To Evaluate the Blood Levels and Safety of IV and Subcutaneous CDP6038 in Subjects With Rheumatoid Arthritis Using Methotrexate

Study Overview
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Brief Summary
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The primary objectives are to determine the relationship between blood levels of CDP6038 and suppression of C-reactive Protein (CRP) following single doses given as intravenous (IV) infusion or subcutaneous (SC) injection to Rheumatoid Arthritis (RA) patients. The safety of CDP6038 will also be evaluated.

Detailed Description
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The secondary objectives of the study include determination of the absolute bioavailability of CDP6038 given via sc administration compared with iv infusion; assessment of the immunogenicity potential of single dose CDP6038 and assessment, on an exploratory basis, of other relevant systemic biomarkers and changes in clinical response.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single Dose Evaluation of the Pharmacokinetics, Pharmacodynamics and Safety of IV and Subcutaneous CDP6038 in Subjects With Rheumatoid Arthritis on a Stable Dose of Methotrexate

Conditions
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Arthritis, Rheumatoid Arthritis

Intervention / Treatment
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* Biological: CDP6038
* Biological: CDP6038
* Biological: CDP6038
* Other: Placebo IV
* Other: Placebo SC
* Drug: CDP 6038 SC
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RA > 6 months duration on stable Methotrexate ≤9 swollen and ≤9 tender joints (28 joint count) Minimum Screening CRP of 0.5mg/L Exclusion Criteria: Participation in previous studies with defined agents and durations Previous treatment with defined agents and durations Presence of, or history of defined medical conditions including those particularly associated with deficiency in immune response Pregnancy Positive tests/signs of possible latent/active tuberculosis Positive HIV Drug addiction or alcohol abuse

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.1mg/kg and 1mg/kg CDP6038 IV and Placebo IV<br>Cohort 1, Group 1 will compare 0.1mg/kg, 1mg/kg CDP6038 and placebo IV. | Biological: CDP6038<br>* Single dose: 1 mg/kg CDP6038 IV<br>Biological: CDP6038<br>* Single dose: 0.1mg/kg CDP6038 IV<br>Other: Placebo IV<br>* Single dose: Placebo IV<br>Drug: Methotrexate<br>* Individual stable doses of methotrexate.<br>|
| Experimental: 1 mg/kg CDP6038 SC and Placebo SC<br>Cohort 1, Group 2 will compare 1mg/kg CDP6038 and placebo sc. | Biological: CDP6038<br>* Single dose: 1.0mg/kg CDP6038 SC<br>Other: Placebo SC<br>* Single dose: Placebo SC<br>Drug: Methotrexate<br>* Individual stable doses of methotrexate.<br>|
| Experimental: Optimized CDP6038 SC<br>Cohort 2, Group 3 will compare optimized sc doses of CDP6038 based on outcome of Cohort 1 with placebo. | Drug: CDP 6038 SC<br>* Optimized CDP6038 SC doses based on outcome of Cohort 1 with placebo<br>Drug: Methotrexate<br>* Individual stable doses of methotrexate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK/PD relationship between systemic CDP6038 exposure and CRP suppression. |  | For 12 weeks following single dose | 
| Evaluate the safety and tolerability of single doses of CDP6038 For 12 weeks following single dose |  | For 12 weeks following single dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute bioavailability of CDP6038 given by sc injection in comparison with iv infusion |  | For 12 weeks following single dose | 
| Assess the immunogenicity of single dose CDP6038 |  | Multiple sampling from 0 to 12 weeks following single dose | 
| Assess, on an exploratory basis, changes in clinical response and other systemic biomarkers associated with RA |  | For 12 weeks following single dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDP6038