Safety Extension Study Of Tanezumab When Administered By Subcutaneous Injection To Patients With Osteoarthritis

Study Overview
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Brief Summary
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An evaluation of the long term safety of tanezumab when administered by subcutaneous injection every 8 weeks for up to 64 weeks

Detailed Description
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This study was terminated on 29 September 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.

Official Title
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A PHASE 3, MULTICENTER, RANDOMIZED, LONG TERM STUDY OF THE SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE

Conditions
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Osteoarthritis

Intervention / Treatment
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* Biological: Tanezumab
* Biological: Tanezumab
* Biological: Tanezumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have participated in specific Phase 3 parent study Exclusion Criteria: Failed screening for parent study, pregnant women, lactating mothers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tanezumab 10 mg<br> | Biological: Tanezumab<br>* Tanezumab 10 mg administered by subcutaneous injection every 8 weeks for up to 7 injections<br>|
| Experimental: Tanezumab 5 mg<br> | Biological: Tanezumab<br>* Tanezumab 5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections<br>|
| Experimental: Tanezumab 2.5 mg<br> | Biological: Tanezumab<br>* Tanezumab 2.5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug, up to early termination (Day 107) that were absent before treatment in this study or that worsened relative to pretreatment state. | Baseline up to Early Termination (Day 107) | 
| Number of Participants With Clinically Significant Laboratory Abnormalities | Laboratory examination included blood chemistry, hematology and urinalysis. Reported results were to include abnormal laboratory findings without regard to baseline abnormality. | Baseline up to Early Termination (Day 107) | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Bazett's formula (QTcB), QT interval corrected using Fredericia's formula (QTcF), RR interval and heart rate (HR). | Baseline up to Early Termination (Day 107) | 
| Number of Participants With Neurologic Examination Abnormalities | Neurologic examination assessed the strength of groups of muscles of the head and neck, upper limbs and lower limbs, deep tendon reflexes and sensation (tactile, vibration, joint position sense and pin prick) of index fingers and great toes. | Baseline up to Early Termination (Day 107) | 
| Number of Participants With Anti-Drug (Tanezumab) Antibody (ADA) | Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA). | Baseline up to Early Termination (Day 107) | 
| Number of Participants With Injection Site Reactions | Injection site reactions included: erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection has been administered. | Baseline up to Early Termination (Day 107) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 | The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint in 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 indicated higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicated higher pain. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 | The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on a NRS of 0 to 10, where higher scores indicated worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 | PGA: Participants answered the following question: Considering all the ways your osteoarthritis (OA) in your knee affects you, how are you doing today? Participants rated their condition by using a 5-point Likert scale: 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 activities); 4) Poor (severe symptoms and inability to carry out most normal activities); and 5) Very Poor (very severe symptoms which are intolerable and inability to carry out all normal activities). | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Percentage of Participants With Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International (OMERACT-OARSI) Response | OMERACT-OARSI response: >=50 percent (%) improvement from baseline and absolute change from baseline of >=2 units at Week of interest in WOMAC pain or physical function subscale, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from 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). | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Percentage of Participants With At Least 30 Percent (%), 50%, 70% and 90% Reduction 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 in the past 48 hours. It was 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 indicated higher pain. Total score range for WOMAC pain subscale score was 0 to 10, where higher scores indicated higher pain. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Number of Participants With Cumulative Reduction From 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 in the past 48 hours. It was 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 indicated higher pain. Total score range for WOMAC pain subscale score was 0 to 10, where higher scores indicated higher pain. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Percentage of Participants With Improvement of At Least (>=) 2 Point in Patient Global Assessment (PGA) of Osteoarthritis | PGA: Participants answered the following question: Considering all the ways your OA in your joint affects you, how are you doing today? Participants rated their condition by using a 5-point Likert scale: 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 activities); 4) Poor (severe symptoms and inability to carry out most normal activities); and 5) Very Poor (very severe symptoms which are intolerable and inability to carry out all normal activities). | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 | The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced in the index joint in the past 48 hours. It was calculated as the mean of the scores from the 2 individual questions scored on NRS of 0 to 10; where higher scores indicated more stiffness. Total score range for WOMAC stiffness subscale score is 0 to 10, where higher scores indicated more stiffness. Stiffness is defined as a sensation of decreased ease in movement of the index joint. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 | 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. WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher score indicated worse response. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Change From Baseline in WOMAC Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 | Participants answered: How much pain have you had when walking on a flat surface? Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Change From Baseline in WOMAC Pain Subscale Item (Pain When Going Up or Down Stairs) at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 | Participants answered: How much pain have you had when going up or down stairs? Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. | Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 | 
| Time to Discontinuation Due to Lack of Efficacy |  | Baseline up to Week 64 | 
| Number of Participants Who Received Concomitant Analgesic Medication for Osteoarthritis Treatment | Permissible concomitant analgesic medications included Food and Drug Administration (FDA) approved opioids, topical analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), capsaicin products, oral/injectable corticosteroids and viscosupplementation (for example, hyaluronan) and were to be prescribed as per investigator's discretion. | Baseline up to Day 107 (Early Termination) | 
| Days Per Week of Concomitant Analgesic Medication Usage for Osteoarthritis Treatment | Permissible concomitant analgesic medications included Food and Drug Administration (FDA) approved opioids, topical analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), capsaicin products, oral/injectable corticosteroids and viscosupplementation (for example, hyaluronan) and were to be prescribed as per investigator's discretion. | Baseline up to Week 64 | 
| Tanezumab Plasma Concentration |  | Pre-dose on Week 8, 24, 40; Week 56, 64 | 
| Nerve Growth Factor (NGF) Serum Concentration | Serum samples were analyzed for determining total NGF concentration. Total NGF was analyzed using a validated, sensitive, and specific immune-affinity enrichment liquid chromatography tandem mass spectrometric (IA/LC/MS/MS) method. | Pre-dose on Week 8, 24, 40; Week 56, 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Musculoskeletal Diseases, Joint Diseases, Arthritis, Rheumatic Diseases