Clinical trial NCT00863772: Tanezumab and Nerve Function In Arthritis Patients
Official title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF TANEZUMAB ON PERIPHERAL NERVE FUNCTION IN PATIENTS WITH OSTEOARTHRITIS.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteoarthritis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-03-18
Enrollment: 220
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: Tanezumab reduces pain of osteoarthritis without affecting how nerve impulses are transmitted in sensory nerves.

Detailed description: This study was terminated on 16 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:

* BMI less or equal to 39 kg/m2
* Osteoarthritis (arthritis) of the knee or hip with pain score that qualifies
* Willing to comply with study visit schedule and study requirements, including, for women of child-bearing potential or male patients with female partners of child-bearing potential, the use of 2 forms of birth control, one of which is a barrier method.
* Patients must consent in writing to participate in the study.

Exclusion Criteria:

* Untreated, uncontrolled diseases,
* Unwilling or unable to discontinue the use of prohibited medications, including other pain medications, during the screening period and during the study,
* Significant cardiac disease within the past 6 months
* Significant neurological disease (e.g. peripheral neuropathy, multiple sclerosis, stroke) or signs of neuropathy at screening
* Known bleeding disorder or anticoagulation therapy
* Planned surgery during the study period
* History of alcoholism or drug abuse in the past 2 years
* Unable to use acetaminophen
* Use of a biologic (including live vaccines, with the exception of Flumist) within the past 3 months
* Allergic reaction to a biologic or an antibody in the past
* Disqualifying laboratory values, including Hepatitis B or C, HIV or drug test
* Cancer in the past 5 years. Basal cell or squamous cell carcinoma are okay.
* Medical condition that may interfere with study endpoints or safety of the subject as determined by the investigator.

