Long Term Safety and Efficacy Study of Tanezumab in Japanese Adult Subjects With Chronic Low Back Pain

NCT02725411 | Completed Phase 3 Results DMC

• 2 other identifiers: A4091063JAPAN CLBP SC STUDY
• Study Type: interventional
• Target: 277
• Locations: 1 country
• Sites: 55

Brief Summary

This study will investigate the long-term safety and efficacy of a fixed dose of tanezumab 5 mg and 10 mg administered subcutaneously (SC) seven times at 8 week intervals. The primary objective of this study is to evaluate the long term safety of tanezumab 5 mg and 10 mg administrated SC every 8 weeks (7 administrations). In addition, the study will evaluate the long term analgesic efficacy of tanezumab 5 mg and 10 mg SC administered every 8 weeks (7 administrations).

Conditions

Low Back Pain

Keywords

Chronic low back pain; Chronic pain

Outcome Measures

Primary Outcomes (29)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 24 weeks after last dose of study drug (up to Week 80) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.

  Baseline (Day 1) up to 24 weeks after last dose of study drug (up to Week 80)

• Number of Participants With Treatment-Emergent Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Treatment-related AE was any untoward medical occurrence attributed to study drug in participant who received study drug. 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 were events between first dose of study drug and up to 24 weeks after last dose of study drug (up to Week 80). Relatedness to study drug was assessed by the investigator. AEs included both serious and non-serious AEs.

  Baseline up to 24 weeks after last dose of study drug (up to Week 80)

• Number of Participants With Clinically Significant Laboratory Test Abnormalities

  Abnormality criteria included: hemoglobin (HGB); hematocrit; erythrocytes \< 0.8\*lower limit of normal (LLN); erythrocyte mean corpuscular volume/HGB/ HGB concentration, erythrocytes distribution width \<0.9\*LLN, \>1.1\*upper limit of normal (ULN); platelets \<0.5\*LLN,\>1.75\* ULN; white blood cell count\<0.6\*LLN, \>1.5\*ULN; lymphocytes, leukocytes, neutrophils \<0.8\*LLN, \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; total bilirubin\>1.5\*ULN; aspartate aminotransferase (AT), alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase \>3.0\*ULN; total protein; albumin\<0.8\*LLN, \>1.2\*ULN; blood urea nitrogen, creatinine, cholesterol, triglycerides \>1.3\*ULN; urate \>1.2\*ULN; sodium \<0.95\*LLN,\>1.05\*ULN; potassium, chloride, calcium, magnesium, bicarbonate \<0.9\*LLN, \>1.1\*ULN; phosphate \<0.8\*LLN, \>1.2\*ULN; glucose \<0.6\*LLN, \>1.5\*ULN; HGB A1C \>1.3\*ULN; creatine kinase \>2.0\*ULN; nitrite \>=1. Investigator judged clinical significance of laboratory test abnormalities.

  Baseline up to Week 80

• Number of Participants With Clinically Significant Vital Signs Abnormalities

  Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate. Investigator judged clinical significance of vital signs' abnormalities.

  Baseline up to Week 80

• Number of Participants With Confirmed Orthostatic Hypotension From Baseline up to Week 80

  Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: for systolic blood pressure (BP) less than or equal to (\<=) 150 millimeter of mercury (mmHg) (mean supine): reduction in systolic BP \>=20 mmHg or reduction in diastolic BP \>=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP greater than (\>) 150 mmHg (mean supine): reduction in systolic BP \>=30 mmHg or reduction in diastolic BP \>=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed.

