Clinical trial NCT00838565: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Safety and tolerability Pharmacokinetics Pharmacodynamics PF-04236921
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-02-06
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624)
measure: Number of Participants With Positive Anti-drug Antibodies Response
timeFrame: Day 1, 28, 56, 84, 174, 354, End of Study (Day 624)
measure: Maximum Observed Serum Concentration (Cmax): Day 1
timeFrame: Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
measure: Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1
timeFrame: Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 1
timeFrame: Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
measure: Maximum Observed Serum Concentration (Cmax): Day 28
timeFrame: Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
measure: Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28
timeFrame: Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 28
timeFrame: Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
measure: Maximum Observed Serum Concentration (Cmax): Day 56
timeFrame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
measure: Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56
timeFrame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56
timeFrame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
measure: Serum Decay Half-Life (t1/2): Day 56
timeFrame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
Secondary outcomes:
Other outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
measure: 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
timeFrame: 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
measure: 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
timeFrame: Baseline, Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
Locations:
city: Daytona Beach
country: United States
facility: Allergy, Asthma, Arthritis, & Lung
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital, Medicine/Rheumatology
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, Rheumatology, Internal Medicine
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine, Severance Hospital, Clinical Trial Center
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
state: A Coruña
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.