Phase 3 Study on the Efficacy and Safety of Tanezumab in Patients With Cancer Pain Due to Bone Metastasis Who Are Taking Background Opioid Therapy

• ClinicalTrials.gov Identifier: NCT02609828
• Recruitment Status: Completed
• First Posted: November 20, 2015
• Results First Posted: January 20, 2023
• Last Update Posted: February 16, 2023
• Sponsor: Pfizer
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

The purpose of this study is to determine whether tanezumab is effective in the treatment of cancer pain due to bone metastasis in patients already taking background opioid therapy.

Condition or disease	Intervention/treatment	Phase
Bone Metastasis; Cancer Pain	Drug: Tanezumab	Phase 3

Detailed Description:

This is a randomized, double-blind, placebo-controlled, multicenter, parallel-group Phase 3 study in cancer subjects requiring treatment with background opioids for pain due to bone metastasis.

Approximately 144 subjects will be randomized to one of 2 treatment groups in a 1:1 ratio (approximately 72 subjects per group). Subjects will receive a total of 3 subcutaneous injections, separated by 8 weeks in addition to background opioids administered throughout the study.

Treatment groups will include: 1. Placebo SC (matching tanezumab SC) in addition to background opioid therapy. 2. Tanezumab 20 mg SC in addition to background opioid therapy.

The study consists of three periods: Pre-Treatment (up to 37 days), Double-Blind Treatment (24 weeks) and Safety Follow-up (24 weeks).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB (PF-04383119) IN SUBJECTS WITH CANCER PAIN PREDOMINANTLY DUE TO BONE METASTASIS RECEIVING BACKGROUND OPIOID THERAPY
• Actual Study Start Date: October 28, 2015
• Actual Primary Completion Date: September 17, 2020
• Actual Study Completion Date: June 25, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1; Tanezumab 20 mg subcutaneously	Drug: Tanezumab; Subcutaneous study treatment (tanezumab 20 mg or matched placebo) dosed at 8 week intervals.; Other Name: PF-04383119
Placebo Comparator: Arm 2; Placebo matched to active treatment subcutaneously	Drug: Tanezumab; Subcutaneous study treatment (tanezumab 20 mg or matched placebo) dosed at 8 week intervals.; Other Name: PF-04383119

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8 [ Time Frame: Baseline, Week 8 ]
   Daily average pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The participants recorded their daily average pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on interactive response technology (IRT) diaries. Baseline daily average pain intensity value was mean of the daily average pain intensity NRS scores during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Week 8 daily average pain intensity value was the mean of the daily average pain intensity NRS scores recorded for each of the 7 days prior to the Week 8.

Secondary Outcome Measures :

