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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Placebo; Drug: dose level 1; Drug: dose level 2; Drug: dose level 3; Drug: dose level 4

• Registration Number: NCT00838565
• Lead Sponsor: Pfizer

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2009-02-04
• Study First Submitted QC: 2009-02-04
• Study First Posted: 2009-02-06
• Study Start: 2009-05-20
• Primary Completion: 2012-02-02
• Study Completion: 2012-02-02
• Results First Submitted: 2017-08-08
• Status Verified: 2018-03
• Results First Submitted QC: 2018-03-12
• Last Update Submitted: 2018-03-12
• Results First Posted: 2018-11-02
• Last Update Posted: 2018-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
PF-04236921	dose level 1	-
PF-04236921	dose level 4	-
PF-04236921	dose level 2	-
PF-04236921	dose level 3	-

Primary Outcome Measures

Name	Time	Method
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 28	Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 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
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Maximum Observed Serum Concentration (Cmax): 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	Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
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	Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624)	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.
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
Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1	Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Serum Decay Half-Life (t1/2): Day 56	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose	Serum decay half-life is the time measured for the serum concentration to decrease by one half.

Trial Locations

Locations (8)

Altoona Center for Clinical Research; 🇺🇸 Duncansville, Pennsylvania, United States

Millennium Research; 🇺🇸 Ormond Beach, Florida, United States

Inha University Hospital, Medicine/Rheumatology; 🇰🇷 Incheon, Korea, Republic of

Seoul National University Hospital, Rheumatology, Internal Medicine; 🇰🇷 Seoul, Korea, Republic of

Hospital Clinico Universitario de Santiago; 🇪🇸 Santiago de Compostela, A Coruña, Spain

Yonsei University College of Medicine, Severance Hospital, Clinical Trial Center; 🇰🇷 Seoul, Korea, Republic of

Complexo Hospitalario Universitario A Coruña; 🇪🇸 A Coruña, Spain

Allergy, Asthma, Arthritis, & Lung; 🇺🇸 Daytona Beach, Florida, United States