A Long Term Study of the Safety of Tanezumab When Administered By Subcutaneous Injections

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00994890
• Collaborator: (none)
• Enrollment: 679
• Locations: 100
• Arms: 3
• Actual Duration (Months): 15.4
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will investigate the safety of three fixed dose levels of tanezumab (2.5 mg, 5 mg, and 10 mg) administered at an 8-week interval by subcutaneous injection multiple (7) times during the study treatment period.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee; Osteoarthritis, Hip	Drug: Tanezumab 2.5 mg; Drug: Tanezumab 5 mg; Drug: Tanezumab 10 mg	Phase 2

Detailed Description

Safety study of tanezumab in relief of osteoarthritis pain This study was terminated on 6 December 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 679 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: A MULTICENTRE, RANDOMIZED, DOUBLE-BLIND,LONG TERM STUDY OF THE SAFETY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP
• Actual Study Start Date: Nov 17, 2009
• Actual Primary Completion Date: Dec 7, 2010
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tanezumab 2.5 mg	Drug: Tanezumab 2.5 mg; Tanezumab 2.5 mg administered by subcutaneous injection every 8 weeks for a total of 7 injections administered over approximately 1 year; Other Names: Biological
Experimental: Tanezumab 5 mg	Drug: Tanezumab 5 mg; Tanezumab 5 mg administered by subcutaneous injection every 8 weeks for a total of 7 injections administered over approximately 1 year; Other Names: Biological
Experimental: Tanezumab 10 mg	Drug: Tanezumab 10 mg; Tanezumab 10 mg administered by subcutaneous injection every 8 weeks for a total of 7 injections administered over approximately 1 year; Other Names: Biological

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Baseline up to 112 days after last dose of study medication (up to 345 days)]

   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. Treatment-emergent are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

2. Number of Participants With Laboratory Abnormalities [Baseline to Week 50]

   Laboratory analysis included blood chemistry, hematology, urinalysis and pregnancy test.

3. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Baseline up to Week 50]

   All standard intervals (PR, QRS, QT, QT interval corrected for heart rate using Fridericia's formula [QTcF], QT interval corrected for heart rate using Bazett's formula [QTcB], RR intervals and heart rate) were analyzed. Participants with abnormal ECG findings reported as adverse events were presented.

4. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 2 [Baseline, Week 2]

   NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

5. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 4 [Baseline, Week 4]

   NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

6. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 8 [Baseline, Week 8]

   NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

7. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 16 [Baseline, Week 16]

   NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

8. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 24 [Baseline, Week 24]

   NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

9. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 32 [Baseline, Week 32]

   NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

10. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 40 [Baseline, Week 40]

    NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

11. Change From Baseline in Neuropathy Impairment Score (NIS) at Week 48 [Baseline, Week 48]

    NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.

12. Number of Participants With Clinically Significant Change From Baseline in Physical Findings [Baseline to Week 50]

    Physical examination included examination of abdomen, ears, extremities, eyes, head, heart, lungs, lymph nodes, neck, nose, skin, throat, thyroid, muscoskeletal, neurological and peripheral vascular system.

13. Number of Participants With Anti-Drug Antibody (ADA) at Day 1 [Day 1]

    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).

14. Number of Participants With Anti-Drug Antibody (ADA) at Week 8 [Week 8]

    Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative ELISA.

15. Number of Participants With Anti-Drug Antibody (ADA) at Week 24 [Week 24]

    Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative ELISA.

16. Number of Participants With Anti-Drug Antibody (ADA) at Week 50 [Week 50]

    Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative ELISA.

17. Number of Participants With Vital Sign Abnormalities [Baseline up to Week 50]

    Examination of vital signs included body temperature, systolic blood pressure, diastolic blood pressure, pulse rate and respiratory rate. Participants with abnormal vital sign findings reported as adverse events were presented.

18. Number of Participants With Injection-Site Reactions at Day 1 [Day 1]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

19. Number of Participants With Injection-Site Reactions at Week 2 [Week 2]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

20. Number of Participants With Injection-Site Reactions at Week 4 [Week 4]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

21. Number of Participants With Injection-Site Reactions at Week 8 [Week 8]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

22. Number of Participants With Injection-Site Reactions at Week 16 [Week 16]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

23. Number of Participants With Injection-Site Reactions at Week 24 [Week 24]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

24. Number of Participants With Injection-Site Reactions at Week 32 [Week 32]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

25. Number of Participants With Injection-Site Reactions at Week 40 [Week 40]

    Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).

Secondary Outcome Measures

1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or index hip during past 48 hours. It was calculated as 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.

2. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint and index hip during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on NRS of 0 to 10, with higher scores indicated worse function. Total score range for WOMAC physical function subscale score was 0 to 10, where higher scores indicated worse function.

3. Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 2, 4, 8,16, 24, 32, 40, 48 and 56 [Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   Participants answered: "Considering all the ways your osteoarthritis in your knee (or hip) affects you, how are you doing today?" Participants responded by using a 5-point scale where 1 = very good (no symptom and limitation of normal activities) and 5 = very poor (very severe symptoms and inability to carry out normal activities).

4. Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response [Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   OMERACT-OARSI response: greater than or equal to (>=) 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).

5. 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 [Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   Percentage of participants with at least 30%, 50%, 70% and 90% reduction from baseline in WOMAC pain subscale score are reported. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or index hip during past 48 hours. It was calculated as mean of the scores from the 5 individual questions scored on a 0 to 10 NRS, where higher scores indicated higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicated higher pain.

6. Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score [Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or index hip during past 48 hours. It is calculated as 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. Participants with specified reduction (as percent) from baseline at Week 16 are reported.

7. Percentage of Participants With Improvement of At Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis [Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   Participants answered: "Considering all the ways your osteoarthritis in your knee (or hip) affects you, how are you doing today?" Participants responded by using a 5-point scale where 1 = very good and 5 = very poor. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value.

8. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

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

9. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56]

   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. Each item was scored on a 0 to 10 NRS scale, where higher scores indicated higher pain/stiffness or worse function. WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranged from 0 to 10, where higher score indicated worse response.

10. Change From Baseline in WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56]

    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.

11. Change From Baseline in WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56]

    Participants answered: "How much pain have you had when going up or down the stairs?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain.

12. Time to Discontinuation Due to Lack of Efficacy [Baseline up to Week 50]

    Median time to discontinuation due to lack of efficacy was estimated using Kaplan-Meier method.

13. Number of Participants Who Discontinued Due to Lack of Efficacy [Baseline up to Week 50]

14. Percentage of Participants Who Used Concomitant Analgesic Medication [Week 2, 4, 8, 16, 24, 32, 40, 48, 56, 64]

    United States Food and Drug Administration (FDA) approved analgesics 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 and viscosupplementation (example, hyaluronan) and were prescribed at the discretion of the Investigator.

15. Days Per Week of Concomitant Analgesic Medication Usage [Week 2, 4, 8, 16, 24, 32, 40, 48, 56, 64]

    United States FDA-approved analgesics were permitted as concomitant medications to relieve the pain of OA. These medications included opioids, topical analgesics, NSAIDs, capsaicin products and viscosupplementation (example, hyaluronan) and were prescribed at the discretion of the Investigator.

Other Outcome Measures

1. Number of Participants With Subcutaneous Doses of Study Medication [Day 1 up to Week 24]

   Number of participants are reported based on the maximum number of subcutaneous doses of study medication received.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Osteoarthritis of the knee or hip based on American College of Rheumatology criteria with a radiographic (X ray) confirmation (a Kellgren Lawrence x-ray grade of ≥2);

Exclusion Criteria:

• Body mass index (BMI) of >39 kg/m2;

• Pregnancy or intent to become pregnant

• Planned surgical procedure during the duration of the study

• History of clinically significant cardiovascular, central nervous system or psychiatric disease

• Previous exposure to exogenous NGF or to an anti NGF antibody;