1. Change From Baseline in the Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 12, 16 and 24 ]
   Daily average pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain) where higher scores signified more severity of pain. The participants recorded their daily average pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline daily average pain intensity value was mean of the daily average pain intensity NRS scores during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Weeks 1, 2, 4, 6, 12, 16 and 24 daily average pain intensity value was the mean of the daily average pain intensity NRS scores recorded for each of the 7 days prior to the each specified week.
2. Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
   Daily worst pain intensity in the index bone metastasis cancer pain site is assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), higher scores signified more severity of pain. The participants describe their daily worst pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline daily worst pain intensity was mean of daily worst pain intensity NRS score during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 daily worst pain intensity value was the mean of the daily worst pain intensity NRS scores recorded for each of the 7 days prior to the each specified week.
3. Change From Baseline in the Weekly Average Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
   Weekly average pain intensity in the non-index cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. Non-index cancer pan sites were the most painful cancer pain sites other than the index bone metastasis cancer pain site. The participants described their weekly pain at the painful site by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline weekly average pain intensity was weekly average pain intensity NRS score recorded on any day during the baseline assessment period. Five days prior to dosing was considered as baseline assessment period. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 weekly average pain intensity value was the weekly average pain intensity NRS scores recorded on any day from the span of 7 days prior to specified week.
4. Change From Baseline in the Weekly Worst Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
   Weekly worst pain intensity in the non-index cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), higher scores signified more severity of pain. Non-index cancer pan sites were the most painful cancer pain sites other than the index bone metastasis cancer pain site. The participants describe their weekly worst pain at the painful site by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline weekly worst pain intensity was weekly worst pain intensity NRS score recorded on any day during the baseline assessment period. Five days prior to dosing was considered as baseline assessment period. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 weekly worst pain intensity value was the weekly worst pain intensity NRS scores which was recorded on any day from the span of 7 days prior to specified week.
5. Change From Baseline in the Daily Average Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
   Daily average pain intensity in the non-index visceral cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The participants described their pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline is defined as the mean average daily pain intensity NRS score during the baseline assessment period prior to randomization. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value is the mean of the daily average pain intensity scores for the 7 days prior to the each specified week.
6. Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
   Daily worst pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The participants recorded their daily worst pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline pain intensity value was mean of the daily worst pain intensity NRS scores during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value is the mean of the daily worst pain intensity scores for the 7 days prior to the each specified week.
7. Number of Participants With Cumulative Reduction of >=30, 50, 70 and 90 Percent (%) From Baseline in Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
   Daily average pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores = more severity of pain. The participants recorded their daily average pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value = mean of the daily average pain intensity NRS scores for the 7 days prior to the each week. Number of participants with cumulative reduction of >= 30, 50, 70, and 90 % in daily average pain intensity NRS score in the index bone metastasis cancer pain site from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 were reported. Participants might be reported more than once in the specified rows for a time point. Rows with only non-zero data for cumulative reduction at specified time points, for at least 1 reporting arm, are reported below.
8. Number of Participants With Reduction of >=30, 50, 70 and 90% From Baseline in Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
   Daily worst pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores = more severity of pain. The participants recorded their daily worst pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value = mean of the daily worst pain intensity NRS scores for the 7 days prior to the each week. Number of participants with cumulative reduction of >= 30, 50, 70, and 90 % in daily worst pain intensity NRS score in the index bone metastasis cancer pain site from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 were reported. Participants might be reported more than once in the specified rows for a time point. Rows with only non-zero data for cumulative reduction at specified time points, for at least 1 reporting arm, are reported below.
9. Change From Baseline in Participant's Global Assessment of Cancer Pain (PGA-CP) at Weeks 2, 4, 8, 16 and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 16 and 24 ]
   Participants at specified time points, answered to the following question, "Considering all the ways your cancer pain affects you, how are you doing today?" on a Likert scale ranging from 1 to 5, on IRT diaries. Scores: 1= very good (asymptomatic and no limitation of normal activities); 2= good (mild symptoms and no limitation of normal activities); 3= fair (moderate symptoms and limitation of some normal activities); 4= poor (severe symptoms and inability to carry out most normal activities); and 5= very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher scores signified worsening of condition.
10. Number of Participants With Reduction of >=2 Points From Baseline in PGA-CP Scores at Weeks 2, 4, 8, 16 and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 16 and 24 ]
    Participants at specified time points, answered to the following question, "Considering all the ways your cancer pain affects you, how are you doing today?" on a Likert scale ranging from 1 to 5, on IRT diaries. Scores:1= very good (asymptomatic and no limitation of normal activities); 2= good (mild symptoms and no limitation of normal activities); 3= fair (moderate symptoms and limitation of some normal activities); 4= poor (severe symptoms and inability to carry out most normal activities); and 5= very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher scores signified worsening of condition.
11. Average Daily Total Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
    In this outcome measure average daily opioid consumption was reported in milligram of morphine equivalent dose (mg of MED).
12. Average Number of Doses of Rescue Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16 and 24 ]
