Study to Assess the Safety and Tolerability of MEDI5117 in Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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Study to assess the safety and tolerability of MEDI5117 in Rheumatoid Arthritis patients

Detailed Description
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A Double-blind, Placebo-controlled, Randomized Study in Rheumatoid Arthritis Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of MEDI5117 (anti-IL-6)

Official Title
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A Double-blind, Placebo-controlled, Randomized Study in Rheumatoid Arthritis Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of MEDI5117 (Anti-IL-6)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: MEDI5117
* Biological: MEDI5117 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active Rheumatoid Arthritis (RA) for 6 months or more. Males or nonpregnant, nonlactating femails aged 20 to 75 years, inclusive. Body Mass Index (BMI) between 19 and 36 kg/m2 and weight between 50 and 145 kg, inclusive. Males, unless surgically sterile, must use 2 effective methods of birth control from Day 1 through follow-up. Exclusion Criteria: History or presence of any clinically significant disease or disorder which has not been stable over the previous 3 months. History of liver disease, bilirubin elevations, or Gilbert's Syndrome. Any systematic inflammatory condition in addition to RA (polymyalgia rheumatica, giant cell arthritis, systemic lupus, gout, pyrophosphate arthropathy). Current, chronic pain disorders including fibromyalgia and chronic regional pain syndromes or chronic fatigue syndromes. Intramuscular steroid injection or intraarticular steroid injection within 1 month of enrollment.

Ages Eligible for Study
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Minimum Age: 20 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: MEDI5117<br>Intravenous infusion administered over 60 minutes | Biological: MEDI5117<br>* Intravenous infusion administered over 60 minutes, will be one of the following doses: 30, 100, 300, or 600 mg<br>|
| Placebo Comparator: MEDI5117 Placebo<br>Intravenous infusion administered over 60 minutes | Biological: MEDI5117 Placebo<br>* Intravenous infusion administered over 60 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the safety profile in terms of adverse events, blood pressure, pulse, temperature, ECG (Electrocardiogram), physical examination, and safety laboratory variables. |  | From Baseline up to 64 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of pharmacokinetics in terms of Maximum serum concentration (Cmax), time to Cmax (tmax), terminal rate constant(λz), terminal half-life (t1/2 λz). |  | From Day 1 Predose, 2h, 12h, 24h, day 7, week 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 56 and week 64. | 
| Description of pharmacokinetics in terms of area under the serum concentration-time curve from zero to the time of the last quantifiable concentration [AUC(0-t)] and from zero to infinity (AUC). |  | From Day 1 Predose, 2h, 12h, 24h, day 7, week 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 56 and week 64. | 
| Description of pharmacokinetics in terms of area under the serum concentration-time curve from zero to the time of concentration at Weeks 6 and 12 [AUC(0-6w) and AUC(0 12w)]. |  | From Day 1 Predose, 2h, 12h, 24h, day 7, week 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 56 and week 64. | 
| Descriptions of pharmacokinetics in terms of systemic clearance (CL), volume of distribution during terminal phase (Vz), and volume of distribution at steady state (Vdss). |  | From Day 1 Predose, 2h, 12h, 24h, day 7, week 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 56 and week 64. | 
| Description of pharmacodynamics in terms of total interleukin 6 (IL-6) and free IL-6 (exploratory) in plasma and high sensitive C-reactive protein (hs-CRP) pre and post MEDI5117 or placebo administration and their corresponding change from baseline. |  | From Baseline day -1 to week 64 | 
| Description of immunogenicity in terms of positive or negative for the presence of antidrug antibodies against MEDI5117 in blood. |  | From Baseline day -1 to week 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Phase I, Biologic