Primary outcomes:
measure: Change From Baseline in 5 Nerve Conduction Tests-Normal Deviate and Heart Rate Deep Breathing-Normal Deviate (5NC [nd] + HRdb [nd]) Composite Score at Week 24: Intent to Treat (ITT) Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in 5 Nerve Conduction Tests-Normal Deviate and Heart Rate Deep Breathing-Normal Deviate (5NC [nd] + HRdb [nd]) Composite Score at Week 24: Per Protocol Analysis Set (PPAS)
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in Neuropathy Impairment Score - Lower Limbs [NIS (LL)] at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Neuropathy Impairment Score (NIS) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Neuropathy Symptoms and Change (NSC) Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: ITT Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: PPAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: ITT Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: PPAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: ITT Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: PPAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: ITT Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: PPAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in 5 Nerve Conduction Test - Normal Deviate [5NC (nd)] at Week 24: ITT Analysis Set
timeFrame: Baseline, Week 24
measure: Change From Baseline in 5 Nerve Conduction Test - Normal Deviate (5NC [nd]) at Week 24: PPAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Protein Gene Product (PGP) 9.5-Positive Intraepidermal Epidermal Nerve Fiber (IENF) Density at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Change From Baseline in the Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response
timeFrame: Weeks 8, 16, and 24
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 8, 16, and 24
measure: Percentage of Participants With Improvement of At Least 2 Points From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis
timeFrame: Weeks 8, 16, and 24
measure: Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
timeFrame: Week 16
measure: Change From Baseline in Average Pain Score in the Index Knee/Hip Joint at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 16, 17, 18, 19, 20, 21, 22, 23, and 24
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 16, 17, 18, 19, 20, 21, 22, 23, and 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Change From Baseline in WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Change From Baseline in WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 8, 16, and 24
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants With Rescue Medication Usage
timeFrame: Week 8, 16, 24
measure: Number of Days With Rescue Medication Usage
timeFrame: Weeks 8, 16, and 24
measure: Amount of Rescue Medication Used
timeFrame: Weeks 8, 16, and 24
measure: Number of Participants With Anti-Drug Antibody (ADA)
timeFrame: pre-dose on Day 1 (Baseline), Week 8, 16, 24, 32
measure: Plasma Trough Concentration of Tanezumab
timeFrame: pre-dose on Day 1 (Baseline), Weeks 8, 16, 24, and 32
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline through 112 days after last Intravenous dose of Investigational product to last participant treated with study medication on study (up to Week 32 after last IV dose of investigational product to last participant treated)
Other outcomes:
measure: Number of Participants With Intravenous Doses of Study Medication
timeFrame: Day 1 up to Week 24
Locations:
city: Jonesboro
country: United States
facility: NEA Baptist Clinic
state: Arkansas
city: Aurora
country: United States
facility: JDP Medical Research, LLC
state: Colorado
city: Centennial
country: United States
facility: Alpine Neurology
state: Colorado
city: Centennial
country: United States
facility: Peak Anesthesia
state: Colorado
city: Atlantis
country: United States
facility: JEM Research, LLC
state: Florida
city: Atlantis
country: United States
facility: Medical Specialists of the Palm Beaches
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc
state: Florida
city: Bradenton
country: United States
facility: Manatee Internal Medicine
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Fort Myers
country: United States
facility: Harris Bonnette, MD
state: Florida
city: Hollywood
country: United States
facility: Sunrise Clinical Research, Inc.
state: Florida
city: Hollywood
country: United States
facility: Sunrise Clinical Research, Inc
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic, Inc
state: Florida
city: Miami
country: United States
facility: International Research Associates, LLC
state: Florida
city: Palm Harbor
country: United States
facility: The Arthritis Center
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Neurological Associates
state: Florida
city: Pembroke Pines
country: United States
facility: Pembroke Clinical Trials
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Neurological Associates
state: Florida
city: Pinellas Park
country: United States
facility: Advent Clinical Research Centers, Inc
state: Florida
city: Pinellas Park
country: United States
facility: Advent Clinical Research Center
state: Florida
city: Plantation
country: United States
facility: Berma Research Group
state: Florida
city: Saint Petersburg
country: United States
facility: Carol L. Pappas MD, PhD
state: Florida
city: Saint Petersburg
country: United States
facility: Carol L. Pappas, M.D. PhD
state: Florida
city: Saint Petersburg
country: United States
facility: Dale G. Bramlet, MD, P.L.
state: Florida
city: Sarasota
country: United States
facility: Kennedy-White Orthopaedic Center
state: Florida
city: Sarasota
country: United States
facility: Ronal Aung-Din, MD
state: Florida
city: Sarasota
country: United States
facility: Ronald Aung-Din, MD
state: Florida
city: Sarasota
country: United States
facility: Sarasota Center for Clinical Research
state: Florida
city: South Miami
country: United States