  Baseline up to Week 80

• Change From Screening in Mean Total Symptom Impact Score as Per Survey of Autonomic Symptoms (SAS) at Week 24

  SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

  Screening (up to 37 days before Day 1), Week 24

• Change From Screening in Mean Total Symptom Impact Score as Per Survey of Autonomic Symptoms (SAS) at Week 56

  SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

  Screening, Week 56

• Change From Screening in Mean Total Symptom Impact Scores as Per Survey of Autonomic Symptoms (SAS) at Week 80

  SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

  Screening, Week 80

• Change From Screening in Mean Total Symptom Impact Score as Per Survey of Autonomic Symptoms (SAS) at Early Termination Follow-up Visit 1

  SAS: participant rated 12 items questionnaire for males; 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants answered "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If participant answered "Yes" for a symptom, then impact of that symptom was rated on 5 point scale (1 \[least sever impact\] to 5 \[most severe impact\]); higher scores = more severe impact of symptoms. Total impact score = sum of impact of all symptoms; range for males =0 (no impact) to 60 (extreme impact); females =0 (no impact) to 55 (extreme impact); higher scores = more severe impact of symptoms on participants' well-being. Participants discontinuing from study treatment before Week 56, had early termination follow-up visit 1 at 8 weeks after last dose of tanezumab or placebo matched to tanezumab.

  Screening, Early Termination Follow-up Visit 1 (at 8 weeks after last dose of tanezumab or placebo matched to tanezumab)

• Change From Screening in Mean Total Symptom Impact Scores as Per Survey of Autonomic Symptoms (SAS) at Early Termination Follow-up Visit 3

  SAS: participant rated 12 items questionnaire for males; 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants answered "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If participant answered "Yes" for a symptom, then impact of that symptom was rated on 5 point scale (1 \[least sever impact\] to 5 \[most severe impact\]); higher scores = more severe impact of symptoms. Total impact score = sum of impact of all symptoms; range for males =0 (no impact) to 60 (extreme impact); females =0 (no impact) to 55 (extreme impact); higher scores = more severe impact of symptoms on participants' well-being. Participants discontinuing from study treatment before Week 56, had early termination follow-up visit 3 at 24 weeks after last dose of tanezumab or placebo matched to tanezumab.

  Screening, Early Termination Follow-up Visit 3 (at 24 weeks after last dose of tanezumab or placebo matched to tanezumab)

• Number of Participants With Clinically Significant Electrocardiogram (ECG) Assessments

  Electrocardiogram assessment included PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF), QT interval corrected using Bazett's formula (QTcB), RR intervals, and heart rate. Investigator judged clinical significance of electrocardiogram assessment.

  Baseline up to Week 16

• Percentage of Participants With Individual Adjudicated Joint Safety Outcome/Event

  Percentage of participants with individual joint safety adjudication outcomes: rapidly progressive osteoarthritis (OA) type-1 only, rapidly progressive OA type-2 only, primary osteonecrosis, pathological fracture and subchondral insufficiency fracture is reported. Rapidly progressive (RP) OA type 1 events were those that the adjudication committee considered to have significant loss of joint space width \>= 2 millimeter within approximately 1 year without gross structural failure. RP OA type 2 events were those considered to have destruction of bone including limited or total collapse of at least 1 subchondral surface that is not normally present in conventional end-stage osteoarthritis. Subchondral insufficiency fractures are a type of stress fractures which occur below the cartilage on the weight bearing surface of a bone.

  Baseline up to Week 80

• Observation Time-Adjusted Event Rate for an Individual Adjudicated Joint Safety Outcome/Event

  Individual adjudicated joint safety outcomes/event: rapidly progressive OA (type-1,type-2), primary osteonecrosis, pathological fracture and subchondral insufficiency fracture. Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Event rate for any individual adjudicated joint safety outcome/event = the number of events per 1000 participant-years at risk.

  Baseline (Day 1) up to Week 80

• Percentage of Participants With At Least 1 Total Joint Replacement

  Percentage of participants with at least 1 total knee, total hip or total shoulder joint replacement were reported.

  Baseline (Day 1) up to Week 80

• Observation Time-Adjusted Event Rate for Total Joint Replacement (TJR) Event

  Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant had no TJR, or (ii) date of TJR (earliest TJR within each participant in the case of multiple TJRs). Event rate = number of events per 1000 participant-years at risk.

