Phase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of PF-04236921 administered monthly as three intravenous infusions. Each group of patients will be assigned to a dose level; Safety and tolerability of a low dose level will be required before proceeding to successively higher dose levels. Blood tests will be performed to measure the amount of drug and changes in measures of inflammation.

Detailed Description
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Safety and Tolerability and Pharmacokinetic/Pharmacodynamic assessment of inflammation-related biomarkers.

Official Title
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Phase 1, Randomized, Patient And Investigator-blind, Placebo-controlled Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of Pf-04236921 In Patients With Rheumatoid Arthritis Receiving Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Placebo
* Drug: dose level 1
* Drug: dose level 2
* Drug: dose level 3
* Drug: dose level 4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rheumatoid Arthritis on a stable dose of methotrexate Rheumatoid Arthritis disease activity as assessed by blood tests Exclusion Criteria: Serious or uncontrolled medical conditions Current or recent treatment with disease-modifying drugs other than methotrexate including but not limited to leflunomide, sulfasalazine, etanercept, infliximab, adalimumab, abatacept, rituximab Current oral glucocorticoid dose of more than 10 mg/d prednisone equivalent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* intravenous infusion on three consecutive months<br>|
| Experimental: PF-04236921<br> | Drug: dose level 1<br>* intravenous infusion on three consecutive months<br>Drug: dose level 2<br>* intravenous infusion on three consecutive months<br>Drug: dose level 3<br>* intravenous infusion on three consecutive months<br>Drug: dose level 4<br>* intravenous infusion on 3 consecutive months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to 28 days after last dose or until serum PF-04236921 concentrations were below the LLOQ that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events. | Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624) | 
| Number of Participants With Positive Anti-drug Antibodies Response |  | Day 1, 28, 56, 84, 174, 354, End of Study (Day 624) | 
| Maximum Observed Serum Concentration (Cmax): Day 1 |  | Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose | 
| Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1 |  | Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 1 | AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168). | Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose | 
| Maximum Observed Serum Concentration (Cmax): Day 28 |  | Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose | 
| Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28 |  | Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 28 | AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168). | Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose | 
| Maximum Observed Serum Concentration (Cmax): Day 56 |  | Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose | 
| Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56 |  | Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56 | AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168). | Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose | 
| Serum Decay Half-Life (t1/2): Day 56 | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety and tolerability Pharmacokinetics Pharmacodynamics PF-04236921