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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER, LONG-TERM SAFETY STUDY 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
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Withdrawn from the A4091026 study for an adverse event or serious adverse event.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.

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 5 mg<br> | Biological: Tanezumab<br>* IV, 5 mg dose, q 8 weeks, for up to 80 weeks<br>|
| Experimental: Tanezumab 10 mg<br> | Biological: Tanezumab<br>* IV, 10 mg dose, q 8 weeks, for up to 80 weeks<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* IV, q 8 weeks, for up to 80 weeks<br>|

What is the study measuring?
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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 |