Clinical trial NCT01089725: Efficacy And Safety Study Of Tanezumab Subcutaneous Administration In Osteoarthritis - A Subcutaneous/Intravenous Bridging Study
Official title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteoarthritis
Arthritis
Pain
Keywords: safety
efficacy
parallel group
double-blind
multicenter
injection
infusion
osteoarthritis
bridging
subcutaneous
intravenous
tanezumab
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-03-18
Enrollment: 385
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an efficacy and safety study of 3 doses (2.5 mg, 5 mg and 10mg) of tanezumab administered subcutaneously versus placebo. This study will also compare a subcutaneous (SC) administration of 10 mg of tanezumab) with an intravenous (IV) administration of 10 mg of tanezumab. Each person will receive an IV infusion and a SC infusion. The study will last 16 weeks for those who wish to enter a 64-week extension study or 24 weeks for those who do not.

Detailed description: This study was terminated on 08 Nov 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of osteoarthritis (OA) of the knee according to American College of Rheumatology (ACR) criteria with a Kellgren- Lawrence score of greater than or equal to 2
* 18 years of age or greater
* Two methods of birth control one of which must be barrier if of childbearing potential
* Willing to discontinue pain medication except as permitted per protocol

Exclusion Criteria:

* Pregnancy or wishing to be pregnant during the course of the study, lactating women
* Body Mass Index (BMI) greater than 39
* Clinically significant cardiac, neurological, psychiatric conditions and other conditions that are excluded by the protocol.
* Previous exposure to a Nerve Growth Factor (NGF) antibody

