Back to resultsLong-Term Study Of The Safety Of Tanezumab In Arthritis Patients
Primary Purpose
Osteoarthritis
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Tanezumab
Tanezumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- Patients must consent in writing to participate in the study.
- Patients must be 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 have participated in the A4091026 study.
Exclusion Criteria:
- Withdrawn from the A4091026 study for an adverse event or serious adverse event.
- Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to be pregnant during the course of clinical study.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Sites / Locations
- Jem Research, LLC
- Medical Specialists of the Palm Beaches
- Clinical Physiology Associates, Clinical Study Center
- Harris Bonnette, MD
- Arthritis & Rheumatic Care Center
- Miami Research Associates
- Neuroscience Consultants, LLC
- Asheville Imaging
- Biltmore Medical Associates
- Clinical Study Center of Asheville, LLC
- Asheville Neurology
- Ohio Research Center
- Blair Neurologic Associates
- Altoona Center for Clinical Research
- Coastal Carolina Research Center in Goose Creek
- Tidewater Neurology
- Neurodiagnostic Laboratories of San Antonio, Inc
- Radiant Research, Inc.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Tanezumab 5 mg
Tanezumab 10 mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change From A4091026 (NCT00863772) Baseline in 5 Nerve Conduction Tests, Normal Deviate and Heart Rate-Deep Breathing, Normal Deviate (5NC [nd] + HRdb-[nd]) Composite Score at Week 24
5NC(nd)+HRdb(nd)composite score included 5 Nerve Conduction Studies(NCS)attributes(peroneal motor nerve distal latency [MNDL],peroneal nerve compound muscle action potential[CMAP],peroneal motor nerve conduction velocity[MNCV],tibial MNDL,sural sensory nerve action potential amplitude [SNAP])and HRdb value. Values of attributes scored as percentile(calculated from distribution of normal values corresponding to participant's baseline demographic characteristics),then expressed as normal deviate(nd)score based on standard normal distribution.Score >0=worse response,less than(<)0=better response compared to normal matched population.Score change>0=worsening,<0=improvement compared to baseline.2 neurological visits(NVs) were conducted both at baseline and Week 24. NCS measurements were collected once at each NV.HRdb measurements were collected twice and highest nd score was selected at each NV. Mean of selected measurements at each NV was calculated to obtain Baseline and Week 24 values.
Secondary Outcome Measures
Change From A4091026 (NCT00863772) Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) at Week 24
NIS-LL:assess muscle weakness, reflexes, sensation;scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion,hip and knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors) scored on scale 0(normal) to 4(paralysis),higher score=greater weakness. Components of reflexes(quadriceps femoris,triceps surae);sensation (touch pressure,pin-prick,vibration,joint position) scored 0=normal,1=decreased, or 2=absent. NIS-LL score: sum of scores of NIS items 17-24, 28-29 and 34-37. Total possible NIS-LL score range 0-88,high score=more impairment.
Change From A4091026 (NCT00863772) Baseline in Neuropathy Impairment Score (NIS) at Week 24
NIS: 74 items, assess muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0-244, higher score=greater impairment.
Change From A4091026 (NCT00863772) Baseline in Neuropathy Symptoms and Change (NSC) Score at Week 24
NSC score is the number of the 38 symptom questions where the participants indicated experiencing the symptom to any severity. Total score range: 0 to 38 where higher score indicated more symptoms.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00960804
Brief Title
Long-Term Study Of The Safety Of Tanezumab In Arthritis Patients
Official Title
A PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER, LONG-TERM SAFETY STUDY OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
February 15, 2010 (Actual)
Primary Completion Date
November 11, 2010 (Actual)
Study Completion Date
November 11, 2010 (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
Tanezumab, administered for up to 1 1/2 years, reduces the pain of osteoarthritis without affecting how nerve impulses are transmitted in sensory nerves
Detailed Description
This study was terminated on 11 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tanezumab 5 mg
Arm Type
Experimental
Arm Title
Tanezumab 10 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
Tanezumab
Intervention Description
IV, 5 mg dose, q 8 weeks, for up to 80 weeks
Intervention Type
Biological
Intervention Name(s)
Tanezumab
Intervention Description
IV, 10 mg dose, q 8 weeks, for up to 80 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
IV, q 8 weeks, for up to 80 weeks
Primary Outcome Measure Information:
Title
Change From A4091026 (NCT00863772) Baseline in 5 Nerve Conduction Tests, Normal Deviate and Heart Rate-Deep Breathing, Normal Deviate (5NC [nd] + HRdb-[nd]) Composite Score at Week 24
Description
5NC(nd)+HRdb(nd)composite score included 5 Nerve Conduction Studies(NCS)attributes(peroneal motor nerve distal latency [MNDL],peroneal nerve compound muscle action potential[CMAP],peroneal motor nerve conduction velocity[MNCV],tibial MNDL,sural sensory nerve action potential amplitude [SNAP])and HRdb value. Values of attributes scored as percentile(calculated from distribution of normal values corresponding to participant's baseline demographic characteristics),then expressed as normal deviate(nd)score based on standard normal distribution.Score >0=worse response,less than(<)0=better response compared to normal matched population.Score change>0=worsening,<0=improvement compared to baseline.2 neurological visits(NVs) were conducted both at baseline and Week 24. NCS measurements were collected once at each NV.HRdb measurements were collected twice and highest nd score was selected at each NV. Mean of selected measurements at each NV was calculated to obtain Baseline and Week 24 values.
