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Mitogens

Tanezumab

Tanezumab 10 mg SC administered on day 1 and Day 57 (± 4 days)

Placebo SC (to match tanezumab SC) administered on Day 1 and tanezumab 10 mg SC on Day 57 (± 4 days)

Placebo

Scott R Plotkin

The primary objective of this study is to determine whether the administration of tanezumab, an anti-nerve growth factor (NGF) antibody, improves pain relief in schwannomatosis patients receiving background non-NSAID therapy.

Schwannomatosis is characterized by the predisposition to develop multiple schwannomas and, less commonly, meningiomas. Pain is the most frequent symptom reported by these patients, with 68% experiencing chronic pain.

The investigators propose to test the efficacy and tolerability of tanezumab as a treatment for schwannomatosis patients with chronic pain who have had inadequate pain relief in a randomized, placebo-controlled trial, which could form the basis of a larger, randomized controlled trial in the future.

The study is designed with a total duration of 281 days (40 weeks) and will consist of four periods: Pre-treatment, Double-Blind Treatment, Single Arm Treatment, and 24-Week Safety Follow-up. The Pre-Treatment Period lasting up to 30 days, followed by a Double-Blind Treatment Period lasting up to 8 weeks, followed by a Single Arm Treatment Period lasting up to 8 weeks, and a 24-Week Safety Follow-Up Period ending with the End of Study Visit at Week 40.

Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis

A Phase 2 Randomized, Double-blind, Placebo-Controlled Study of the Analgesic Efficacy and Safety of the Subcutaneous Administration of the Anti-NGF Antibody Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis

Change in worst pain level during past week from baseline to week 8 measured by NRS-11

Frequency of AEs related to treatment with Tanezumab

Incidence of orthostatic hypotension using postural changes in blood pressure in addition to mean changes in postural blood pressure

Pfizer

Massachusetts General Hospital

Professor of Neurology

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Musculoskeletal Diseases

Neoplasm Metastasis

Multiple Myeloma

Neoplasms, Plasma Cell

Cancer Pain

Bone Neoplasms

Bone Marrow Diseases

Neoplastic Processes

Bone Diseases

Hematologic Diseases

Neurologic Manifestations

Central Nervous System Depressants

Analgesics, Opioid

Placebo matched to active treatment subcutaneously

Subcutaneous study treatment (tanezumab 20 mg or matched placebo) dosed at 8 week intervals.

Pfizer CT.gov Call Center

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.

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).

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In this outcome measure average daily opioid consumption was reported in milligram of morphine equivalent dose (mg of MED).

In this outcome measure average number of doses of rescue opioid consumption at specified time points were reported.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Number of participants with joint replacement surgery were reported.

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.

Eli Lilly and Company

Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set was evaluated.

Participants received placebo matched to tanezumab SC once every 8 weeks for 24 weeks.

Participants in this discontinued treatment arm, received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and completed their treatment before the amendment.

Tanezumab 10 mg

Participants in this treatment group had received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and after the amendment they continued remaining treatment with tanezumab 20 mg SC once every 8 weeks.

Tanezumab 10/20 mg

Participants received tanezumab 20 mg SC once every 8 weeks for 24 weeks.

Tanezumab 20 mg

Total

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The safety analysis set included all participants treated with tanezumab or placebo SC, including participants who received tanezumab 10 mg prior to protocol amendment 3.

Pfizer ClinicalTrials.gov Call Center

Change at Week 8: Analysis of covariance (ANCOVA) model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

The modified intent to treat (mITT) analysis set: participants randomized to tanezumab 20 mg or placebo SC, received at least 1dose of SC study medication. Multiple imputation method was applied. As planned summarized efficacy data for tanezumab 10 mg and 10/20 mg arms not reported; for these 2 arms individual values are reported. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8

Change at Week 1: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 4: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 6: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 12: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 1

Change at Week 2

Change at Week 4

Change at Week 6

Change at Week 12

Change at Week 16

Change at Week 24

The mITT analysis set: participants randomized to tanezumab 20 mg or placebo SC, received at least 1dose of SC study medication. Multiple imputation method was applied. As planned summarized efficacy data for tanezumab 10 mg and 10/20 mg arms not reported; for these 2 arms individual values are reported. Here, ''number analyzed'' signifies participants evaluable at specified time points.

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

Change at Week 1: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 4:ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 6: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 8: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 12: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

Change at Week 8

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

Change at Week 8: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.

The mITT analysis set: participants randomized to tanezumab 20 mg or placebo SC, received at least 1dose of SC study medication. Multiple imputation method was applied. As planned summarized efficacy data for tanezumab 10 mg and 10/20 mg arms not reported; for these 2 arms individual values are reported. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and ''number analyzed'' signifies participants evaluable at specified time points.

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

Change at Week 1: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

Change at Week 4: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

Change at Week 6: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

Change at Week 8: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

Change at Week 12: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.

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

Participant with non-index visceral cancer pain sites were less than 10, hence data was not collected and analysis was not performed for this outcome measure.

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

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

Week 1 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 1 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 1 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 2 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 2 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 2 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 2 Reduction \>=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 4 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 4 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 4 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 4 Reduction \>=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 6 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 6 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 6 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 6 Reduction \>=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 8 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 8 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 8 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 8 Reduction \>=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 12 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 12 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 12 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 12 Reduction \>=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 16 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 16 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 16 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 16 Reduction \>=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 24 Reduction \>=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 24 Reduction \>=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 24 Reduction \>=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 24 Reduction \>=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness).

Week 1: Reduction of >=30%

Week 1: Reduction of >=50%

Week 1: Reduction of >=70%

Week 2: Reduction of >=30%

Week 2: Reduction of >=50%

Week 2: Reduction of >=70%

Week 2: Reduction of >=90%

The mITT analysis set was analyzed. Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation Carried Forward (LOCF) imputation was applied. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and ''number analyzed'' signifies participants evaluable at specified time points.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis	NCT04163419	Schwannomatosis Pain	Tanezumab Placebo	18 Years -	Massachusetts General Hospital
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	NCT02609828	Bone Metastasis Cancer Pain	Tanezumab	18 Years -	Pfizer

Spots Global Cancer Trial Database for tanezumab

Every month we try and update this database with for tanezumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tanezumab

Every month we try and update this database with for tanezumab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tanezumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.