• Use of biologics other than study medication, Live or live-attenuated intranasal vaccines (eg, Flumist), are allowable exceptions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mobile Diagnostic Center	Mobile	Alabama	United States	36608
2	Seton Medical Management, Inc.	Mobile	Alabama	United States	36608
3	Phoenix Rheumatology Specialists, Ltd.	Phoenix	Arizona	United States	85006
4	Radiant Research, Inc	Scottsdale	Arizona	United States	85251
5	Advanced Arthritis Care and Research	Scottsdale	Arizona	United States	85258
6	Catalina Pointe Clinical Research, Inc	Tucson	Arizona	United States	85704
7	Ft. Smith Rheumatology, PC	Fort Smith	Arkansas	United States	72903
8	Larry Watkins, MD	Little Rock	Arkansas	United States	72205
9	Lynn Institute of the Ozarks	Little Rock	Arkansas	United States	72205
10	OrthoArkansas, PA	Little Rock	Arkansas	United States	72205
11	Radiology Consultants	Little Rock	Arkansas	United States	72205
12	Medvin Clinical Research	Covina	California	United States	91723
13	Pacific Arthritis Care Center	Los Angeles	California	United States	90045
14	Staywell Research	Northridge	California	United States	91325
15	University Imaging Centers	Northridge	California	United States	91325
16	C Michael Neuwelt, MD	San Leandro	California	United States	94578
17	Pacific Arthritis Center Medical Group	Santa Maria	California	United States	93454
18	Medvin Clinical Research	Whittier	California	United States	90606
19	RASF Clinical Research Center	Boca Raton	Florida	United States	33486
20	Sunrise Medical Research	Lauderdale Lake	Florida	United States	33319
21	Melbourne Internal Medicine Associates	Melbourne	Florida	United States	32901
22	MIMA Century Research Associate	Melbourne	Florida	United States	32901
23	Osler Medical, Inc.	Melbourne	Florida	United States	32901
24	Renstar Medical Research	Ocala	Florida	United States	344471
25	American Family Medical	Ocala	Florida	United States	34471
26	Renstar Medical Research	Ocala	Florida	United States	34471
27	Paddock Park Clinical Research	Ocala	Florida	United States	34474
28	Medical Research Group of Central Florida	Orange City	Florida	United States	32763
29	Pensacola Research Consultants, Inc.	Pensacola	Florida	United States	32504
30	Radiant Research, Inc	Pinellas Park	Florida	United States	33781
31	Jarred Frydman, DO	Plantation	Florida	United States	33324
32	Orthopaedic Center of South Flordia	Plantation	Florida	United States	33324
33	Advanced Medical Research	Port Orange	Florida	United States	32127
34	Center for Arthritis and Rheumatic Diseases	South Miami	Florida	United States	33143
35	Tampa Medical Group, P.A.	Tampa	Florida	United States	33614
36	Arthritis Center of North Georgia	Gainesville	Georgia	United States	30501
37	Radiant Research, Inc	Chicago	Illinois	United States	60654
38	Methodist Medical Group Rheumatology	Peoria	Illinois	United States	61602
39	Methodist Research Administration Office	Peoria	Illinois	United States	61602
40	Rockford Health Physicians	Rockford	Illinois	United States	61103-3692
41	Radiant Research, Inc	Overland Park	Kansas	United States	66202
42	Graves Gilbert Clinic	Bowling Green	Kentucky	United States	42101
43	Kentucky Medical Research Center	Lexington	Kentucky	United States	40504
44	Central Kentucky Research Associates	Mount Sterling	Kentucky	United States	40353
45	Mt. Sterling Clinic	Mount Sterling	Kentucky	United States	40353
46	Boston Clinical Trails, Inc.	Boston	Massachusetts	United States	02135
47	Woodrail Clinic	Columbia	Missouri	United States	65203
48	University Physicians	Columbia	Missouri	United States	65212
49	Kansas City Internal Medicine	Lee's Summit	Missouri	United States	64086
50	Clayton Medical Research	Saint Louis	Missouri	United States	63117
51	Advance Clinical Research Inc	Saint Louis	Missouri	United States	63128
52	St. Louis Center for Clinical Research	Saint Louis	Missouri	United States	63128
53	Barbara A. Caciolo	Saint Louis	Missouri	United States	63139
54	Montana Medical Research, Inc	Missoula	Montana	United States	59808
55	Internal Medical Associates of Grand Island, PC	Grand Island	Nebraska	United States	68803
56	Radiant Research, Inc	Las Vegas	Nevada	United States	89146
57	Buffalo Rheumatology	Orchard Park	New York	United States	14127
58	Upstate Clinical Research Associates	Williamsville	New York	United States	14221
59	Arthritis and Osteoporosis Consultants of the Carolinas	Charlotte	North Carolina	United States	28207
60	Robert A. Harrell, MD	Durham	North Carolina	United States	27704
61	Piedmont Imaging	Winston-Salem	North Carolina	United States	27103
62	The Center for Clinical Research	Winston-Salem	North Carolina	United States	27103
63	Radiant Research, Inc	Columbus	Ohio	United States	43212
64	Clinical Research Source, Inc.	Perrysburg	Ohio	United States	43551
65	Bone Joint & Spine Surgeons, Inc.	Toledo	Ohio	United States	43623
66	McBride Clinic	Oklahoma City	Oklahoma	United States	73103
67	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
68	Healthcare Research Consultants	Tulsa	Oklahoma	United States	74135
69	Integrated Medical Group PC/Fleetwood Clinical Research	Fleetwood	Pennsylvania	United States	19522
70	Research Across America @ Oyster Point Family Health Center	Lancaster	Pennsylvania	United States	17601
71	Arthritis Group	Philadelphia	Pennsylvania	United States	19152
72	Allegheny North Arthritis Center	Wexford	Pennsylvania	United States	15090
73	Jeffry A. Lindenbaum D.O., P.C.	Yardley	Pennsylvania	United States	19067
74	Anderson Radiology	Anderson	South Carolina	United States	29621
75	Primary Care Associates	Anderson	South Carolina	United States	29621
76	Radiant Research, Inc.	Anderson	South Carolina	United States	29621
77	Carolina Health Specialists	Myrtle Beach	South Carolina	United States	29572
78	Sarah Cannon Research Institute, LLC	Germantown	Tennessee	United States	38138
79	Wolf River Medical Group. LLC	Germantown	Tennessee	United States	38138
80	The Jackson Clinic, PA	Jackson	Tennessee	United States	38305
81	Office of John M. Joseph, M.D.	Carrollton	Texas	United States	75007
82	Arthritis Care and Diagnostic Center	Dallas	Texas	United States	75231
83	Houston Medical Research Associates	Houston	Texas	United States	77090
84	Nothwest Diagonstic Clinic, PA	Houston	Texas	United States	77090
85	Arthritis & Osteoporosis Center of South Texas	San Antonio	Texas	United States	78232
86	Texas Research Center, LP	Sugar Land	Texas	United States	77479
87	Trinity Clinic, Office of Research Administration	Tyler	Texas	United States	75701
88	Trinity Clinic, Rheumatology	Tyler	Texas	United States	75701
89	Physicians' Research Options, LLC	Draper	Utah	United States	84020
90	Lone Peak Family Medicine	Draper	Utah	United States	84070
91	Granger Medical Clinic	West Valley City	Utah	United States	84120
92	Arthritis and Rheumatic Disease Associates, PC	Burke	Virginia	United States	22015
93	Alan E. Schulman, MD	Richmond	Virginia	United States	23226
94	Steven Maestrello, M.D.	Richmond	Virginia	United States	23294
95	Richard Neiman, MD Inc.	Kirkland	Washington	United States	98034
96	South Puget Sound Clinical Research Center	Olympia	Washington	United States	98502
97	Rainier Clinical Research Center, Inc.	Renton	Washington	United States	98057
98	Rheumatology and Pulmonary Clinic	Beckley	West Virginia	United States	25801
99	Aurora Advanced Healthcare	Milwaukee	Wisconsin	United States	53209
100	Arthritis Clinic	Racine	Wisconsin	United States	53406

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00994890
• Other Study ID Numbers: A4091043; SC OA SAFETY STUDY
• First Posted: Oct 14, 2009
• Last Update Posted: May 13, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: Double-blind safety
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip; Tanezumab

Study Results

Participant Flow

Pre-assignment Detail	Due to United States Food and Drug Administration (FDA) imposed clinical hold, study was terminated prematurely and a maximum of only 4 doses of the 7 planned doses of tanezumab (RN624 or PF-04383119) subcutaneous injection were administered in the study.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Period Title: Overall Study
STARTED	231	222	226
Treated	230	222	226
COMPLETED	0	0	0
NOT COMPLETED	231	222	226

Baseline Characteristics

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg	Total
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.	Total of all reporting groups
Overall Participants	230	222	226	678
Age, Customized (Count of Participants)
18 to 44 years	11 4.8%	7 3.2%	4 1.8%	22 3.2%
45 to 64 years	128 55.7%	124 55.9%	113 50%	365 53.8%
Greater than or equal to (>=) 65 years	91 39.6%	91 41%	109 48.2%	291 42.9%
Sex: Female, Male (Count of Participants)
Female	152 66.1%	157 70.7%	161 71.2%	470 69.3%
Male	78 33.9%	65 29.3%	65 28.8%	208 30.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	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. Treatment-emergent are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	Baseline up to 112 days after last dose of study medication (up to 345 days)

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
AEs	158 68.7%	169 76.1%	181 80.1%
SAEs	17 7.4%	12 5.4%	20 8.8%