facility: Arthritis & Rheumatic Care Center
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: South Miami
country: United States
facility: Neuroscience Consultants, LLC
state: Florida
city: Tampa
country: United States
facility: Tampa Neurology Associates
state: Florida
city: Tampa
country: United States
facility: Tampa Medical Group, P.A.
state: Florida
city: Venice
country: United States
facility: Radiology Associates of Venice & Englewood
state: Florida
city: Venice
country: United States
facility: Lovelace Scientific Resources, Inc
state: Florida
city: Venice
country: United States
facility: Venice Arthritis Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Neurology
state: Georgia
city: Atlanta
country: United States
facility: Diagnostic Imaging of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: NeuroTrials Research, Incorporated
state: Georgia
city: Austell
country: United States
facility: Northwest Neurology, P.C.
state: Georgia
city: Decatur
country: United States
facility: Atlanta Knee and Sports Medicine
state: Georgia
city: Decatur
country: United States
facility: Joseph D. Weissman, MD
state: Georgia
city: Decatur
country: United States
facility: Neurology Specialists of Decatur
state: Georgia
city: Decatur
country: United States
facility: Southeastern Center for Clinical Trials
state: Georgia
city: Decatur
country: United States
facility: Jefrey D. Lieberman, MD
state: Georgia
city: Bannockburn
country: United States
facility: Northwestern Lake Forest Hospital Diagnostic Imaging Centers
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Northbrook
country: United States
facility: Consultants in Neurology, Ltd.
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Indianapolis
country: United States
facility: University Hospital
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Las Vegas
country: United States
facility: G. Timothy Kelly, MD
state: Nevada
city: Las Vegas
country: United States
facility: Clinical Neurology Specialists
state: Nevada
city: Lake Success
country: United States
facility: Neurological Associates of Long Island, P.C.
state: New York
city: Roslyn
country: United States
facility: Andrew J. Porges, M.D. PC
state: New York
city: Asheville
country: United States
facility: Asheville Imaging
state: North Carolina
city: Asheville
country: United States
facility: Biltmore Medical Associates
state: North Carolina
city: Asheville
country: United States
facility: Clinical Study Center of Asheville, LLC
state: North Carolina
city: Asheville
country: United States
facility: Asheville Neurology
state: North Carolina
city: Hickory
country: United States
facility: Unifour Medical Research Associates, LLC
state: North Carolina
city: Hickory
country: United States
facility: Neurology Associates, PA
state: North Carolina
city: Hickory
country: United States
facility: Unifour Medical Research Associates, LLC
state: North Carolina
city: Lenoir
country: United States
facility: Caldwell Memorial Hospital
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research
state: North Carolina
city: Toledo
country: United States
facility: Ohio Research Center
state: Ohio
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Bend
country: United States
facility: North Star Neurology
state: Oregon
city: Altoona
country: United States
facility: Altoona Hospital Campus
state: Pennsylvania
city: Altoona
country: United States
facility: Blair Neurologic Associates
state: Pennsylvania
city: Altoona
country: United States
facility: Blair Medical Associates
state: Pennsylvania
city: Altoona
country: United States
facility: Blair Orthopedic Associates, Inc.
state: Pennsylvania
city: Altoona
country: United States
facility: Bon Secour Campus
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Goose Creek
country: United States
facility: Coastal Carolina Research Center in Goose Creek
state: South Carolina
city: Goose Creek
country: United States
facility: Tidewater Neurology
state: South Carolina
city: Amarillo
country: United States
facility: AAMR Research Clinic, PA
state: Texas
city: Amarillo
country: United States
facility: Amarillo Diagnostic Clinic
state: Texas
city: Dallas
country: United States
facility: Radiant Research, Inc.
state: Texas
city: Dallas
country: United States
facility: Dr. Michael Vengrow
state: Texas
city: Houston
country: United States
facility: Foundation for Southwest Orthopedic Research
state: Texas
city: Houston
country: United States
facility: The Neurology Center
state: Texas
city: San Antonio
country: United States
facility: Paragon Research Center, LLC
state: Texas
city: San Antonio
country: United States
facility: Baptist M&S Imaging
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: San Antonio
country: United States
facility: Christine L. Truitt, MD
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: San Antonio
country: United States
facility: Neurodiagnostic Laboratories of San Antonio, Inc.
state: Texas
city: San Antonio
country: United States
facility: Neurodiagnostic Laboratories of San Antonio, Inc
state: Texas
city: San Antonio
country: United States
facility: Radiant Research Inc.
state: Texas
city: Arlington
country: United States
facility: IntegraTrials, L.L.C
state: Virginia
city: Arlington
country: United States
facility: TLC Neurology, P.L.L.C
state: Virginia
city: Arlington
country: United States
facility: Virginia Hospital Center
state: Virginia
city: Roanoke
country: United States
facility: Hypothe Test, LLC
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Everett
country: United States
facility: Evergreen Neurology and Neurodiagnostics, PLLC
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.
citation: Brown MT, Herrmann DN, Goldstein M, Burr AM, Smith MD, West CR, Verburg KM, Dyck PJ. Nerve safety of tanezumab, a nerve growth factor inhibitor for pain treatment. J Neurol Sci. 2014 Oct 15;345(1-2):139-47. doi: 10.1016/j.jns.2014.07.028. Epub 2014 Jul 18.