Dose-finding of Multiple Dose of BT061 in Patients With Active Rheumatoid Arthritis Incompletely Controlled on Stable Methotrexate (MTX)

Study Overview
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Brief Summary
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The study is conducted in order to find out if repeated doses of the monoclonal (artificially manufactured) antibody BT061 can help arthritis patients whose disease does not sufficiently respond to a treatment with methotrexate (MTX).

Detailed Description
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Patients showing active rheumatoid arthritis according to ACR criteria despite at least 6 months of treatment with methotrexate fulfilling all other inclusion criteria including written informed consent and none of the exclusion criteria (see below) have the opportunity to be randomised to either treatment with BT061 or placebo, both given subcutaneously in a double-blind set-up.

Official Title
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A Multi-center, Double-blind, Randomized, Placebo-controlled, Dose-finding Study in Patients With Active Rheumatoid Arthritis Incompletely Controlled on Stable MTX Doses to Investigate Efficacy and Safety of SC BT061

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: BT061
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with active Rheumatoid Arthritis (RA) according to 1987 revised ACR criteria with functional class II-III Disease activity at screening and baseline (more than 6 swollen joint count; more than 6 tender joint count; elevat. of CRP or ESR) Duration of RA more than 12 month History of at least one disease-modifying anti-rheumatic drug (DMARD) with an inadequate response despite more than 3 month of treatment MTX treatment at least 6 month with a stable dose at least 15mg MTX Patients could continue at more than daily 7,5mg of prednisone or equivalent stable dose at least 6 weeks prior baseline Written Informed Consent Exclusion Criteria: Treatment with traditional DMARDs apart from MTX 12 weeks prior to baseline and DMARD leflunomide 24 weeks Treatment with any biologics other than TNF-α inhibitors (e.g. abatacept, rituximab, tocilizumab, anakinra) treatment with any TNF-α inhibitor within 5 elimination half-lives prior baseline and during the study Clinical non-response to more than one of TNF-α inhibitor exceeding adequate treatment duration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment<br>BT061 monoclonal antibody (subcutaneous) | Biological: BT061<br>* subcutaneous administration of the monoclonal antibody BT061<br>* Other names: immune-modulatory antibody BT061;|
| Placebo Comparator: Placebo<br>subcutaneous injection of placebo | Biological: Placebo<br>* subcutaneous injection of placebo<br>* Other names: end formulation buffer without active ingredient;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose-response information | ACR20 response (percentage of patients reaching or exceeding at least a 20% improvement in their arthritis assessment according to the criteria of the American College of Rheumatology) | ACR20 response at week 13 (1 week after last dose of study drug) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy responses other than ACR20, including questionaires, and their dose dependencies | ACR50, ACR70, ESR, DAS28, CRP, HAQs, FACIT, RF, Hb, | weekly assessment of ACR arthritis status during the 12 weeks' treatment course, then repeatedly within 1 to12 weeks after the last dose of study drug | 
| Safety and tolerability of the various dose levels and of placebo | Physical examinations Vital Signs, Safety Lab, assessment of adverse events, tolerability | weekly assessment of physical status, safety labs, adverse events during the 12 weeks' treatment course, then repeatedly within 1 to12 weeks after the last dose of study drug | 
| Pharmakokinetics (PK) | BT061 plasma levels, AUC, time to elimination, accumulation after multiple doses, time course of related hematological parameters (e.g. WBC count) | weekly blood sampling during the 12 weeks' treatment course, then repeatedly within 1 to12 weeks after the last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rheumatoid arthritis