A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF TANEZUMAB ON PERIPHERAL NERVE FUNCTION IN PATIENTS WITH OSTEOARTHRITIS.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 220
- 试验地点
- 192
- 主要终点
- Change From Baseline in 5 Nerve Conduction Tests-Normal Deviate and Heart Rate Deep Breathing-Normal Deviate (5NC [nd] + HRdb [nd]) Composite Score at Week 24: Intent to Treat (ITT) Analysis Set
研究概览
简要总结
Tanezumab reduces pain of osteoarthritis without affecting how nerve impulses are transmitted in sensory nerves.
详细描述
This study was terminated on 16 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI less or equal to 39 kg/m2
- •Osteoarthritis (arthritis) of the knee or hip with pain score that qualifies
- •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 consent in writing to participate in the study.
排除标准
- •Untreated, uncontrolled diseases,
- •Unwilling or unable to discontinue the use of prohibited medications, including other pain medications, during the screening period and during the study,
- •Significant cardiac disease within the past 6 months
- •Significant neurological disease (e.g. peripheral neuropathy, multiple sclerosis, stroke) or signs of neuropathy at screening
- •Known bleeding disorder or anticoagulation therapy
- •Planned surgery during the study period
- •History of alcoholism or drug abuse in the past 2 years
- •Unable to use acetaminophen
- •Use of a biologic (including live vaccines, with the exception of Flumist) within the past 3 months
- •Allergic reaction to a biologic or an antibody in the past
- •Disqualifying laboratory values, including Hepatitis B or C, HIV or drug test
- •Cancer in the past 5 years. Basal cell or squamous cell carcinoma are okay.
- •Medical condition that may interfere with study endpoints or safety of the subject as determined by the investigator.
结局指标
主要结局
Change From Baseline in 5 Nerve Conduction Tests-Normal Deviate and Heart Rate Deep Breathing-Normal Deviate (5NC [nd] + HRdb [nd]) Composite Score at Week 24: Intent to Treat (ITT) Analysis Set
时间窗: Baseline, 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.
Change From Baseline in 5 Nerve Conduction Tests-Normal Deviate and Heart Rate Deep Breathing-Normal Deviate (5NC [nd] + HRdb [nd]) Composite Score at Week 24: Per Protocol Analysis Set (PPAS)
时间窗: Baseline, 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.
次要结局
- Change From Baseline in Neuropathy Impairment Score - Lower Limbs [NIS (LL)] at Week 24(Baseline, Week 24)
- Change From Baseline in Neuropathy Impairment Score (NIS) at Week 24(Baseline, Week 24)
- Change From Baseline in Neuropathy Symptoms and Change (NSC) Score at Week 24(Baseline, Week 24)
- Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: ITT Analysis Set(Baseline, Week 24)
- Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: PPAS(Baseline, Week 24)
- Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: ITT Analysis Set(Baseline, Week 24)
- Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: PPAS(Baseline, Week 24)
- Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set(Baseline, Week 24)
- Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS(Baseline, Week 24)
- Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set(Baseline, Week 24)
- Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS(Baseline, Week 24)
- Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: ITT Analysis Set(Baseline, Week 24)
- Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: PPAS(Baseline, Week 24)
- Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: ITT Analysis Set(Baseline, Week 24)
- Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: PPAS(Baseline, Week 24)
- Change From Baseline in 5 Nerve Conduction Test - Normal Deviate [5NC (nd)] at Week 24: ITT Analysis Set(Baseline, Week 24)
- Change From Baseline in 5 Nerve Conduction Test - Normal Deviate (5NC [nd]) at Week 24: PPAS(Baseline, Week 24)
- Change From Baseline in Protein Gene Product (PGP) 9.5-Positive Intraepidermal Epidermal Nerve Fiber (IENF) Density at Week 24(Baseline, Week 24)
- Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 8, 16, and 24(Baseline, Weeks 8, 16, and 24)
- Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 8, 16, and 24(Baseline, Weeks 8, 16, and 24)
- Change From Baseline in the Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 8, 16, and 24(Baseline, Weeks 8, 16, and 24)
- Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response(Weeks 8, 16, and 24)
- Percentage of Participants With At Least 30%, 50%, 70% and 90% Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score(Weeks 8, 16, and 24)
- Percentage of Participants With Improvement of At Least 2 Points From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis(Weeks 8, 16, and 24)
- Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score(Week 16)
- Change From Baseline in Average Pain Score in the Index Knee/Hip Joint at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 16, 17, 18, 19, 20, 21, 22, 23, and 24(Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 16, 17, 18, 19, 20, 21, 22, 23, and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 8, 16, and 24(Baseline, Weeks 8, 16, and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 8, 16, and 24(Baseline, Weeks 8, 16, and 24)
- Change From Baseline in WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 8, 16, and 24(Baseline, Weeks 8, 16, and 24)
- Change From Baseline in WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 8, 16, and 24(Baseline, Weeks 8, 16, and 24)
- Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 24(Baseline, Week 24)
- Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 24(Baseline, Week 24)
- Number of Participants With Rescue Medication Usage(Week 8, 16, 24)
- Number of Days With Rescue Medication Usage(Weeks 8, 16, and 24)
- Amount of Rescue Medication Used(Weeks 8, 16, and 24)
- Number of Participants With Anti-Drug Antibody (ADA)(pre-dose on Day 1 (Baseline), Week 8, 16, 24, 32)
- Plasma Trough Concentration of Tanezumab(pre-dose on Day 1 (Baseline), Weeks 8, 16, 24, and 32)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline through 112 days after last Intravenous dose of Investigational product to last participant treated with study medication on study (up to Week 32 after last IV dose of investigational product to last participant treated))