    In this outcome measure average number of doses of rescue opioid consumption at specified time points were reported.
13. Change From Baseline in the Weekly Opioid-Related Symptom Distress Scale (OR-SDS) at Weeks 2, 4, 8, 16, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 16, and 24 ]
    OR-SDS: questionnaire evaluated opioid-related 12 symptoms. For each symptom, participants assigned integer scores to assess severity (none =0 to very severe =4), distress (none =0 to very much =5), and frequency (none =0 to almost constantly =4; participants reported number of retching/vomiting episodes (none =0, 1-2 episodes =1, 3-4 episodes =2, 5-6 episodes =3, >6 episodes =4). Frequency composite score: mean of frequency scores from all symptoms, ranged from 0 (none) to 4 (almost constantly); higher scores = worse condition. Severity composite score: mean of severity scores from all 12 symptoms, ranged from 0 (none) to 4 (maximum severity); higher scores = worse condition. Distress composite score: mean of distress scores from all 12 symptoms, ranged from 0 (none) to 5 (maximum distress); higher scores = worse condition. Multi domain average (MDA): average of each symptom for frequency, severity, and distress; ranged from 0 (none) to 4.34 (worse); higher scores = worse condition.
14. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 of dosing up to 24 weeks post last dose (maximum up to Week 48) ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (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 post last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs. Participants were followed up to 24 weeks after study drug last dose.
15. Number of Participants With Laboratory Abnormalities (Normal Baseline) [ Time Frame: Baseline (Day 1, before dosing) up to Week 48 ]
    Laboratory 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; leukocytes<0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN; basophils, eosinophils, monocytes >1.2*ULN; total bilirubin>1.5*ULN; activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio >1.1*ULN; bilirubin >1.5*ULN; aspartate aminotransferase (AT), alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase >3.0*ULN; protein; albumin<0.8*LLN, >1.2*ULN; 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; Urine: glucose, ketones, protein, HGB, bilirubin, nitrite >=1.
16. Number of Participants With Laboratory Abnormalities (Abnormal Baseline) [ Time Frame: Baseline (Day 1, before dosing) up to Week 48 ]
    Laboratory abnormality criteria included: HGB; hematocrit; erythrocytes < 0.8* 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; leukocytes <0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN; basophils, eosinophils, monocytes >1.2*ULN; activated partial thromboplastin time, prothrombin time >1.1*ULN; bilirubin>1.5*ULN; aspartate AT, alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase >3.0*ULN; protein; albumin<0.8*LLN, >1.2*ULN; urea nitrogen, 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; creatine kinase >2.0*ULN.
17. Number of Participants With Categorical Change From Baseline to Last Post-Baseline in Sitting Systolic and Diastolic Blood Pressure During Treatment Period [ Time Frame: Baseline (Day 1, before dosing) up to Week 24 ]
    Change categories for sitting systolic blood pressure measured in millimeter of mercury (mm Hg) were as follows: change <=-40, change >-40 to -30, change >-30 to -20, change >-20 to -10, change >-10 to 0, change >0 to <10, change >=10 to <20, change >=20 to <30, change >=30 to <40 and change >=40. Change categories for sitting diastolic blood pressure measured in mm Hg were as follow: change <=-30, change >-30 to -20, change >-20 to -10, change >-10 to 0, change >0 to <10, change >=10 to <20, change >=20 to <30 and change >=30. Rows with only non-zero data/values, for at least 1 reporting arm, are reported below.
18. Number of Participants With Categorical Summary of Electrocardiogram (ECG) (QTC) Data [ Time Frame: Baseline (Day 1, before dosing) up to Week 24 ]
    Electrocardiogram assessment included QT interval corrected using Fridericia's formula (QTcF), QT interval corrected using Bazett's formula (QTcB), both had following categories: 450<=Value<480 millisecond (msec), 480<=Value<500 msec and Value>=500 msec.
19. Number of Participants With Confirmed Orthostatic Hypotension [ Time Frame: Baseline (Day 1, before dosing), Weeks 8, 16, 24 and 48 ]
    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.
20. Number of Participants With Clinically Significant Findings in Weight Measurement, Counted as an AE [ Time Frame: Day 1 of dosing up to maximum of Week 48 ]
    The number of participants with clinically significant findings in weight measurement and were counted as an AE in the study were reported in this outcome measure.
21. Number of Participants With Abnormal Physical Examination at Screening [ Time Frame: Screening (up to 37 days prior to Day 1) ]
    Physical examination included assessment of general, head, eyes, ears, nose, neck, thyroid, lungs, heart, abdomen, extremities, skin, throat and other. Investigator judged abnormality in physical examinations.
22. Number of Participants With Individual Adjudicated Joint Safety Outcome/Event [ Time Frame: During the study, maximum up to Week 48 ]
    Joint-related safety events resulting in total joint replacement and/or discontinuation from the study as well as adverse events were reviewed by the External Adjudication Committee to confirm the potential events as adjudicated join safety event. In this outcome measure, number of participants with any of the joint safety adjudication outcomes of primary osteonecrosis, rapidly progressive osteoarthritis (OA) (type 1 and type 2), subchondral insufficiency fracture (or SPONK), or pathological fracture were reported. Other adjudication outcomes included normal progression of OA and other joint outcome.
23. Number of Participants With At Least 1 Total Joint Replacements (TJR) [ Time Frame: During the study, maximum up to Week 48 ]
    Number of participants with joint replacement surgery were reported.
24. Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Anti-Drug Antibodies (NAb) [ Time Frame: Baseline (Day 1, before dosing) up to Week 48 ]
    Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA). Number of participants with presence of anti-tanezumab antibodies and neutralizing anti-drug antibodies are reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Personally signed and dated informed consent document.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Male or female, ≥18 years of age
• Weight ≥40 kg at Screening
• Cancer diagnosed as having metastasized to bone or multiple myeloma.
• Imaging confirmation of bone metastasis at Screening or within 120 days prior to the Screening visit.
• Expected to require daily opioid medication throughout the course of the study.
• Willing to not use prohibited medications (including NSAIDs) throughout the duration of the study.
• Average Pain Score ≥5 at Screening for the index bone metastasis cancer pain site.
• Patient's Global Assessment of Cancer Pain of "fair", "poor" or "very poor" at Screening.
• Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0, 1, or 2 at Screening.
• Adequate bone marrow, renal and liver function at Screening.
• International Normalized Ratio (INR) or prothrombin time (PT) <1.5 x ULN at Screening unless being treated with anticoagulant medication.
• Females must either be not of childbearing potential or, if of childbearing potential and at risk for pregnancy, must be willing to use at least one highly effective method of contraception throughout the study and for 112 days (16 weeks) after the last dose of assigned subcutaneous study medication.