Primary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis Score at Week 16
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Weeks 1, 2, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 2, 4, 8, and 12
measure: Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response
timeFrame: Weeks 1, 2, 4, 8, 12, and 16
measure: Percentage of Participants With at Least 30%, 50%, 70% and 90% Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
timeFrame: Weeks 1, 2, 4, 8, 12, and 16
measure: Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score at Weeks 1, 2, 4, 8, 12, and 16
timeFrame: Weeks 1, 2, 4, 8, 12, 16
measure: Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis
timeFrame: Weeks 1, 2, 4, 8, 12, and 16
measure: Change From Baseline in Average Pain Score in the Index Knee at Weeks 1, 2, 4, 8, 12 and 16
timeFrame: Baseline, Weeks 1, 2, 4, 8, 12, and 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 1, 2, 4, 8, 12, and 16
timeFrame: Baseline, Weeks 1, 2, 4, 8, 12, and 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 1, 2, 4, 8, 12, and 16
timeFrame: Baseline, Weeks 1, 2, 4, 8, 12, and 16
measure: Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 1, 2, 4, 8, 12, and 16
timeFrame: Baseline, Weeks 1, 2, 4, 8, 12, and 16
measure: Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 1, 2, 4, 8, 12, and 16
timeFrame: Baseline, Weeks 1, 2, 4, 8, 12, and 16
measure: Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 16
timeFrame: Baseline, Week 16
measure: Time to Discontinuation Due to Lack of Efficacy
timeFrame: Baseline up to Week 24
measure: Percentage of Participants Who Used Rescue Medication
timeFrame: Weeks 1, 2, 4, 8, 12, and 16
measure: Duration of Rescue Medication Use
timeFrame: Weeks 1, 2, 4, 8, 12, and 16
measure: Amount of Rescue Medication Taken
timeFrame: Weeks 1, 2, 4, 8, 12, and 16
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 112 days after last dose of study treatment
measure: Number of Participants With Abnormal Laboratory Findings
timeFrame: Day 1 up to Week 24
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, and 24
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, and 24
measure: Number of Participants With Anti-drug Antibodies (ADA)
timeFrame: Baseline, Weeks 8, 16, 24 or Early Termination
measure: Number of Participants With Abnormal Physical Examination Findings
timeFrame: Baseline up to Week 24
measure: Number of Participants With Clinically Significant Abnormality in Vital Signs
timeFrame: Baseline to Week 24
measure: Number of Participants With Injection and Infusion Site Reactions
timeFrame: Baseline, Weeks 1, 2, 4, 8, 12, 16, and 24
measure: Plasma Tanezumab Concentration
timeFrame: Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, 24 or End of treatment
measure: Total and Free Nerve Growth Factor (NGF) Concentration
timeFrame: Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, and 24 or End of treatment
measure: Number of Participants With Intravenous or Subcutaneous Doses of Study Medication
timeFrame: Baseline up to Week 8
Locations:
city: Montgomery
country: United States
facility: Vaughn H. Mancha, Jr., MD, PC
state: Alabama
city: Mesa
country: United States
facility: Novara Clinical Research
state: Arizona
city: Phoenix
country: United States
facility: Redpoint Research
state: Arizona
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Anaheim
country: United States
facility: West Coast Radiology Center
state: California
city: Burbank
country: United States
facility: Providence Clinical Research
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: La Jolla
country: United States
facility: Allergy and Rheumatology Medical Clinic, Inc.
state: California
city: La Mesa
country: United States
facility: Triwest Research Associates
state: California
city: National City
country: United States
facility: Synergy Clinical Research Center
state: California
city: Sacramento
country: United States
facility: Benchmark Research
state: California
city: Santa Ana
country: United States
facility: Probe Clinical Research Corp.
state: California
city: Santa Ana
country: United States
facility: Trinity Clinical Trials
state: California
city: Upland
country: United States
facility: FMC Clinical Trials
state: California
city: Englewood
country: United States
facility: Colorado Hematology
state: Colorado
city: Englewood
country: United States
facility: Colorado Orthopedic Consultants, P.C.
state: Colorado
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Washington
country: United States
facility: Office of Cynthia Morgan, MD
state: District of Columbia
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Crystal River
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Fleming Island
country: United States
facility: Fleming Island Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Westside Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Largo
country: United States
facility: BayCare Outpatient Imaging at Bardmoor
state: Florida
city: Opa-locka
country: United States
facility: Sunshine Research Center
state: Florida
city: Pinellas Park
country: United States
facility: DMI Research, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: St. Petersburg Arthritis Center
state: Florida
city: Woodstock
country: United States
facility: North Georgia Clinical Research
state: Georgia
city: Woodstock
country: United States
facility: North Georgia Internal Medicine
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Boise
country: United States
facility: Sonoma Clinical Research, LLC.
state: Idaho
city: Boise
country: United States
facility: Sonora Clinical Research
state: Idaho
city: Chicago
country: United States
facility: Apex Medical Research, AMR, Inc.
state: Illinois
city: Wichita
country: United States
facility: Professional Research Network of Kansas, LLC
state: Kansas
city: Wichita
country: United States
facility: Wichita Clinic PA
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Community Research, Inc.
state: Kentucky
city: Metairie
country: United States
facility: BenchMark Research
state: Louisiana
city: Frederick
country: United States
facility: Arthritis Treatment Center
state: Maryland
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Brockton
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Ann Arbor
country: United States
facility: Ann Arbor Clinical Reserch
state: Michigan
city: Troy
country: United States
facility: Troy Internal Medicine, PC
state: Michigan
city: Hattiesburg
country: United States
facility: Arthritis Associates, PLLC
state: Mississippi
city: Billings
country: United States
facility: Billings Clinic Infusion Center
state: Montana
city: Billings
country: United States
facility: Billings Clinic Research Center
state: Montana
city: Lincoln
country: United States
facility: Physician Research Collaboration, LLC
state: Nebraska
city: Omaha
country: United States
facility: Midwest Minor Medical
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research, Inc.
state: Nebraska
city: Omaha
country: United States
facility: Midwest Minor Medical
state: Nebraska
city: Omaha
country: United States
facility: Midwest Minor Medical
state: Nebraska
city: Las Vegas
country: United States
facility: G. Timothy Kelly, MD
state: Nevada
city: Roslyn
country: United States
facility: Andrew Porges, MD, PC
state: New York
city: Charlotte
country: United States
facility: PMG Research of Charlotte
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro Imaging
state: North Carolina
city: Greensboro
country: United States
facility: Pharmquest
state: North Carolina
city: Raleigh
country: United States
facility: Wake Internal Medicine Consultants, Inc.
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
state: Ohio
city: Norman
country: United States
facility: LION Research
state: Oklahoma
city: Norman
country: United States
facility: McBride Clinic
state: Oklahoma
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Lebanon
country: United States
facility: Lebanon Internal Medicine Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Founders Research Corporation
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading, LLP
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Johnson City
country: United States
facility: SoFHA Clinical Research
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc.
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc
state: Texas
city: Houston
country: United States
facility: Westbury Medical Clinic
state: Texas
city: Houston
country: United States
facility: Asif Cochinwala, MD, P.A.
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Houston
country: United States
facility: Houston Institute for Clinical Research
state: Texas
city: Houston
country: United States
facility: Little York Medical Center
state: Texas
city: Kingwood
country: United States
facility: Internist Associates of Texas
state: Texas
city: Nassau Bay
country: United States
facility: Accurate Clinical Research Inc
state: Texas
city: Plano
country: United States
facility: Clinical Investigations of Texas, LLC
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research
state: Texas
city: Sugar Land
country: United States
facility: Pioneer Research Solutions, Inc
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Roanoke
country: United States
facility: Hypothe Test, LLC
state: Virginia
city: Clarksburg
country: United States
facility: Mountain State Clinical Research
state: West Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Berenbaum F, Schnitzer T, Kivitz A, Viktrup L, Johnston E, Yang R, Whalen E, Tive L, Semel D. Gender, age, disease severity, body mass index and diabetes may not affect response to subcutaneous tanezumab in patients with osteoarthritis after 16 weeks of treatment. A subgroup analysis of placebo-controlled trials. Int J Clin Pract. 2021 Dec;75(12):e14975. doi: 10.1111/ijcp.14975. Epub 2021 Oct 21.
citation: Berenbaum F, Schnitzer TJ, Kivitz AJ, Viktrup L, Hickman A, Pixton G, Brown MT, Davignon I, West CR. General Safety and Tolerability of Subcutaneous Tanezumab for Osteoarthritis: A Pooled Analysis of Three Randomized, Placebo-Controlled Trials. Arthritis Care Res (Hoboken). 2022 Jun;74(6):918-928. doi: 10.1002/acr.24637. Epub 2022 Mar 25.
citation: Tive L, Bello AE, Radin D, Schnitzer TJ, Nguyen H, Brown MT, West CR. Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip. J Pain Res. 2019 Mar 19;12:975-995. doi: 10.2147/JPR.S191297. eCollection 2019.