Time Frame
A4091026: Baseline, A4091040: Week 24
Secondary Outcome Measure Information:
Title
Change From A4091026 (NCT00863772) Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) at Week 24
Description
NIS-LL:assess muscle weakness, reflexes, sensation;scored separately for left, right limbs. Components of muscle weakness (hip and knee flexion,hip and knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors) scored on scale 0(normal) to 4(paralysis),higher score=greater weakness. Components of reflexes(quadriceps femoris,triceps surae);sensation (touch pressure,pin-prick,vibration,joint position) scored 0=normal,1=decreased, or 2=absent. NIS-LL score: sum of scores of NIS items 17-24, 28-29 and 34-37. Total possible NIS-LL score range 0-88,high score=more impairment.
Time Frame
A4091026: Baseline, A4091040: Week 24
Title
Change From A4091026 (NCT00863772) Baseline in Neuropathy Impairment Score (NIS) at Week 24
Description
NIS: 74 items, assess muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0-244, higher score=greater impairment.
Time Frame
A4091026: Baseline, A4091040: Week 24
Title
Change From A4091026 (NCT00863772) Baseline in Neuropathy Symptoms and Change (NSC) Score at Week 24
Description
NSC score is the number of the 38 symptom questions where the participants indicated experiencing the symptom to any severity. Total score range: 0 to 38 where higher score indicated more symptoms.
Time Frame
A4091026: Baseline, A4091040: Week 24
Other Pre-specified Outcome Measures:
Title
Change From A4091026 (NCT00863772) Baseline in 5 Nerve Conduction Tests, Normal Deviate (5NC [nd]) Score at Week 24
Description
5NC (nd) score included five NCS attributes: peroneal MNDL, CMAP, MNCV; tibial MNDL; sural SNAP. Values of attributes scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as nd score based on standard normal distribution. For CMAP, MNCV, SNAP: score <0 indicated worse and >0 indicated better response; for peroneal,tibial MNDL: score >0 indicated worse and <0 indicated better response, as compared to normal matched population. For CMAP, MNCV, SNAP: score change <0 indicated worsening and >0 indicated improvement; for peroneal,tibial MNDL: score change >0 indicated worsening and <0 indicated improvement, as compared to baseline. Total score calculated as sum of each NCS attribute. Total score >0 indicated worse and <0 indicated better response as compared to normal matched population. Total score change >0 indicated worsening and <0 indicated improvement as compared to baseline.
Time Frame
A4091026: Baseline, A4091040: Week 24
Title
Change From A4091026 (NCT00863772) Baseline in Heart Rate-Deep Breathing, Normal Deviate (HRdb, [nd]) Score at Week 24
Description
HRdb test was used to evaluate the effect of treatment on autonomic function. Participant took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as normal deviates. Score <0 indicated worse response and >0 indicated better response as compared to normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Measurements were collected twice and highest nd score was selected at each NV. Mean of the selected measurements was calculated to obtain Baseline and Week 24 values.
Time Frame
A4091026: Baseline, A4091040: Week 24
Title
Change From A4091026 (NCT00863772) Baseline in Intraepidermal Nerve Fiber Density (IENF) at Week 24
Description
IENF density was quantified in 3 millimeter (mm) immunostained (PGP 9.5 immunohistochemical staining) skin punch biopsies taken from the distal end of the leg, 10 centimeter (cm) above the lateral malleolus, within the territory of the sural nerve, containing epidermis and superficial dermis to evaluate amount of small diameter nerve fibers. Skin biopsies were taken from normal appearing skin and skin having local scar, signs of trauma, ulceration, or active dermatologic process were avoided.
Time Frame
A4091026: Baseline, A4091040: Week 24
Title
Change From A4091026 (NCT00863772) Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Domain Scores at Week 8, 16, 24 and 32
Description
WOMAC Index: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items), and physical function (17 items) in participants with osteoarthritis of the index hip or index knee. Each question was assessed on Numeric Rating Scale (NRS) as 0(none) to 10(extreme).Total possible domain score was calculated as the mean of the score for each domain questions. Score range:0-10,high scores=high pain/stiffness/difficulty in physical activity.
