Safety Extension Study Of Tanezumab When Administered By Subcutaneous Injection To Patients With Osteoarthritis
- Conditions
- Osteoarthritis
- Interventions
- Biological: Tanezumab
- Registration Number
- NCT01127893
- Lead Sponsor
- Pfizer
- Brief Summary
An evaluation of the long term safety of tanezumab when administered by subcutaneous injection every 8 weeks for up to 64 weeks
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
- Must have participated in specific Phase 3 parent study
- Failed screening for parent study, pregnant women, lactating mothers
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tanezumab 5 mg Tanezumab - Tanezumab 10 mg Tanezumab - Tanezumab 2.5 mg Tanezumab -
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to Early Termination (Day 107) 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.
Number of Participants With Anti-Drug (Tanezumab) Antibody (ADA) Baseline up to Early Termination (Day 107) 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).
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities Baseline up to Early Termination (Day 107) 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).
Number of Participants With Clinically Significant Laboratory Abnormalities Baseline up to Early Termination (Day 107) Laboratory examination included blood chemistry, hematology and urinalysis. Reported results were to include abnormal laboratory findings without regard to baseline abnormality.
Number of Participants With Neurologic Examination Abnormalities Baseline up to Early Termination (Day 107) 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.
Number of Participants With Injection Site Reactions Baseline up to Early Termination (Day 107) Injection site reactions included: erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection has been administered.
- Secondary Outcome Measures
Name Time Method Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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 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.
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 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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.
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 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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.
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 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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.
Percentage of Participants With Improvement of At Least (>=) 2 Point in Patient Global Assessment (PGA) of Osteoarthritis Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 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).
Number of Participants Who Received Concomitant Analgesic Medication for Osteoarthritis Treatment Baseline up to Day 107 (Early Termination) 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.
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 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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.
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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).
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 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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 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.
Percentage of Participants With Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International (OMERACT-OARSI) Response Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64 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).
Tanezumab Plasma Concentration Pre-dose on Week 8, 24, 40; Week 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 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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.
Nerve Growth Factor (NGF) Serum Concentration Pre-dose on Week 8, 24, 40; Week 56, 64 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.
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 Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 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.
Time to Discontinuation Due to Lack of Efficacy Baseline up to Week 64 Days Per Week of Concomitant Analgesic Medication Usage for Osteoarthritis Treatment Baseline up to Week 64 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.
Trial Locations
- Locations (1)
Triwest Research Associates
🇺🇸La Mesa, California, United States