Tanezumab and Nerve Function In Arthritis Patients

Change From Baseline in Neuropathy Impairment Score - Lower Limbs [NIS (LL)] at Week 24

NIS-LL: assess muscle weakness, reflexes, sensation; scored separately for left and 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.

Time frame: Baseline, Week 24

Change From 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 are 24 items and scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes and sensation are 13 items and scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0 to 244, higher score = greater impairment.

Time frame: Baseline, Week 24

Change From 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. A change from Baseline \> 0 indicated some symptoms of peripheral neuropathy.

Time frame: Baseline, Week 24

Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: ITT Analysis Set

Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the two NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Peroneal Compound Muscle Action Potential Amplitude (CMAP) Score at Week 24: PPAS

Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: ITT Analysis Set

Peroneal motor nerve conduction velocity (in meters/second) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Peroneal Motor Nerve Conduction Velocity (MNCV) Score at Week 24: PPAS

Peroneal motor nerve conduction velocity (in meters/second) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set

Peroneal motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Peroneal Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS

Peroneal motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: ITT Analysis Set

Tibial motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Tibial Motor Nerve Distal Latency (MNDL) Score at Week 24: PPAS

Tibial motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (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 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: ITT Analysis Set

Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (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. A score \<0 indicated worse response and \>0 indicated better response than the normal matched population. A change \<0 indicated worsening and \>0 indicated improvement compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Sural Sensory Nerve Action Potential Amplitude (SNAP) Score at Week 24: PPAS

Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (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. A score \<0 indicated worse response and \>0 indicated better response than the normal matched population. A change \<0 indicated worsening and \>0 indicated improvement compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: ITT Analysis Set

HRdb test was used to evaluate the effect of treatment on autonomic function. Participants took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as a normal deviates. Score \<0 indicated worse response and \>0 indicated better response as compared to normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Measurements of HRdb were collected twice and highest nd score was selected at each NV. Mean of the 2 selected NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Heart Rate Deep Breathing [HRdb] at Week 24: PPAS

HRdb test was used to evaluate the effect of treatment on autonomic function. Participants took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as a normal deviates. Score \<0 indicated worse response and \>0 indicated better response as compared to normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Measurements of HRdb were collected twice and highest nd score was selected at each NV. Mean of the 2 selected NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in 5 Nerve Conduction Test - Normal Deviate [5NC (nd)] at Week 24: ITT Analysis Set

5NC (nd) score included 5 NCS attributes: peroneal MNDL, CMAP, MNCV, tibial MNDL and sural SNAP. Values of attributes scored as percentiles (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. Total score calculated as sum of each NCS attribute. Total score \>0 indicated worse and \<0 indicated better response as compared to normal matched population. Total score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in 5 Nerve Conduction Test - Normal Deviate (5NC [nd]) at Week 24: PPAS

5NC (nd) score included 5 NCS attributes: peroneal MNDL, CMAP, MNCV, tibial MNDL and sural SNAP. Values of attributes scored as percentiles (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. Total score calculated as sum of each NCS attribute. Total score \>0 indicated worse and \<0 indicated better response as compared to normal matched population. Total score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline.2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Change From Baseline in Protein Gene Product (PGP) 9.5-Positive Intraepidermal Epidermal Nerve Fiber (IENF) Density at Week 24

IENF density was quantified in 3 millimeter (mm) immunostained (PGP 9.5-immunohistochemical staining) skin punch biopsies taken from the distal end of the leg, 10 centimeter (cm) above the lateral malleolus, within the territory of the sural nerve, containing epidermis and superficial dermis to evaluate amount of small diameter nerve fibers. Skin biopsies were taken from normal appearing skin and skin having local scar, signs of trauma, ulceration, or active dermatologic process were avoided.

Time frame: 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

WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) 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 indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.

Time frame: 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

WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint (knee or hip) 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 indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function.

Time frame: Baseline, Weeks 8, 16, and 24

Change From Baseline in the Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 8, 16, and 24

Participants answered: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants rated their condition using a 5-point scale where 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). Higher score indicated severe condition.

Time frame: Baseline, Weeks 8, 16, and 24

Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response

OMERACT-OARSI response: \>=50 percent (%) improvement from baseline and absolute change from baseline of \>=2 units 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 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).

Time frame: 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

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint ( knee or hip) in the past 48 hours. It is calculated as the mean of the scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.

Time frame: 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

Participants answered: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants rated their condition using a 5-point scale where 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). Higher score indicated severe condition.

Time frame: 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

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) 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 indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. Participants with specified reduction (as percent) from baseline at Week 16 are reported.

Time frame: 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

Participants assessed daily average index joint pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Higher score indicated greater pain.

Time frame: 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

The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 2 individual questions scored on NRS of 0 to 10, with higher scores indicating more stiffness. Total score range for WOMAC stiffness subscale score is 0 to 10, where higher scores indicate more stiffness. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip).

Time frame: 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

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 to 10, where higher score indicates worse response. Change from baseline \<0 indicates an improvement.

Time frame: 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

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 indicated greater pain. Change from baseline \<0 indicated an improvement.

Time frame: 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

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. Higher score indicated greater pain. Change from baseline \<0 indicates an improvement.

Time frame: 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

SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and mental health. The total score for each domain is scaled 0-100 (100 = highest level of functioning). Change from baseline \>0 indicates an improvement.

Time frame: 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

SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and mental health. Total score for each aspect were scaled 0-100(100=highest level of functioning). For obtaining physical and mental component scores, z-score for each scale=(observed score - mean score for general 1990 United States \[US\] population)/corresponding standard deviation. The 2 component scores were obtained by multiplying each aspect z-score by physical or mental factor score coefficient (1990 general US population) and summing the eight products. Component scores indicated how many standard deviations higher (in case of positive z-score \[better functioning\])/lower (in case of negative z-score \[worse functioning\]) participant's value was relative to the mean of the reference population. Change from baseline \>0 indicates an improvement.

Time frame: Baseline, Week 24

Number of Participants With Rescue Medication Usage

In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.

Time frame: Week 8, 16, 24

Number of Days With Rescue Medication Usage

In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Result reported is number of days of rescue medication use in each week, and ranges from 0 to 7.

Time frame: Weeks 8, 16, and 24

Amount of Rescue Medication Used

In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Results reported is total dose of acetaminophen (in mg) for each week.

Time frame: Weeks 8, 16, and 24

Number of Participants With Anti-Drug Antibody (ADA)

Human serum samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semiquantitative enzyme-linked immunosorbent assay (ELISA). Same participant may have positive ADA result at more than 1 time point.

Time frame: pre-dose on Day 1 (Baseline), Week 8, 16, 24, 32

Plasma Trough Concentration of Tanezumab

Plasma trough concentration of tanezumab was measured using a validated, sensitive and specific enzyme-linked immunosorbent assay (ELISA).

Time frame: pre-dose on Day 1 (Baseline), Weeks 8, 16, 24, and 32

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was 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. AEs included both serious AEs and non-serious AEs.

Time frame: 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)