Extension Study Of Tanezumab In Osteoarthritis

Study Overview
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Brief Summary
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Safety extension study of Phase 3 Osteoarthritis trials with Tanezumab

Detailed Description
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This study was terminated on 27 October 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 TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP

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 previous (specific) Phase 3 trials of Tanezumab in osteoarthritis Exclusion Criteria: Willing to comply with scheduled visits and treatment plan Is medically fit to participate in the trial in the judgement of the Investigator

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>Tanezumab 10 mg | Biological: tanezumab<br>* Tanezumab 10 mg<br>* Other names: RN624;|
| Experimental: Tanezumab 5 mg<br>Tanezumab 5 mg | Biological: tanezumab<br>* Tanezumab 5 mg<br>* Other names: RN624;|
| Experimental: Tanezumab 2.5 mg<br>Tanezumab 2.5 mg | Biological: tanezumab<br>* Tanezumab 2.5 mg<br>* Other names: RN624;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) | AE:any untoward medical occurrence in participant who received study medication without regard to possibility of causal relationship. SAE:an AE resulting in any of 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 medication and up to 112 days after last dose that were absent before treatment in this study or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs. | A4091016: Baseline (Day 1) up to 112 days after last dose of study medication (up to Week 80) | 
| Number of Participants With Abnormal Laboratory Findings | Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(<)0.8*lower limit of normal(LLN),MCV,MCH,MCHC<0.9*LLN or >1.1*ULN,platelet:<0.5*LLN or >1.75*upper limit of normal(ULN),white blood cell(WBC):<0.6*LLN or >1.5*ULN,lymphocyte,neutrophil,total neutrophil:<0.8*LLN or>1.2*ULN,basophil,eosinophil,monocyte:>1.2*ULN;total,direct bilirubin>1.5*ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,LDH,alkaline phosphatase:> 3.0*ULN,total protein,albumin:<0.8*LLN or >1.2*ULN;blood urea nitrogen,creatinine:>1.3*ULN,uric acid>1.2*ULN;cholesterol,triglycerides>1.3*ULN;sodium <0.95*LLN or >1.05*ULN,potassium,chloride,calcium,magnesium,bicarbonate:<0.9*LLN or >1.1*ULN,phosphate<0.8*LLN or>1.2*ULN;glucose <0.6*LLN or >1.5*ULN,glycosylated Hgb >1.3*ULN,creatine kinase>2.0*ULN;urine(specific gravity <1.003or>1.030,pH <4.5or>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals>=1,RBC,WBC >1.5*ULN,epithelial cell>=6,casts,hyaline cast>1,bacteria>20). | A4091016: Day 1 up to Week 80 | 
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings | Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's formula (QTcF), QT interval corrected using the Bazett's formula (QTcB), RR interval and VR interval. Number of participants with clinically significant abnormal ECG findings were judged by investigator and reported as adverse events were presented. | A4091016: Baseline (Day 1) up to Week 80 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Parent Study Baseline in Neuropathy Impairment Score (NIS) at Week 4, 8, 16, 24, 32, 40, 48, 56, 64 and 72 | NIS constitutes sum of 37 standard items of neuromuscular examination used to assess muscle strength, reflexes and sensation. Each item is scored separately for left and right sides. Components of muscle weakness (24 items) scored on a scale: 0 (normal) to 4 (paralysis), with higher score=more weakness; components of reflexes and sensation (13 items) scored on a scale: 0= normal, 1= decreased or 2= absent. Total NIS score range 0 (no impairment) to 244 (maximum impairment), higher score = more impairment. Parent study baseline value calculated as average of pre-dose measurements of participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72 | 
| Number of Participants With Anti-drug Antibodies (ADA) for Tanezumab | Human serum anti-drug antibody (ADA) samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA). Same participant may have positive ADA result at more than 1 time point. | A4091016: Day 1, Week 16, 24, 40, 56, 72, 80 or Early Termination (ET: anytime till Week 80) | 
| Number of Participants With Clinically Significant Changes From Baseline to Week 80 in Physical Examination Findings | Physical examination included examination of following sites in addition to general examination: abdomen, ears, extremities, eyes, head, heart, musculoskeletal, neck, nose, skin, throat and thyroid. Clinically significant changes were judged by investigator. | Baseline (Day 1) up to Week 80 | 
| Number of Participants With Clinically Significant Abnormality in Vital Signs | Following parameters were analyzed for examination of vital signs: body temperature, blood pressure, heart rate and respiratory rate. Number of participants with clinically significant abnormality in vital signs were judged by investigator and reported as adverse events were presented. | A4091016: Baseline (Day 1) up to Week 80 | 