Exclusion Criteria:

• Pain related to an oncologic emergency.
• Brain metastasis or leptomeningeal metastasis.
• Presence of hypercalcemia at Screening.
• Pain primarily classified as not predominantly related to a bone metastasis.
• Systemic treatment for the primary malignancy or bone metastasis started within 30 days of the Baseline Assessment Period.
• Chemotherapies associated with peripheral neuropathy (ie, paclitaxel, docetaxel, oxaliplatin, cisplatin, vincristine, thalidomide or bortezomib) are prohibited during the study from 30 days prior to the first day of the Baseline Assessment Period to Week 48.
• Receipt of radiopharmaceutical treatment or radiotherapy for treatment of bone metastasis within 30 days of the Baseline Assessment Period.
• Concurrent adjuvant analgesics unless started at least 30 days prior to the start of the Baseline Assessment Period and maintained at a stable dose.
• Diagnosis of osteoarthritis of the knee or hip or findings consistent with osteoarthritis in the shoulder.
• History of significant trauma or surgery to a major joint within one year prior to Screening.
• History of osteonecrosis or osteoporotic fracture.
• X-ray evidence at Screening of: 1) rapidly progressive osteoarthritis, 2) atrophic or hypotrophic osteoarthritis, 3) subchondral insufficiency fracture, 4) spontaneous osteonecrosis of the knee (SPONK), 5) osteonecrosis, or 6) pathologic fracture.
• Signs and symptoms of clinically significant cardiac disease.
• Evidence of orthostatic hypotension at Screening or at Baseline prior to randomization.
• Diagnosis of a transient ischemic attack in the 6 months prior to Screening or diagnosis of stroke with significant residual deficits.
• History, diagnosis, or signs and symptoms of clinically significant neurological disease.
• Total impact score of >7 on the Survey of Autonomic Symptoms (SAS) at Screening.
• Past history of carpal tunnel syndrome (CTS) with signs or symptoms of CTS in the one year prior to Screening.
• History of significant alcohol, analgesic, or narcotic substance abuse within the six months prior to Screening.
• Planned surgical procedure during the duration of the study.
• Considered unfit for surgery or not willing to undergo joint replacement surgery if required.
• Known hypersensitivity to opioids or an underlying medical condition contraindicating opioid use.
• History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
• Previous exposure to exogenous nerve growth factor or to an anti-nerve growth factor antibody.
• Presence of drugs of abuse, prescription medications without a valid prescription or other illegal drugs at Screening.
• Positive Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) tests at Screening indicative of current infection.
• Investigational site staff members and their family members, or Pfizer employees directly involved in the conduct of the trial.
• Participation in other studies involving investigational drug(s) within 30 days (or 90 days for investigational biologics) before Baseline Assessment Period and/or during study participation.
• Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential who are unwilling or unable to use one (1) highly effective method of contraception throughout the study and for 112 days after last dose of investigational product.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality.