Time Frame
A4091026: Baseline, A4091040: Week 8, 16, 24, 32
Title
Change From A4091026 (NCT00863772) Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 8, 16, 24 and 32
Description
PGA: Participants answered the following question: "Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today?" Participants rated their condition using a 5-point Likert scale. Score range: 1 to 5. 1: Very Good (asymptomatic and no limitation of normal activities); 2: Good (mild symptoms and no limitation of normal activities); 3: Fair (moderate symptoms and limitation of some normal activites); 4: Poor (severe symptoms and inability to carry out most normal activities); 5: Very Poor (very severe symptoms which are intolerable and inability to carry out all normal activities).
Time Frame
A4091026: Baseline, A4091040: Week 8, 16, 24, 32
Title
Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response
Description
OMERACT-OARSI response: >=50 percent (%) improvement from A4091026 (NCT00863772) baseline and absolute change from A4091026 (NCT00863772) baseline of >=2 units at week of interest in WOMAC pain or physical function subscales, or at least 2 of the following 3 being true: >=20% improvement from A4091026 (NCT00863772) baseline and absolute change from A4091026 (NCT00863772) baseline of >=1 unit at week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score: 0-10, higher score=higher pain/difficulty).
Time Frame
Week 8, 16, 24
Title
Change From A4091026 (NCT00863772) Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 8, 16 and 24
Description
WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items) and physical function (17 items) in participants with osteoarthritis of knee or hip. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher score indicates worse response. Change from baseline <0 indicates an improvement.
Time Frame
A4091026: Baseline, A4091040: Week 8, 16, 24
Title
Percentage of Participants With at Least 30%, 50%, 70% and 90% Reduction From A4091026 (NCT00863772) Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
Description
The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) during the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.
Time Frame
Week 8, 16, 24, 32
Title
Percentage of Participants With Improvement of At Least 2 Points From A4091026 (NCT00863772) Baseline in Patient's Global Assessment (PGA) of Osteoarthritis
Description
PGA: Participants answered the following question: "Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today?" Participants rated their condition using a 5-point Likert scale. Score range: 1 to 5. 1: Very Good (asymptomatic and no limitation of normal activities); 2: Good (mild symptoms and no limitation of normal activities); 3: Fair (moderate symptoms and limitation of some normal activites); 4: Poor (severe symptoms and inability to carry out most normal activities); 5: Very Poor (very severe symptoms which are intolerable and inability to carry out all normal activities).
Time Frame
Week 8, 16, 24, 32
Title
Change From A4091026 (NCT00863772) Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 24
Description
SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and mental health. The total score for each domain is scaled 0-100 (100 = highest level of functioning). Change from baseline >0 indicates an improvement.
Time Frame
A4091026: Baseline, A4091040: Week 24
Title
Change From A4091026 (NCT00863772) Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 24
Description
SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and mental health. Total score for each aspect were scaled 0-100 (100=highest level of functioning). For obtaining physical and mental component scores, z-score for each scale = (observed score -mean score for general 1990 United States [US] population)/corresponding standard deviation. The 2 component scores were obtained by multiplying each aspect z-score by physical or mental factor score coefficient (1990 general US population) and summing the eight products. Component scores indicated how many standard deviations higher (in case of positive z-score [better functioning])/lower (in case of negative z-score [worse functioning]) participant's value was relative to the mean of the reference population. Change from baseline >0 indicates an improvement.
Time Frame
A4091026: Baseline, A4091040: Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must consent in writing to participate in the study.
Patients must be 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 have participated in the A4091026 study.
Exclusion Criteria:
Withdrawn from the A4091026 study for an adverse event or serious adverse event.
Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to be pregnant during the course of clinical study.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
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
Jem Research, LLC
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Medical Specialists of the Palm Beaches
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Clinical Physiology Associates, Clinical Study Center
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33916
Country
United States
Facility Name
Harris Bonnette, MD
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33919
Country
United States
Facility Name
Arthritis & Rheumatic Care Center
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Miami Research Associates
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Neuroscience Consultants, LLC
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Asheville Imaging
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Biltmore Medical Associates
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Clinical Study Center of Asheville, LLC
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28803
Country
United States
Facility Name
Asheville Neurology
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28806-2287
Country
United States
Facility Name
Ohio Research Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623
Country
United States
Facility Name
Blair Neurologic Associates
City
Altoona
State/Province
Pennsylvania
ZIP/Postal Code
16601
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Coastal Carolina Research Center in Goose Creek
City
Goose Creek
State/Province
South Carolina
ZIP/Postal Code
29445
Country
United States
Facility Name
Tidewater Neurology
City
Goose Creek
State/Province
South Carolina
ZIP/Postal Code
29445
Country
United States
Facility Name
Neurodiagnostic Laboratories of San Antonio, Inc
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Radiant Research, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4091040&StudyName=Long-Term%20Study%20Of%20The%20Safety%20Of%20Tanezumab%20In%20Arthritis%20Patients
Description
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Learn more about this trial
Long-Term Study Of The Safety Of Tanezumab In Arthritis Patients
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