  Baseline (Day 1) up to Week 80

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 2

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 2

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 4

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 4

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 8

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 8

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 16

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 16

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 24

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 24

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 32

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 32

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 40

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 40

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 48

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 48

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 56

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 56

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 64

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 64

• Change From Baseline in Neuropathy Impairment Score (NIS) at Week 80

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

  Baseline, Week 80

• Largest Change From Baseline in Neuropathy Impairment Score (NIS) to Any Post-baseline Visit

  NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits. Largest change from baseline here means worst post- baseline change value (among all change from baseline values).

  Baseline to any post-baseline visit (until Week 80)

• Number of Participants With Anti Tanezumab Antibodies From Baseline up to Week 80

  Human serum samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a validated analytical method. Number of participants with presence of anti-tanezumab antibodies are reported.

  Baseline up to Week 80

• Number of Participants With Abnormal Physical Examination Findings

  Physical examination included assessment of general appearance, skin, head, neck, eyes, ears, nose, throat, abdomen, lungs, heart, thyroid, and extremities. Investigator judged abnormality in physical examinations. Only those rows have been reported which had at least 1 participant with abnormality data in any of the reporting arms.

  At Screening

Secondary Outcomes (40)

• Change From Baseline in Average Low Back Pain Intensity (LBPI) at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56: Multiple Imputation

  Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56

• Change From Baseline in Average Low Back Pain Intensity (LBPI) at Week 64: Observed Data

  Baseline, Week 64

• Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Scores at Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 56: Multiple Imputation

  Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56

• Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 64: Observed Data

  Baseline, Week 64

• Change From Baseline in the Patient's Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64

  Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64

Study Arms (3)

Celecoxib

ACTIVE COMPARATOR

Subcutaneous injection of placebo for tanezumab every 8 weeks plus oral celecoxib 100 mg twice daily for 56 weeks

Drug: Celecoxib; Biological: Placebo for tanezumab

Tanezumab 5 mg

EXPERIMENTAL

Subcutaneous injection of tanezumab 5 mg every 8 weeks plus oral placebo for celecoxib twice daily for 56 weeks

Biological: Tanezumab 5 mg; Drug: Placebo for celecoxib

Tanezumab 10 mg

EXPERIMENTAL

Subcutaneous injection of tanezumab 10 mg every 8 weeks plus oral placebo for celecoxib twice daily for 56 weeks

Biological: Tanezumab 10 mg; Drug: Placebo for celecoxib

Interventions

Celecoxib DRUG

Orally administered Celecoxib 100 mg twice daily for 56 weeks

Celecoxib

Tanezumab 5 mg BIOLOGICAL

Subcutaneous injection of tanezumab 5 mg every 8 weeks for 56 weeks

Tanezumab 5 mg

Tanezumab 10 mg BIOLOGICAL

Subcutaneous injection of tanezumab 10 mg every 8 weeks for 56 weeks

Tanezumab 10 mg

Placebo for celecoxib DRUG

Orally administered the placebo twice daily for 56 weeks

Tanezumab 10 mg; Tanezumab 5 mg

Placebo for tanezumab BIOLOGICAL

Subcutaneous injection of the placebo every 8 weeks for 56 weeks

Celecoxib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Duration of chronic low back pain for ≥3 months, and treatment with agents for low back pain for ≥3 months.
• Primary location of low back pain must be between the 12th thoracic vertebra and the lower gluteal folds, with or without radiation into the posterior thigh, classified as Category 1 or 2 according to the classification of the Quebec Task Force in Spinal Disorders.
• Subjects must be experiencing some benefits from their current stable dose regimen of oral NSAID (celecoxib, loxoprofen or meloxicam) treatment as described in the protocol, be tolerating their NSAID regimen, be taking this medication regularly during the 30 day period prior to the Screening visit and must have had some improvement in low back pain, but still require additional pain relief at Screening.
• Subjects must maintain a stabilized, protocol specified NSAID dose regimen for at least the final 2 or 3 weeks of the Screening period.
• Low Back Pain Intensity (LBPI) score of ≥5 at Screening.
• Subjects must be willing to discontinue all pain medications for chronic low back pain except rescue medication and investigational product and not use prohibited pain medications throughout the duration of the study.
• Female subjects of childbearing potential and at risk for pregnancy must agree to comply with protocol specified contraceptive requirements.

You may not qualify if:

• Subjects exceeding protocol defined BMI limits.
• Diagnosis of osteoarthritis of the knee or hip as defined by the ACR combined clinical and radiographic criteria.
• Subjects who have Kellgren Lawrence Grade \> or =2 radiographic evidence of hip or Grade \> or =3 radiographic evidence of knee osteoarthritis will be excluded.
• Subjects who have Kellgren Lawrence Grade \< or =2 radiographic evidence of knee osteoarthritis but who do not meet ACR criteria and do not have pain associated with their knee osteoarthritis will be allowed.
• Subjects with symptoms and radiologic findings consistent with osteoarthritis in the shoulder.
• History of lumbosacral radiculopathy within the past 2 years, history of spinal stenosis associated with neurological impairment, or history of neurogenic claudication.
• Back pain due to recent major trauma within 6 months prior to Screening.
• Surgical intervention during the past 6 months for the treatment of low back pain.
• Planned surgical procedure during the duration of the study.
• History or radiographic evidence of other diseases that could confound efficacy or safety assessments (eg, rheumatoid arthritis).
• History or radiographic evidence of orthopedic conditions that may increase the risk of, or confound assessment of joint safety conditions during the study.
• History of osteonecrosis or osteoporotic fracture.
• History of significant trauma or surgery to a knee, hip, or shoulder within the previous year.
• Signs or symptoms of carpal tunnel syndrome in the one year prior to Screening.
• Considered unfit for surgery based upon American Society of Anesthesiologists physical classification system for surgery grading, or subjects who would not be willing to undergo joint replacement surgery if required.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (55)

Meitoh Hospital

Nagoya, Aichi-ken, 465-0025, Japan

Location

Asahi Rosai Hospital

Owariasahi, Aichi-ken, 488-8585, Japan

Location

Asahi General Hospital

Asahi, Chiba, 289-2511, Japan

Location

Sato Orthopedic Clinic

Ichikawa, Chiba, 272-0021, Japan

Location

Fukuoka Mirai Hospital

Higashi-ku,Fukuoka, Fukuoka, 813-0017, Japan

Location

Shinkokura Hospital

Kitakyushu, Fukuoka, 803-8505, Japan

Location

Kyushu Rosai Hospital

Kokuraminami-ku,Kitakyushu, Fukuoka, 800-0296, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, 830-0011, Japan

