Back to resultsPhase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Placebo
dose level 1
dose level 2
dose level 3
dose level 4
Sponsored by
About this trial
This is an interventional other trial for Rheumatoid Arthritis focused on measuring Safety and tolerability Pharmacokinetics Pharmacodynamics PF-04236921
Eligibility Criteria
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
Sites / Locations
- Allergy, Asthma, Arthritis, & Lung
- Millennium Research
- Altoona Center for Clinical Research
- Inha University Hospital, Medicine/Rheumatology
- Seoul National University Hospital, Rheumatology, Internal Medicine
- Yonsei University College of Medicine, Severance Hospital, Clinical Trial Center
- Hospital Clinico Universitario de Santiago
- Complexo Hospitalario Universitario A Coruña
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
PF-04236921
Arm Description
Outcomes
Primary Outcome Measures
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.
Number of Participants With Positive Anti-drug Antibodies Response
Maximum Observed Serum Concentration (Cmax): Day 1
Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1
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).
Maximum Observed Serum Concentration (Cmax): Day 28
Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28
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).
Maximum Observed Serum Concentration (Cmax): Day 56
Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56
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).
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00838565
Brief Title
Phase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
May 20, 2009 (Actual)
Primary Completion Date
February 2, 2012 (Actual)
Study Completion Date
February 2, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Safety and tolerability Pharmacokinetics Pharmacodynamics PF-04236921
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
PF-04236921
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
intravenous infusion on three consecutive months
Intervention Type
Drug
Intervention Name(s)
dose level 1
Intervention Description
intravenous infusion on three consecutive months
Intervention Type
Drug
Intervention Name(s)
dose level 2
Intervention Description
intravenous infusion on three consecutive months
Intervention Type
Drug
Intervention Name(s)
dose level 3
Intervention Description
intravenous infusion on three consecutive months
Intervention Type
Drug
Intervention Name(s)
dose level 4
Intervention Description
intravenous infusion on 3 consecutive months
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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 Frame
Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624)
Title
Number of Participants With Positive Anti-drug Antibodies Response
Time Frame
Day 1, 28, 56, 84, 174, 354, End of Study (Day 624)
Title
Maximum Observed Serum Concentration (Cmax): Day 1
Time Frame
Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Title
Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1
Time Frame
Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 1
Description
AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Time Frame
Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
Title
Maximum Observed Serum Concentration (Cmax): Day 28
Time Frame
Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Title
Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28
Time Frame
Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 28
Description
AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Time Frame
Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
Title
Maximum Observed Serum Concentration (Cmax): Day 56
Time Frame
Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
Title
Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56
Time Frame
Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56
Description
AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Time Frame
Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
Title
Serum Decay Half-Life (t1/2): Day 56
Description
Serum decay half-life is the time measured for the serum concentration to decrease by one half.
Time Frame
Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
Other Pre-specified Outcome Measures:
Title
Change From Baseline in C-Reactive Protein (CRP) Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation
Description
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra sensitive assay. A decrease in the level of CRP indicates reduction in inflammation.
Time Frame
Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation
Title
Change From Baseline in Log CRP Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
Description
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time Frame
Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
Title
Change From Baseline in Absolute Neutrophil Counts at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation
Time Frame
Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation
Title
Change From Baseline in Free Interleukin-6 (IL-6) Concentrations at Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579 and 624
Description
Serum samples were analyzed for IL-6 concentrations using a validated analytical colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) method.
Time Frame
Baseline, Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Allergy, Asthma, Arthritis, & Lung
City
Daytona Beach
State/Province
Florida
ZIP/Postal Code
32114
Country
United States
Facility Name
Millennium Research
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Inha University Hospital, Medicine/Rheumatology
City
Incheon
ZIP/Postal Code
400-711
Country
Korea, Republic of
Facility Name
Seoul National University Hospital, Rheumatology, Internal Medicine
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Yonsei University College of Medicine, Severance Hospital, Clinical Trial Center
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Hospital Clinico Universitario de Santiago
City
Santiago de Compostela
State/Province
A Coruña
ZIP/Postal Code
15706
Country
Spain
Facility Name
Complexo Hospitalario Universitario A Coruña
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
29776017
Citation
Li C, Shoji S, Beebe J. Pharmacokinetics and C-reactive protein modelling of anti-interleukin-6 antibody (PF-04236921) in healthy volunteers and patients with autoimmune disease. Br J Clin Pharmacol. 2018 Sep;84(9):2059-2074. doi: 10.1111/bcp.13641. Epub 2018 Jun 25.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B0151002&StudyName=Phase%20I%20Study%20Of%20The%20Safety%2C%20Tolerability%2C%20Pharmacokinetics%20And%20Pharmacodynamics%20Of%20Multiple%20Intravenously%20Administered%20Doses%20Of%20PF-042369
Description
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Phase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis
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