| Change From Parent Study Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104 | The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip joint during past 48 hours. The WOMAC pain score is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (minimum pain) to 10 (maximum pain), where higher scores indicate higher pain. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Change From Parent Study Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104 | The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee or hip joint during past 48 hours. The WOMAC physical function score is calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse function. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Change From Parent Study Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104 | Participants answered: Considering all the ways your osteoarthritis in your knee/hip affects you, how are you doing today? Participants responded by using a 5-point scale where 1 = very good and 5 = very poor. Higher scores indicate worse condition. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response | OMERACT-OARSI response:>=50 percent(%) improvement from parent study baseline and absolute change from parent study baseline of >=2 units at given week in WOMAC pain or physical function subscale or >=20% improvement from parent study baseline and absolute change from parent study baseline of >=1 unit at given week in at least 2 of following 3 items: 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). | A4091016: Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104 | 
| Percentage of Participants With at Least 30%, 50%, 70% and 90% Reduction From Parent Study Baseline in 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 index knee or hip joint during past 48 hours. The WOMAC pain score is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (minimum pain) to 10 (maximum pain), where higher scores indicate higher pain. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Number of Participants With Cumulative Reduction From Parent Study Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16, 24, 56 and 104 | The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip joint during past 48 hours. The WOMAC pain score is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (minimum pain) to 10 (maximum pain), where higher scores indicate higher pain. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 16, 24, 56, 104 | 
| Percentage of Participants With Improvement of at Least 2 Points From Parent Study Baseline in Patient Global Assessment (PGA) of Osteoarthritis | Participants answered: Considering all the ways your osteoarthritis in your knee/hip affects you, how are you doing today? Participants responded by using a 5-point scale where 1 = very good and 5 = very poor. Higher scores indicated worse pain. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Change From Parent Study Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104 | WOMAC stiffness subscale: questionnaire used to assess amount of stiffness experienced due to osteoarthritis in index joint during past 48 hours. The WOMAC stiffness score is calculated as mean of scores from 2 individual questions scored on NRS of 0 (minimum stiffness) to 10 (maximum stiffness), higher scores indicate higher stiffness. Total score range for WOMAC stiffness subscale score =0 (minimum stiffness) to 10 (maximum stiffness), higher scores indicate higher stiffness. Stiffness is defined as sensation of decreased ease in movement of knee/hip. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Change From Parent Study Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104 | 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 (minimum difficulty) to 10 (maximum difficulty), where higher score indicates worse response. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Change From Parent Study Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Downstairs at Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104 | Participants answered: How much pain have you had going up or down the stairs? Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. Higher score indicates more pain. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Change From Parent Study Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Week 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104 | 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. Higher score indicates more pain. Parent study baseline value calculated as average of pre-dose measurements of the participants from study A4091011, A4091014, A4091015 and A4091018. | Baseline of the parent study (A4091011, A4091014, A4091015, A4091018); A4091016: Week 4, 8, 16, 24, 32, 40, 48,56, 64, 72, 80, 88, 96, 104 | 
| Percentage of Participants Who Used Concomitant Analgesic Medication | United States Food and Drug Administration (FDA) approved analgesics (over-the-counter or prescription) were permitted as concomitant medications to relieve the pain of osteoarthritis. These medications included opioids, topical analgesics, non-steroidal anti inflammatory drugs (NSAIDs), capsaicin products, oral/injectable corticosteroids and viscosupplementation (hyaluronan) and were prescribed as per investigator's discretion. | Week 1-4, 5-8, 9-16, 17-24, 25-32, 33-40, 41-48, 49-56, 57-64, 65-72, 73-80, 81-88, 89-96, 97-104, 105-112 | 
| Days Per Week of Concomitant Analgesic Medication Usage | FDA approved analgesics (over-the-counter or prescription) were permitted as concomitant medications to relieve the pain of osteoarthritis. These medications included opioids, topical analgesics, NSAIDs, capsaicin products, oral/injectable corticosteroids and viscosupplementation (hyaluronan) and were prescribed at the discretion of the investigator. | Week 1-4, 5-8, 9-16, 17-24, 25-32, 33-40, 41-48, 49-56, 57-64, 65-72, 73-80, 81-88, 89-96, 97-104, 105-112 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tanezumab OA arthritis