYHA more or equal to 3 (New York Heart Association: class III: patients with marked limitation of activity; comfortable only at rest), autoimmune disease.
10. Serious local (e.g., abscess) or systematic infection (e.g., pneumonia, septicaemia) within previous 3 months.
11. Vaccinated with live, live attenuated, and/or killed vaccines in the previous 3 months prior to the first administration of the study drug.
12. Positive diagnosis for acute or chronic infections (i.e., HBV, HCV, HIV).
13. History of positive diagnosis for active tuberculosis.
14. History of or recurrent acute inflammatory joint disease other than RA.
15. Known immune deficiency.
16. History of lymphoproliferative disease, including lymphoma and lymphadenopathy.
17. History of clinically significant drug or alcohol abuse.
18. The patient, planned to be enrolled is an employee of any involved study investigator or any involved institution including the study sponsor.
19. Joint surgery within 2 months prior to Screening.
20. Pregnant or nursing women, or woman of childbearing potential who are not using an effective contraceptive method during the study and at least four months after the last administration of study drug (e.g., oral or injectable contraceptives, intrauterine devices, double-barrier method, contraceptive patch, female sterilization, or condoms). Male patients should also maintain reliable contraceptive methods during the entire study participation and at least four months after the last study drug administration.
21. Participation in another clinical trial within 90 days before entering the study or during the study.
22. Inability or lacking motivation to participate in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy, safety and tolerability of BT061 mab therapy in patients receiving concomitant Methotrexate (MTX).;Secondary Objective: ;Primary end point(s): Primary efficacy endpoint:<br><br>The primary endpoint of this study is the ACR 20 response after 8 weeks of treatment with:<br>1. 0.5 mg BT061 + Methotrexat,<br> 2.0 mg BT061 + Methotrexat <br> or Placebo + Methotrexat<br>for Step 1<br>and<br>2. 10 mg BT061 + Methotrexat or<br> Placebo + Methotrexat <br>for Step 2

Secondary Outcome Measures

Name	Time	Method

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