2. Primary Outcome

Title	Number of Participants With Laboratory Abnormalities
Description	Laboratory analysis included blood chemistry, hematology, urinalysis and pregnancy test.
Time Frame	Baseline to Week 50

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	221	220	220
Count of Participants [Participants]	136 59.1%	121 54.5%	130 57.5%

3. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	All standard intervals (PR, QRS, QT, QT interval corrected for heart rate using Fridericia's formula [QTcF], QT interval corrected for heart rate using Bazett's formula [QTcB], RR intervals and heart rate) were analyzed. Participants with abnormal ECG findings reported as adverse events were presented.
Time Frame	Baseline up to Week 50

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
Atrioventricular block first degree	0 0%	1 0.5%	0 0%
Bundle branch block right	0 0%	0 0%	1 0.4%
Supraventricular extrasystoles	0 0%	0 0%	1 0.4%
Supraventricular tachycardia	0 0%	1 0.5%	0 0%
Tachycardia	1 0.4%	1 0.5%	2 0.9%
ECG QRS complex prolonged	1 0.4%	0 0%	0 0%
ECG T wave abnormal	0 0%	1 0.5%	0 0%
ECG T wave inversion	1 0.4%	0 0%	1 0.4%

4. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 2
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. 'Number Analyzed' signifies those participants who were evaluable for this measure at given time points for each group, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	229	222	225
Baseline	2.04 (3.93)	1.52 (3.17)	1.76 (3.53)
Change at Week 2	-0.43 (1.51)	-0.36 (2.04)	-0.23 (1.78)

5. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 4
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	218	215	218
Mean (Standard Deviation) [units on a scale]	-0.35 (1.72)	-0.15 (2.12)	-0.10 (1.83)

6. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 8
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	215	216	216
Mean (Standard Deviation) [units on a scale]	-0.39 (2.10)	-0.08 (2.30)	-0.34 (2.14)

7. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 16
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	188	207	203
Mean (Standard Deviation) [units on a scale]	-0.60 (2.24)	-0.17 (2.66)	-0.24 (2.61)

8. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 24
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	161	176	165
Mean (Standard Deviation) [units on a scale]	-0.46 (2.14)	-0.38 (2.53)	-0.19 (2.44)

9. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 32
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	81	90	91
Mean (Standard Deviation) [units on a scale]	-0.72 (2.15)	-0.11 (2.26)	-0.34 (3.02)

10. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 40
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	22	23	27
Mean (Standard Deviation) [units on a scale]	-0.82 (2.11)	-0.39 (1.41)	0.00 (3.98)

11. Primary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Week 48
Description	NIS: 74-item, assess cranial nerves, muscle weakness, reflexes, sensation; scored separately for left, right limbs (37 items for each). Cranial nerves included 5 items (3rd nerve, 6th nerve, facial weakness, palate weakness, tongue weakness), muscle weakness included 19 items (respiratory,neck flexion, shoulder abduction, elbow flexion, brachioradialis,elbow extension, wrist flexion,wrist extension,finger flexion,finger spread,thumb abduction,hip flexion,hip extension,knee flexion,knee extension,ankle dorsiflexors,ankle plantar flexors,toe extensors,toe flexors), each item scored on scale 0=normal to 4=paralysis, higher score=greater weakness. Reflexes included 5 items (quadriceps femoris, triceps surae, biceps brachii, triceps brachii, brachioradialis), sensation included 4 items each for great toe and index finger (touch pressure, pin prick, vibration, joint position), each item scored as 0=normal, 1=decreased, 2=absent. Total NIS score range 0-244, higher score=greater impairment.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Results are not reported for Tanezumab 5 mg group because all participants in this group had discontinued the study before Week 48.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	1	0	1
Mean (Standard Deviation) [units on a scale]	-2.00 (NA)	0.00 (NA)

12. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Physical Findings
Description	Physical examination included examination of abdomen, ears, extremities, eyes, head, heart, lungs, lymph nodes, neck, nose, skin, throat, thyroid, muscoskeletal, neurological and peripheral vascular system.
Time Frame	Baseline to Week 50

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
Count of Participants [Participants]	13 5.7%	13 5.9%	18 8%

13. Primary Outcome

Title	Number of Participants With Anti-Drug Antibody (ADA) at Day 1
Description	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).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure at any time point.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	215	213	208
Count of Participants [Participants]	1 0.4%	1 0.5%	1 0.4%

14. Primary Outcome

Title	Number of Participants With Anti-Drug Antibody (ADA) at Week 8
Description	Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative ELISA.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure at any time point.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	206	204	203
Count of Participants [Participants]	1 0.4%	2 0.9%	1 0.4%

15. Primary Outcome

Title	Number of Participants With Anti-Drug Antibody (ADA) at Week 24
Description	Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative ELISA.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure at any time point.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	78	93	82
Count of Participants [Participants]	0 0%	1 0.5%	0 0%

16. Primary Outcome

Title	Number of Participants With Anti-Drug Antibody (ADA) at Week 50
Description	Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative ELISA.
Time Frame	Week 50

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure at any time point.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	171	176	172
Count of Participants [Participants]	3 1.3%	3 1.4%	1 0.4%

17. Primary Outcome

Title	Number of Participants With Vital Sign Abnormalities
Description	Examination of vital signs included body temperature, systolic blood pressure, diastolic blood pressure, pulse rate and respiratory rate. Participants with abnormal vital sign findings reported as adverse events were presented.
Time Frame	Baseline up to Week 50

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
Blood pressure increased	0 0%	3 1.4%	1 0.4%
Hypertension	8 3.5%	4 1.8%	5 2.2%
Hypotension	0 0%	0 0%	1 0.4%

18. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Day 1
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
Count of Participants [Participants]	9 3.9%	12 5.4%	9 4%

19. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Week 2
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	221	218	219
Count of Participants [Participants]	7 3%	3 1.4%	4 1.8%

20. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Week 4
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	219	212	218
Count of Participants [Participants]	1 0.4%	1 0.5%	1 0.4%

21. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Week 8
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	186	191	192
Count of Participants [Participants]	4 1.7%	6 2.7%	7 3.1%

22. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Week 16
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	107	123	113
Count of Participants [Participants]	2 0.9%	1 0.5%	1 0.4%

23. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Week 24
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	54	67	64
Count of Participants [Participants]	1 0.4%	0 0%	0 0%

24. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Week 32
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Week 32

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	31	28	32
Count of Participants [Participants]	0 0%	0 0%	0 0%

25. Primary Outcome

Title	Number of Participants With Injection-Site Reactions at Week 40
Description	Assessment of the injection-site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time Frame	Week 40

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	11	11	12
Count of Participants [Participants]	0 0%	0 0%	0 0%

26. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or index hip during past 48 hours. It was calculated as 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.
Time Frame	Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	220	222
Baseline	6.35 (1.48)	6.48 (1.56)	6.30 (1.48)
Change at Week 2	-2.01 (2.02)	-1.97 (2.18)	-1.61 (2.00)
Change at Week 4	-2.43 (2.11)	-2.68 (2.15)	-2.50 (2.02)
Change at Week 8	-2.20 (2.14)	-2.76 (2.25)	-2.71 (2.14)
Change at Week 16	-2.18 (2.25)	-2.85 (2.32)	-2.71 (2.15)
Change at Week 24	-2.16 (2.29)	-2.84 (2.31)	-2.69 (2.17)
Change at Week 32	-2.15 (2.26)	-2.82 (2.32)	-2.66 (2.14)

27. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint and index hip during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on NRS of 0 to 10, with higher scores indicated worse function. Total score range for WOMAC physical function subscale score was 0 to 10, where higher scores indicated worse function.
Time Frame	Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	220	223
Baseline	6.49 (1.54)	6.58 (1.55)	6.47 (1.53)
Change at Week 2	-2.10 (2.01)	-2.13 (2.15)	-1.92 (1.96)
Change at Week 4	-2.50 (2.16)	-2.70 (2.22)	-2.64 (2.09)
Change at Week 8	-2.29 (2.10)	-2.83 (2.26)	-2.80 (2.23)
Change at Week 16	-2.28 (2.20)	-2.89 (2.35)	-2.84 (2.22)
Change at Week 24	-2.26 (2.23)	-2.89 (2.37)	-2.84 (2.21)
Change at Week 32	-2.23 (2.22)	-2.90 (2.36)	-2.79 (2.20)

28. Secondary Outcome

Title	Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 2, 4, 8,16, 24, 32, 40, 48 and 56
Description	Participants answered: "Considering all the ways your osteoarthritis in your knee (or hip) affects you, how are you doing today?" Participants responded by using a 5-point scale where 1 = very good (no symptom and limitation of normal activities) and 5 = very poor (very severe symptoms and inability to carry out normal activities).
Time Frame	Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	228	222	225
Baseline	3.38 (0.59)	3.36 (0.57)	3.32 (0.53)
Change at Week 2	-0.70 (0.78)	-0.64 (0.85)	-0.64 (0.84)
Change at Week 4	-0.85 (0.79)	-0.86 (0.86)	-0.77 (0.87)
Change at Week 8	-0.72 (0.80)	-0.83 (0.83)	-0.82 (0.92)
Change at Week 16	-0.69 (0.83)	-0.84 (0.86)	-0.80 (0.91)
Change at Week 24	-0.71 (0.87)	-0.82 (0.88)	-0.80 (0.88)
Change at Week 32	-0.69 (0.88)	-0.82 (0.88)	-0.80 (0.88)

29. Secondary Outcome

Title	Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response
Description	OMERACT-OARSI response: greater than or equal to (>=) 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	Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	220	223
Week 2	57.8 25.1%	58.6 26.4%	49.3 21.8%
Week 4	64.9 28.2%	70.5 31.8%	73.5 32.5%
Week 8	61.8 26.9%	68.6 30.9%	70.9 31.4%
Week 16	59.1 25.7%	68.6 30.9%	72.2 31.9%
Week 24	58.7 25.5%	68.2 30.7%	71.7 31.7%
Week 32	58.2 25.3%	68.2 30.7%	71.7 31.7%

30. Secondary Outcome

Title	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
Description	Percentage of participants with at least 30%, 50%, 70% and 90% reduction from baseline in WOMAC pain subscale score are reported. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or index hip during past 48 hours. It was calculated as mean of the scores from the 5 individual questions scored on a 0 to 10 NRS, where higher scores indicated higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicated higher pain.
Time Frame	Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	220	222
Week 2: at least 30% reduction	48.9 21.3%	49.1 22.1%	41.4 18.3%
Week 2: at least 50% reduction	28.4 12.3%	31.4 14.1%	23.9 10.6%
Week 2: at least 70% reduction	13.8 6%	16.8 7.6%	14.0 6.2%
Week 2: at least 90% reduction	4.9 2.1%	3.6 1.6%	3.6 1.6%
Week 4: at least 30% reduction	57.3 24.9%	62.7 28.2%	60.4 26.7%
Week 4: at least 50% reduction	39.1 17%	40.9 18.4%	41.0 18.1%
Week 4: at least 70% reduction	21.3 9.3%	24.5 11%	22.5 10%
Week 4: at least 90% reduction	7.6 3.3%	6.8 3.1%	6.3 2.8%
Week 8: at least 30% reduction	50.7 22%	62.7 28.2%	66.2 29.3%
Week 8: at least 50% reduction	35.1 15.3%	46.4 20.9%	46.4 20.5%
Week 8: at least 70% reduction	18.2 7.9%	26.8 12.1%	27.0 11.9%
Week 8: at least 90% reduction	7.6 3.3%	11.4 5.1%	10.8 4.8%
Week 16: at least 30% reduction	52.4 22.8%	62.3 28.1%	65.3 28.9%
Week 16: at least 50% reduction	37.3 16.2%	50.0 22.5%	45.5 20.1%
Week 16: at least 70% reduction	20.4 8.9%	28.6 12.9%	28.4 12.6%
Week 16: at least 90% reduction	6.2 2.7%	11.8 5.3%	12.2 5.4%
Week 24: at least 30% reduction	50.2 21.8%	62.7 28.2%	65.3 28.9%
Week 24: at least 50% reduction	37.3 16.2%	50.0 22.5%	45.5 20.1%
Week 24: at least 70% reduction	20.4 8.9%	28.2 12.7%	28.8 12.7%
Week 24: at least 90% reduction	7.1 3.1%	11.8 5.3%	11.7 5.2%
Week 32: at least 30% reduction	51.1 22.2%	62.3 28.1%	64.9 28.7%
Week 32: at least 50% reduction	36.9 16%	49.5 22.3%	44.1 19.5%
Week 32: at least 70% reduction	20.4 8.9%	27.7 12.5%	27.9 12.3%
Week 32: at least 90% reduction	6.7 2.9%	11.4 5.1%	11.3 5%

31. Secondary Outcome

Title	Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
Description	WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or index hip during past 48 hours. It is calculated as 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. Participants with specified reduction (as percent) from baseline at Week 16 are reported.
Time Frame	Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	115	135	118
Week 16: greater than (>) 0%	82.6 35.9%	85.2 38.4%	89.0 39.4%
Week 16: >=10%	74.8 32.5%	81.5 36.7%	82.2 36.4%
Week 16: >=20%	65.2 28.3%	71.9 32.4%	73.7 32.6%
Week 16: >=30%	58.3 25.3%	63.0 28.4%	67.8 30%
Week 16: >=40%	47.0 20.4%	57.0 25.7%	60.2 26.6%
Week 16: >=50%	43.5 18.9%	51.9 23.4%	50.0 22.1%
Week 16: >=60%	33.0 14.3%	41.5 18.7%	41.5 18.4%
Week 16: >=70%	28.7 12.5%	32.6 14.7%	33.9 15%
Week 16: >=80%	18.3 8%	21.5 9.7%	22.9 10.1%
Week 16: >=90%	9.6 4.2%	14.8 6.7%	14.4 6.4%
Week 16: 100%	4.3 1.9%	3.7 1.7%	5.9 2.6%

32. Secondary Outcome

Title	Percentage of Participants With Improvement of At Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis
Description	Participants answered: "Considering all the ways your osteoarthritis in your knee (or hip) affects you, how are you doing today?" Participants responded by using a 5-point scale where 1 = very good and 5 = very poor. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value.
Time Frame	Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	228	222	225
Week 2	14.5 6.3%	15.8 7.1%	13.3 5.9%
Week 4	20.2 8.8%	20.3 9.1%	16.9 7.5%
Week 8	15.8 6.9%	18.9 8.5%	24.9 11%
Week 16	15.4 6.7%	18.0 8.1%	20.9 9.2%
Week 24	16.7 7.3%	18.5 8.3%	20.0 8.8%
Week 32	16.2 7%	18.5 8.3%	20.0 8.8%

33. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in index knee or index hip during past 48 hours. It is calculated as mean of the scores from 2 individual questions scored on NRS of 0 to 10, with higher scores indicate higher stiffness. Total score range for WOMAC stiffness subscale score is 0 to 10, where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in movement of knee or hip.
Time Frame	Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	220	223
Baseline	6.78	6.85	6.73
Change at Week 2	-2.32	-2.42	-2.29
Change at Week 4	-2.73	-3.01	-2.99
Change at Week 8	-2.43	-3.17	-3.05
Change at Week 16	-2.43	-3.20	-3.15
Change at Week 24	-2.41	-3.20	-3.10
Change at Week 32	-2.36	-3.21	-3.05

34. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	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. Each item was scored on a 0 to 10 NRS scale, where higher scores indicated higher pain/stiffness or worse function. WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranged from 0 to 10, where higher score indicated worse response.
Time Frame	Baseline, Week 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	220	223
Baseline	6.54 (1.45)	6.64 (1.50)	6.50 (1.41)
Change at Week 2	-2.14 (1.99)	-2.18 (2.13)	-1.94 (1.96)
Change at Week 4	-2.56 (2.14)	-2.80 (2.18)	-2.71 (2.05)
Change at Week 8	-2.31 (2.11)	-2.92 (2.24)	-2.85 (2.23)
Change at Week 16	-2.30 (2.21)	-2.98 (2.29)	-2.90 (2.22)
Change at Week 24	-2.27 (2.26)	-2.97 (2.32)	-2.88 (2.21)
Change at Week 32	-2.25 (2.23)	-2.98 (2.31)	-2.83 (2.20)

35. Secondary Outcome

Title	Change From Baseline in WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	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.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	220	222
Baseline	6.15 (1.86)	6.32 (1.84)	6.20 (1.86)
Change at Week 2	-1.95 (2.17)	-1.94 (2.38)	-1.67 (2.34)
Change at Week 4	-2.26 (2.31)	-2.59 (2.34)	-2.45 (2.29)
Change at Week 8	-2.03 (2.42)	-2.65 (2.50)	-2.63 (2.32)
Change at Week 16	-2.00 (2.54)	-2.66 (2.48)	-2.57 (2.46)
Change at Week 24	-1.96 (2.55)	-2.65 (2.51)	-2.60 (2.42)
Change at Week 32	-1.96 (2.51)	-2.63 (2.51)	-2.56 (2.43)