Contacts and Locations

Locations

Argentina

Instituto de Oncologia de Rosario

Rosario, Santa FE, Argentina, S2000KZE

Australia, Victoria

Monash Medical Centre

Clayton, Victoria, Australia, 3168

Monash Medical Centre

East Bentleigh, Victoria, Australia, 3165

Austria

Landesklinikum Krems

Krems, Austria, 3500

Nuhr Medical Center

Senftenberg, Austria, 3541

Brazil

Associacao Hospital de Caridade de Ijui

Ijui, RIO Grande DO SUL, Brazil, 98700-000

INCA - Instituto Nacional do Cancer / Hospital do Cancer HCIII

Rio de Janeiro, RJ, Brazil, 20560-120

Fundação Pio XII-Hospital de Cancer de Barretos

Barretos, SAO Paulo, Brazil, 14.784-400

Centro de Ensino e Pesquisa da Fundacao Amaral Carvalho

Jau, SAO Paulo, Brazil, 17210-120

Fundacao do ABC - Faculdade de Medicina do ABC - CEPHO

Santo Andre, SAO Paulo, Brazil, 09060-650

Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral

Itajai, SC, Brazil, 88.301-220

Fundacao do ABC-Faculdade de Medicina do ABC

Santo Andre, SP, Brazil, 09060-870

Hospital AC Camargo_Fundacao Antonio Prudente

Sao Paulo, SP, Brazil, 01509-900

Centro de Pesquisa Clinica do IBCC - Instituto Brasileiro de Controle do Cancer

Sao Paulo, SP, Brazil, 03102-006

Hospital AC Camargo_Fundacao Antonio Prudente

Sao Paulo, Brazil, 01509-900

Chile

James Lind Centro de lnvestigacion del Cancer

Araucania, Chile, 4800827

China, Anhui

The First Affiliated Hospital of Anhui Medical University, Department of Medical Oncology

Hefei, Anhui, China, 230022

China, Beijing

The Fifth Medical Center of PLA General Hospital

Beijing, Beijing, China, 100071

China, Chongqing

Daping Hospital, Research Institute of Surgery Third Military Medical University

Chongqing, Chongqing, China, 400042

China, Heilongjiang

Harbin Medical University Cancer Hospital/Oncology Department

Harbin, Heilongjiang, China, 150081

China, Henan

Henan Cancer Hospital/Respiration internal medicine

Zhengzhou, Henan, China, 450008

China, Hubei

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center

Wuhan, Hubei, China, 430030

Hubei Cancer Hospital

Wuhan, Hubei, China, 430079

China, Shanghai

Shanghai Sixth People's Hospital

Shanghai, Shanghai, China, 200233

China, Sichuan

Oncology Department, West China Hospital of Sichuan University

Chengdu, Sichuan, China, 610041

China, Zhejiang

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China, 310022

China

Tianjin Cancer Hospital

Tianjin, China, 300060

Czechia

Urocentrum Plzen Research Site s.r.o.

Plzen, Czechia, 30100

Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Centrum pro lecbu bolesti

Praha 2, Czechia, 128 00

Hungary

Veszprem Megyei Tudogyogyintezet Farkasgyepu

Farkasgyepu, Hungary, 8582

CRU Hungary Ltd., MISEK Hematology Department-CRU Co.

Miskolc, Hungary, 3529

CRU Hungary Ltd., MISEK-CRU

Miskolc, Hungary, 3529

Josa Andras Hospital, Clinical Research Department

Nyiregyhaza, Hungary, 4400

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz

Nyiregyhaza, Hungary, 4400

Help-MR Diagnosztika Kft.