Location

Shin Komonji Hospital

Moji-ku, Kitakyusyu, Fukuoka, 800-0057, Japan

Location

Fujita general Hospital

Date-gun, Fukushima, 969-1793, Japan

Location

Shirakawa Hospital

Shirakawa, Fukushima, 961-0092, Japan

Location

Toyooka Chuo Hospital

Asahikawa, Hokkaido, 078-8237, Japan

Location

Hakodate Central General Hospital

Hakodate, Hokkaido, 040-8585, Japan

Location

Hakodate Ohmura Orthopedic Hospital

Hakodate, Hokkaido, 041-0802, Japan

Location

Okubo Hospital

Akashi, Hyōgo, 674-0051, Japan

Location

Omuro Orthopedic Clinic

Himeji, Hyōgo, 670-0976, Japan

Location

Medical corporate corporation hoshikai Onishi medical clinic

Kako-gun, Hyōgo, 675-1115, Japan

Location

Kobe Red Cross Hospital

Kobe, Hyōgo, 651-0073, Japan

Location

Nishinomiya Municipal Central Hospital

Nishinomiya, Hyōgo, 663-8014, Japan

Location

National Hospital Organization Kanazawa Medical Center

Kanazawa, Ishikawa-ken, 920-8650, Japan

Location

Morita Hospital

Komatsu, Ishikawa-ken, 923-8507, Japan

Location

Sagamidai Hospital

Zama, Kanagawa, 252-0001, Japan

Location

Misugikai Medical Corporation Otokoyama Hospital

Yawata, Kyoto, 614-8366, Japan

Location

National Hospital Organization Matsumoto Medical Center

Matsumoto, Nagano, 399-8701, Japan

Location

Yodakubo Hospital

Nagawa-machi, Chisagata-gun, Nagano, 386-0603, Japan

Location

National Hospital Organization Beppu Medical Center

Beppu, Oita Prefecture, 874-0011, Japan

Location

National Hospital Organization Osaka Minami Medical Center

Kawachi-Nagano, Osaka, 586-8521, Japan

Location

Kishiwada Tokushukai Hospital

Kishiwada, Osaka, 596-8522, Japan

Location

Osaka Rosai Hospital

Sakai, Osaka, 591-8025, Japan

Location

Nagayama Hospital

Sennan-gun, Osaka, 590-0406, Japan

Location

Saiseikai Kawaguchi General Hospital

Kawaguchi, Saitama, 332-8558, Japan

Location

Hanazono Orthopedics and Internal Medicine

Tokorozawa, Saitama, 359-0047, Japan

Location

Japanese Red Cross Hamamatsu Hospital

Hamamatsu, Shizuoka, 434-8533, Japan

Location

Iwata City Hospital

Iwata, Shizuoka, 438-8550, Japan

Location

Tokyo Saiseikai Central Hospital

Minato-ku, Tokyo, 108-0073, Japan

Location

Kitasato University Kitasato Institute Hospital

Minato-ku, Tokyo, 108-8642, Japan

Location

National Hospital Organization Murayama Medical Center

Musashimurayama, Tokyo, 208-0011, Japan

Location

Gate Town Hospital

Nerima-ku, Tokyo, 177-0051, Japan

Location

Juntendo University Nerima Hospital

Nerima-ku, Tokyo, 177-8521, Japan

Location

Nishikamata Orthopedic

Ōta-ku, Tokyo, 146-0094, Japan

Location

AR-Ex Oyamadai Orthopedic

Setagaya-ku, Tokyo, 158-0082, Japan

Location

Kohno Clinical Medicine Research Institute Daisan Kitashinagawa Hospital

Shinagawa-ku, Tokyo, 140-0001, Japan

Location

Ohimachi Orthopaedic Clinic

Shinagawa-ku, Tokyo, 140-0014, Japan

Location

Ogikubo Hospital

Suginami-ku, Tokyo, 167-0035, Japan

Location

Medical Corporation Keiyukai Masumoto Orthopedic Clinic

Suginami-ku, Tokyo, 167-0051, Japan

Location

Daido Hospital

Toshima-ku, Tokyo, 171-0033, Japan

Location

Tonami General Hospital

Tonami, Toyama, 939-1395, Japan

Location

Wakayama Medical University Kihoku Hospital

Ito-gun, Wakayama, 649-7113, Japan

Location

Shimonoseki City Hospital

Shimonoseki-shi, Yamaguchi, 750-8520, Japan

Location

Akita University Hospital

Akita, 010-8543, Japan

Location

Kuroda Orthopedic Hospital

Fukuoka, 814-0165, Japan

Location

Fukushima Medical University Hospital

Fukushima, 960-1295, Japan

Location

Morimoto Clinic

Osaka, 530-0041, Japan

Location

Nagayoshi General Hospital

Osaka, 547-0016, Japan

Location

Saitama Municipal Hospital

Saitama, 336-8522, Japan

Location

Related Publications (1)

• Konno SI, Nikaido T, Markman JD, Ohta M, Machida T, Isogawa N, Yoshimatsu H, Viktrup L, Brown MT, West CR, Verburg KM. Tanezumab for chronic low back pain: a long-term, randomized, celecoxib-controlled Japanese Phase III safety study. Pain Manag. 2022 Apr;12(3):323-335. doi: 10.2217/pmt-2021-0040. Epub 2021 Nov 17.

  PMID: 34786956 DERIVED

Related Links

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

MeSH Terms

Conditions

Low Back Pain; Chronic Pain

Interventions

Celecoxib; tanezumab

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2016
• First Posted: April 1, 2016
• Study Start: May 26, 2016
• Primary Completion: June 11, 2019
• Study Completion: June 11, 2019
• Last Updated: August 11, 2020
• Results First Posted: August 11, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share

Locations

JP (55)