36. Secondary Outcome

Title	Change From Baseline in WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs at Week 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	Participants answered: "How much pain have you had when going up or down the stairs?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. Missing data was imputed using last observation carried forward (LOCF) method. Due to implementation of the FDA clinical hold, all ongoing participants were discontinued from treatment and did not have an opportunity to complete the 56-week treatment period and no efficacy data beyond the Week 32 visit (i.e., Weeks 40, 48 and 56) was collected.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	224	219	222
Baseline	7.52 (1.64)	7.64 (1.68)	7.54 (1.72)
Change at Week 2	-2.34 (2.28)	-2.25 (2.43)	-1.99 (2.30)
Change at Week 4	-2.86 (2.58)	-3.01 (2.47)	-2.77 (2.45)
Change at Week 8	-2.60 (2.48)	-3.03 (2.59)	-3.01 (2.53)
Change at Week 16	-2.51 (2.63)	-3.05 (2.67)	-3.01 (2.62)
Change at Week 24	-2.47 (2.66)	-3.00 (2.67)	-2.98 (2.55)
Change at Week 32	-2.46 (2.63)	-3.01 (2.66)	-2.94 (2.54)

37. Secondary Outcome

Title	Time to Discontinuation Due to Lack of Efficacy
Description	Median time to discontinuation due to lack of efficacy was estimated using Kaplan-Meier method.
Time Frame	Baseline up to Week 50

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
Median (Full Range) [days]	NA	NA	NA

38. Secondary Outcome

Title	Number of Participants Who Discontinued Due to Lack of Efficacy
Time Frame	Baseline up to Week 50

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
Count of Participants [Participants]	0 0%	0 0%	1 0.4%

39. Secondary Outcome

Title	Percentage of Participants Who Used Concomitant Analgesic Medication
Description	United States Food and Drug Administration (FDA) approved analgesics 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 and viscosupplementation (example, hyaluronan) and were prescribed at the discretion of the Investigator.
Time Frame	Week 2, 4, 8, 16, 24, 32, 40, 48, 56, 64

Outcome Measure Data

Analysis Population Description

ITT analysis set. 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. 'Number Analyzed' signifies those participants who were evaluable for this measure at given time points for each group. Data were not collected beyond Week 48 due to premature termination of the study in response to FDA clinical hold.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	219	221
Week 2	53.8 23.4%	49.8 22.4%	52.5 23.2%
Week 4	52.9 23%	47.7 21.5%	51.6 22.8%
Week 8	53.7 23.3%	47.9 21.6%	51.6 22.8%
Week 16	50.6 22%	47.8 21.5%	50.5 22.3%
Week 24	49.5 21.5%	49.0 22.1%	48.9 21.6%
Week 32	33.3 14.5%	47.6 21.4%	52.2 23.1%
Week 40	100 43.5%	0 0%	100 44.2%
Week 48	0 0%

40. Secondary Outcome

Title	Days Per Week of Concomitant Analgesic Medication Usage
Description	United States FDA-approved analgesics were permitted as concomitant medications to relieve the pain of OA. These medications included opioids, topical analgesics, NSAIDs, capsaicin products and viscosupplementation (example, hyaluronan) and were prescribed at the discretion of the Investigator.
Time Frame	Week 2, 4, 8, 16, 24, 32, 40, 48, 56, 64

Outcome Measure Data

Analysis Population Description

ITT analysis set. Here, 'Overall number of participants analyzed' signifies those participants who were evaluable for this measure. 'number analyzed' signifies those participants who were evaluable for this measure at given time points for each group. Data were not collected beyond Week 48 due to premature termination of the study in response to FDA clinical hold.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	225	219	221
Week 2	7.0	0.0	7.0
Week 4	7.0	0.0	7.0
Week 8	7.0	0.0	2.9
Week 16	2.5	0.0	0.4
Week 24	0.0	0.0	0.0
Week 32	0.0	0.0	7.0
Week 40	7.0	0.0	7.0
Week 48	0.0

41. Other Pre-specified Outcome

Title	Number of Participants With Subcutaneous Doses of Study Medication
Description	Number of participants are reported based on the maximum number of subcutaneous doses of study medication received.
Time Frame	Day 1 up to Week 24

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.	Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
Measure Participants	230	222	226
1 dose	48 20.9%	36 16.2%	38 16.8%
2 doses	99 43%	89 40.1%	103 45.6%
3 doses	64 27.8%	72 32.4%	61 27%
4 doses	19 8.3%	25 11.3%	24 10.6%