Szekesfehervar, Hungary, 8000

Israel

HaEmek Medical Center

Afula, Israel, 1834111

Rambam Health Care Campus

Haifa, Israel, 3109601

Chaim Sheba Medical Center

Ramat Gan, Israel, 52621

Japan

National Hospital Organization Toyohashi Medical Center

Toyohashi, Aichi, Japan, 440-8510

National Cancer Center Hospital East

Kashiwa, Chiba, Japan, 277-8577

Gunma Prefectural Cancer Center

Ota, Gunma, Japan, 373-8550

Nishinomiya Municipal Central Hospital

Nishinomiya, Hyogo, Japan, 663-8014

The Hospital of Hyogo College of Medicine

Nishinomiya, Hyogo, Japan, 663-8501

Saga-Ken Medical Centre Koseikan

Saga, Japan, 840-8571

National Hospital Organization Tokyo Medical Center

Tokyo, Japan, 152-8902

Korea, Republic of

Clinical Trial Pharmacy, National Cancer Center

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

Imaging Facilities, National Cancer Center

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

National Cancer Center

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

Keimyung University Dongsan Medical Center

Daegu, Korea, Republic of, 42601

Clinical Trial Pharmacy, Severance Hospital

Seoul, Korea, Republic of, 03722

Imaging Facilities, Severance Hospital

Seoul, Korea, Republic of, 03722

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 03722

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Poland

Powiatowy Zespol Zakladow Opieki Zdrowotnej Oddzial Opieki Paliatywnej

Bedzin, Poland, 42-500

NZOZ Vitamed im. Edyty Jakubow

Bialystok, Poland, 15-215

Poradnia Otropedyczno-Urazowa; Gabient RTG

Bialystok, Poland, 15-437

Pracownia RTG Helimed

Czeladz, Poland, 41-250

Niepubliczny Zaklad Opieki Zdrowotnej, Zespol Medyczno-Opiekunczy Alicja Kluczna

Dabrowa Gornicza, Poland, 41-300

Hospicjum im. Ks. Eugeniusza Dutkiewicza SAC w Gdansku

Gdansk, Poland, 80-208

Stowarzyszenie Przyjaciol Chorych Hospicjum w Gliwicach NZOZ Hospicjum Milosierdzia Bozego

Gliwice, Poland, 44-100

Stowarzyszenie Przyjaciol Chorych Hospicjum w Gliwicach, NZOZ Hospicjum Milosierdzia Bozego

Gliwice, Poland, 44-100

Regionalny Szpital Specjalistyczny im. Dr. Wl.Bieganskiego, Oddzial Onkologii Klinicznej

Grudziadz, Poland, 86-300

SCANiX Sp.z o.o

Katowice, Poland, 40-057

NZOZ "Vegamed"

Katowice, Poland, 40-060

Helimed Diagnostic Imaging Sp. z o.o., Sp. komandytowa

Katowice, Poland, 40-760

Helimed Diagnostic Imaging Sp. z.o.o., Sp. komandytowa

Katowice, Poland, 40-760

Centrum Diagnostyki Obrazowej EPIONE

Katowice, Poland, 40-872

NZOZ Neuromed M. i M. Nastaj Sp. P.

Lublin, Poland, 20-064

SK Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu,

Poznan, Poland, 61-245

Klinika Nowotworow Piersi i Chirurgii Rekonstrukcyjnej w Centrum Onkologii -Instytucie

Warszawa, Poland, 02-781

Szpital LUX MED

Warszawa, Poland, 02-801

Romania

SC Oncolab SRL

Craiova, Dolj, Romania, 200385

S.C. Oncocenter Oncologie Clinica S.R.L.

Timisoara, Timis, Romania, 300166

Spitalul Clinic C.F. 2 Bucuresti. Departament Oncologie, Sectia Medicala 2

Bucuresti, Romania, 011464

Slovakia

Narodny onkologicky ustav

Bratislava, Slovakia, 833 10

DEMOMED s.r.o.

Nove Zamky, Slovakia, 94001

MUDr. Viliam Cibik, PhD, s.r.o.

Pruske, Slovakia, 018 52

Fakultna Nemocnica S Poliklinikou Zilina

Zilina, Slovakia, 012 07

Spain

Hospital General Universitario de Elche Servicio de Farmacia

Elche, Alicante, Spain, 03203

Hospital General Universitario de Elche

Elche, Alicante, Spain, 03203

Hospital Can Misses

Ibiza, Islas Baleares, Spain, 07800

Hospital General Universitario de Alicante

Alicante, Spain, 03010

Hospital Universitario de la Princesa

Madrid, Spain, 28006

Hospital La Moraleja

Madrid, Spain, 28050

Hospital Universitario HM Sanchinarro

Madrid, Spain, 28050

United Kingdom

St George's University Hospitals NHS Foundation Trust

Tooting, London, United Kingdom, SW17 0QT

NHS Lothian, Royal Infirmary of Edinburgh

Edinburgh, Scotland, United Kingdom, EH16 4SA

NHS Lothian, Western General Hospital

Edinburgh, Scotland, United Kingdom, EH4 2XU

NHS Lothian

Edinburgh, Scotland, United Kingdom, EH4 2XU

Sponsors and Collaborators

Pfizer

Eli Lilly and Company

Investigators

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

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] June 14, 2018

Statistical Analysis Plan  [PDF] January 8, 2021

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02609828
• Other Study ID Numbers: A4091061; 2013-002223-42 ( EudraCT Number ); CANCER PAIN PH 3 SC STUDY ( Other Identifier: Alias Study Number )
• First Posted: November 20, 2015
• Results First Posted: January 20, 2023
• Last Update Posted: February 16, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

Metastatic cancer bone pain; Multiple myeloma

Additional relevant MeSH terms:

Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases; Cancer Pain; Neoplastic Processes; Neoplasms; Pathologic Processes; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Hematologic Diseases; Pain; Neurologic Manifestations; Tanezumab; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs