Long-Term Study Of The Safety Of Tanezumab In Arthritis Patients

A PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER, LONG-TERM SAFETY STUDY OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP

Tanezumab, administered for up to 1 1/2 years, reduces the pain of osteoarthritis without affecting how nerve impulses are transmitted in sensory nerves

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis
• Intervention / Treatment: Biological: Tanezumab; Biological: Tanezumab; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research, LLC
    • Atlantis, Florida, United States, 33462
      • Medical Specialists of the Palm Beaches
    • Fort Myers, Florida, United States, 33916
      • Clinical Physiology Associates, Clinical Study Center
    • Fort Myers, Florida, United States, 33919
      • Harris Bonnette, MD
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • Arthritis & Rheumatic Care Center
    • South Miami, Florida, United States, 33143
      • Neuroscience Consultants, LLC
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Imaging
    • Asheville, North Carolina, United States, 28801
      • Biltmore Medical Associates
    • Asheville, North Carolina, United States, 28803
      • Clinical Study Center of Asheville, LLC
    • Asheville, North Carolina, United States, 28806-2287
      • Asheville Neurology
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Ohio Research Center
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16601
      • Blair Neurologic Associates
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • South Carolina
    • Goose Creek, South Carolina, United States, 29445
      • Coastal Carolina Research Center in Goose Creek
    • Goose Creek, South Carolina, United States, 29445
      • Tidewater Neurology
  • Texas
    • San Antonio, Texas, United States, 78229
      • Radiant Research, Inc.
    • San Antonio, Texas, United States, 78229
      • Neurodiagnostic Laboratories of San Antonio, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; IV, q 8 weeks, for up to 80 weeks
Experimental: Tanezumab 5 mg	Biological: Tanezumab; IV, 5 mg dose, q 8 weeks, for up to 80 weeks; Biological: Tanezumab; IV, 10 mg dose, q 8 weeks, for up to 80 weeks
Experimental: Tanezumab 10 mg	Biological: Tanezumab; IV, 5 mg dose, q 8 weeks, for up to 80 weeks; Biological: Tanezumab; IV, 10 mg dose, q 8 weeks, for up to 80 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	A4091026: Baseline, A4091040: Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	A4091026: Baseline, A4091040: Week 24
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.	A4091026: Baseline, A4091040: Week 24
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.	A4091026: Baseline, A4091040: Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From A4091026 (NCT00863772) Baseline in 5 Nerve Conduction Tests, Normal Deviate (5NC [nd]) Score at Week 24	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.	A4091026: Baseline, A4091040: Week 24
Change From A4091026 (NCT00863772) Baseline in Heart Rate-Deep Breathing, Normal Deviate (HRdb, [nd]) Score at Week 24	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.	A4091026: Baseline, A4091040: Week 24
Change From A4091026 (NCT00863772) Baseline in Intraepidermal Nerve Fiber Density (IENF) at Week 24	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.	A4091026: Baseline, A4091040: Week 24
Change From A4091026 (NCT00863772) Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Domain Scores at Week 8, 16, 24 and 32	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.	A4091026: Baseline, A4091040: Week 8, 16, 24, 32
Change From A4091026 (NCT00863772) Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 8, 16, 24 and 32	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).	A4091026: Baseline, A4091040: Week 8, 16, 24, 32
Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response	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).	Week 8, 16, 24
Change From A4091026 (NCT00863772) Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 8, 16 and 24	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.	A4091026: Baseline, A4091040: Week 8, 16, 24
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	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.	Week 8, 16, 24, 32
Percentage of Participants With Improvement of At Least 2 Points From A4091026 (NCT00863772) Baseline in Patient's Global Assessment (PGA) of Osteoarthritis	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).	Week 8, 16, 24, 32
Change From A4091026 (NCT00863772) Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 24	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.	A4091026: Baseline, A4091040: Week 24
Change From A4091026 (NCT00863772) Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 24	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.	A4091026: Baseline, A4091040: Week 24

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2010
• Primary Completion (Actual): November 11, 2010
• Study Completion (Actual): November 11, 2010

Study Registration Dates

• First Submitted: August 17, 2009
• First Submitted That Met QC Criteria: August 17, 2009
• First Posted (Estimate): August 18, 2009

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tanezumab
• Other Study ID Numbers: A4091040; NERVE FUNCTION EXTENSION STUDY (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.