Adverse Events

Adverse Event Reporting Description	Cases of osteonecrosis (ON) reported in this and other A409 studies conducted up to 2010 were adjudicated post-hoc by an expert committee(2010-2012). Few of these events (2 of 87 reported ON cases), were confirmed as ON by the committee. Source: https://doi.org/10.1002/art.39492
Arm/Group Title	Tanezumab 2.5 mg		Tanezumab 5 mg		Tanezumab 10 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection subcutaneously every 8 weeks up to 24 weeks.		Tanezumab (RN624 or PF-04383119) 5 mg injection subcutaneously every 8 weeks up to 24 weeks.		Tanezumab (RN624 or PF-04383119) 10 mg injection subcutaneously every 8 weeks up to 24 weeks.
All Cause Mortality
	Tanezumab 2.5 mg		Tanezumab 5 mg		Tanezumab 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tanezumab 2.5 mg		Tanezumab 5 mg		Tanezumab 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/230 (7.4%)		12/222 (5.4%)		20/226 (8.8%)
Cardiac disorders
Acute myocardial infarction	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Myocardial infarction	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Gastrooesophageal reflux disease	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Haemorrhoids	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Oesophageal spasm	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Small intestinal obstruction	0/230 (0%)		1/222 (0.5%)		1/226 (0.4%)
Vomiting	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
General disorders
Chest pain	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Non-cardiac chest pain	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Hepatobiliary disorders
Sphincter of Oddi dysfunction	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Infections and infestations
Cellulitis	1/230 (0.4%)		1/222 (0.5%)		1/226 (0.4%)
Lobar pneumonia	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Pneumonia	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Injury, poisoning and procedural complications
Foot fracture	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Hip fracture	1/230 (0.4%)		0/222 (0%)		1/226 (0.4%)
Joint dislocation	0/230 (0%)		1/222 (0.5%)		0/226 (0%)
Tibia fracture	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/230 (1.7%)		1/222 (0.5%)		3/226 (1.3%)
Arthritis	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Back pain	1/230 (0.4%)		1/222 (0.5%)		0/226 (0%)
Bunion	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Foot deformity	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Fracture malunion	0/230 (0%)		1/222 (0.5%)		0/226 (0%)
Intervertebral disc protrusion	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Neck pain	0/230 (0%)		1/222 (0.5%)		0/226 (0%)
Osteoarthritis	2/230 (0.9%)		1/222 (0.5%)		4/226 (1.8%)
Osteonecrosis	1/230 (0.4%)		4/222 (1.8%)		4/226 (1.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/230 (0.4%)		0/222 (0%)		1/226 (0.4%)
Malignant melanoma	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Nervous system disorders
Headache	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Renal and urinary disorders
Nephrolithiasis	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Lung disorder	1/230 (0.4%)		0/222 (0%)		0/226 (0%)
Pneumonia aspiration	0/230 (0%)		0/222 (0%)		1/226 (0.4%)
Skin and subcutaneous tissue disorders
Acute generalised exanthematous pustulosis	0/230 (0%)		1/222 (0.5%)		0/226 (0%)
Other (Not Including Serious) Adverse Events
	Tanezumab 2.5 mg		Tanezumab 5 mg		Tanezumab 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	132/230 (57.4%)		137/222 (61.7%)		153/226 (67.7%)
Gastrointestinal disorders
Diarrhoea	2/230 (0.9%)		3/222 (1.4%)		6/226 (2.7%)
Nausea	6/230 (2.6%)		6/222 (2.7%)		11/226 (4.9%)
General disorders
Fatigue	3/230 (1.3%)		0/222 (0%)		8/226 (3.5%)
Injection site reaction	19/230 (8.3%)		21/222 (9.5%)		20/226 (8.8%)
Oedema peripheral	9/230 (3.9%)		16/222 (7.2%)		22/226 (9.7%)
Infections and infestations
Bronchitis	6/230 (2.6%)		9/222 (4.1%)		7/226 (3.1%)
Nasopharyngitis	3/230 (1.3%)		5/222 (2.3%)		6/226 (2.7%)
Sinusitis	6/230 (2.6%)		9/222 (4.1%)		6/226 (2.7%)
Upper respiratory tract infection	12/230 (5.2%)		9/222 (4.1%)		12/226 (5.3%)
Urinary tract infection	11/230 (4.8%)		12/222 (5.4%)		20/226 (8.8%)
Injury, poisoning and procedural complications
Contusion	4/230 (1.7%)		1/222 (0.5%)		5/226 (2.2%)
Fall	7/230 (3%)		5/222 (2.3%)		12/226 (5.3%)
Joint injury	3/230 (1.3%)		6/222 (2.7%)		6/226 (2.7%)
Investigations
Blood alkaline phosphatase increased	3/230 (1.3%)		3/222 (1.4%)		5/226 (2.2%)
Blood creatine phosphokinase increased	6/230 (2.6%)		8/222 (3.6%)		9/226 (4%)
Blood lactate dehydrogenase increased	1/230 (0.4%)		5/222 (2.3%)		3/226 (1.3%)
Blood triglycerides increased	1/230 (0.4%)		5/222 (2.3%)		2/226 (0.9%)
Metabolism and nutrition disorders
Vitamin D deficiency	2/230 (0.9%)		2/222 (0.9%)		5/226 (2.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	35/230 (15.2%)		30/222 (13.5%)		26/226 (11.5%)
Back pain	7/230 (3%)		8/222 (3.6%)		8/226 (3.5%)
Bursitis	6/230 (2.6%)		3/222 (1.4%)		1/226 (0.4%)
Joint swelling	8/230 (3.5%)		10/222 (4.5%)		13/226 (5.8%)
Muscle spasms	5/230 (2.2%)		6/222 (2.7%)		10/226 (4.4%)
Musculoskeletal pain	8/230 (3.5%)		15/222 (6.8%)		12/226 (5.3%)
Osteoarthritis	6/230 (2.6%)		11/222 (5%)		16/226 (7.1%)
Pain in extremity	14/230 (6.1%)		12/222 (5.4%)		16/226 (7.1%)
Rotator cuff syndrome	4/230 (1.7%)		0/222 (0%)		5/226 (2.2%)
Synovial cyst	2/230 (0.9%)		1/222 (0.5%)		9/226 (4%)
Nervous system disorders
Burning sensation	1/230 (0.4%)		5/222 (2.3%)		2/226 (0.9%)
Carpal tunnel syndrome	8/230 (3.5%)		3/222 (1.4%)		7/226 (3.1%)
Dizziness	3/230 (1.3%)		5/222 (2.3%)		8/226 (3.5%)
Headache	9/230 (3.9%)		6/222 (2.7%)		10/226 (4.4%)
Hypoaesthesia	14/230 (6.1%)		6/222 (2.7%)		15/226 (6.6%)
Paraesthesia	13/230 (5.7%)		17/222 (7.7%)		25/226 (11.1%)
Psychiatric disorders
Anxiety	5/230 (2.2%)		2/222 (0.9%)		1/226 (0.4%)
Respiratory, thoracic and mediastinal disorders
Cough	5/230 (2.2%)		3/222 (1.4%)		5/226 (2.2%)
Skin and subcutaneous tissue disorders
Rash	4/230 (1.7%)		6/222 (2.7%)		1/226 (0.4%)
Vascular disorders
Hypertension	8/230 (3.5%)		4/222 (1.8%)		5/226 (2.2%)

Limitations/Caveats

Due to United States FDA imposed clinical hold, enrollment was stopped and study was terminated prematurely. Due to this, injection-site reaction data were not collected beyond Week 40 and NIS data were not collected beyond Week 48.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.