Long Term Safety Study of Tanezumab in Chronic Low Back Pain

Phase 2TerminatedNCT00924664

Pfizer849 enrolled

Overview

The purpose of this study is to investigate the safety and efficacy of tanezumab for chronic low back pain. Patients who were randomized and treated with study medication in a previous chronic low back pain "parent" study will be eligible to enroll in this safety extension study at the Preferred Rollover Time Point visit or at the Early Termination visit of the parent study upon discontinuation due to lack of efficacy.

This study was terminated on 30 November 2010 following a US FDA clinical hold for tanezumab chronic low back pain clinical studies which halted dosing and enrollment of patients on 19 July 2010 for potential safety issues.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

849

Conditions

Low Back Pain

Interventions

Tanezumab 20 mgBIOLOGICAL

Tanezumab 20 mg administered IV every 8 weeks for 3 administrations followed by SC administration every 8 weeks for 4 administrations over a period of 64 weeks

Tanezumab 10 mgBIOLOGICAL

Tanezumab 10 mg administered IV every 8 weeks for 3 administrations followed by SC administration every 8 weeks for 4 administrations over a period of 64 weeks

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Written informed consent prior to completing any of the study procedures. * Female patients must meet one of the following criteria: 1\) Female patients of non childbearing potential - Must be post menopausal, defined as women who are \>=45 years old with amenorrhea for 24 consecutive months (regardless of FSH levels), or women who are amenorrheic for at least 1 year AND have a serum Follicle Stimulating Hormone (FSH) level greater than 30 IU/L at Screening for the parent double blind CLBP study; or Must be surgically sterile, defined as having had a hysterectomy and/or bilateral oophorectomy. 2.) Female patients of child bearing potential: must not be pregnant or lactating, and must be abstinent or use adequate contraception (2 forms of birth control, one of which must be a barrier method), and must have a negative serum pregnancy test at Screening (within 30 days prior to Baseline) and a negative urine pregnancy test at Baseline prior to initial dosing * Male patients must agree that they and their female spouses / partners will use adequate contraception (2 forms of birth control, one of which must be barrier method) or be of non childbearing potential. * Females of child bearing potential and males must be willing to use approved methods of contraception from commencement of screening procedures until 16 weeks after the last dose of IV study medication. * Patient must be able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures * Patient has been treated in a parent tanezumab double blind CLBP study * Patient has completed the Preferred Rollover Time Point visit of the double blind CLBP parent study or has been withdrawn for lack of efficacy. At least eight weeks but no more than 12 weeks have elapsed since the last study medication infusion in the parent study. Patients are permitted to enter the extension study up to 12 weeks after their last dose of study medication in their parent study (or 4 weeks after the End of Treatment visit) Exclusion Criteria: * Failed screening in a parent tanezumab double blind CLBP study * Withdrawn from a parent tanezumab double blind CLBP study for an adverse event * Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to become pregnant during the course of clinical study * Use of any investigational medication within 30 days prior to Baseline (3 months for any investigational biological other than tanezumab) or plans to receive an investigational medication other than the study medication during the course of this study * Patients who exited the parent double blind CLBP study because of lack of compliance, protocol violation (including not meeting entrance criteria), no longer willing to participate (for reasons other than lack of efficacy), or were lost to follow up in the parent double blind study * Patients who were randomized into the parent study in violation of inclusion or exclusion criteria but who were not withdrawn from the parent study; * Any other condition, which in the opinion of the Investigator, would put the patient at increased safety risk or otherwise make the patient unsuitable for this study

Locations (149)

Outcomes

Primary Outcomes

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

AE: any untoward medical occurrence in participant who received study medication without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to 112 days after last dose that were absent before treatment in this study or that worsened relative to pretreatment state.

Time frame: Baseline up to 112 days after last dose of study treatment (up to 448 days)

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 4

NIS: 74 items, assess muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0-244, higher score=greater impairment.

Time frame: A4091012: Baseline, A4091039: Week 4

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 8

Time frame: A4091012: Baseline, A4091039: Week 8

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Pinnacle Research Group, LLC

Anniston, Alabama, United States

Pinnacle Research Group, Anniston Medical Clinic

Anniston, Alabama, United States

Pinnacle Research Group

Anniston, Alabama, United States

Simon Williamson Clinic, PC

Birmingham, Alabama, United States

Simon-Williamson Clinic, PC

Hueytown, Alabama, United States

Saadat Ansari, MD

Huntsville, Alabama, United States

Alabama Orthopaedic Clinic

Mobile, Alabama, United States

Horizon Research Group

Mobile, Alabama, United States

Phoenix Diagnostic Imaging

Chandler, Arizona, United States

Radiant Research - Phoenix Southeast

Chandler, Arizona, United States

...and 139 more locations

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 16

Time frame: A4091012: Baseline, A4091039: Week 16

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 24

Time frame: A4091012: Baseline, A4091039: Week 24

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 32

Time frame: A4091012: Baseline, A4091039: Week 32

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 40

Time frame: A4091012: Baseline, A4091039: Week 40

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 48

Time frame: A4091012: Baseline, A4091039: Week 48

Change From A4091012 (NCT00876187) Baseline in Neuropathy Impairment Score (NIS) at Week 56

Time frame: A4091012: Baseline, A4091039: Week 56

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 4

BPI-sf: 11-item self-report questionnaire consists of 5 questions, to assess severity and impact of pain on daily functions. Question/item 1-4 (Q1-Q4) measure impact of pain (worst, least, average, right now). Question 5 (Q5) consists of 7 items which measure level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item answered on 11-point scale ranging from 0 (no pain/interference) to 10 (pain as bad as you can imagine/completely interferes).

Time frame: A4091012: Baseline, A4091039: Week 4

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 8

Time frame: A4091012: Baseline, A4091039: Week 8

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 16

Time frame: A4091012: Baseline, A4091039: Week 16

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 24

Time frame: A4091012: Baseline, A4091039: Week 24

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 32

Time frame: A4091012: Baseline, A4091039: Week 32

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 40

Time frame: A4091012: Baseline, A4091039: Week 40

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 48

Time frame: A4091012: Baseline, A4091039: Week 48

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Scores (Worst, Least, Average, Right Now) at Week 56

Time frame: A4091012: Baseline, A4091039: Week 56

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 4

BPI-sf: 11-item self-report questionnaire consists of 5 questions, assess severity and impact of pain on daily functions. Q1-Q4 measure impact of pain (worst, least, average, right now). Q5 (7 items) measure level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item answered on 11-point scale ranging from 0 (no pain/interference) to 10 (pain as bad as you can imagine/completely interferes). 7 items in Q5 averaged to obtain function composite score, range: 0 to 10; higher score=greater impairment.

Time frame: A4091012: Baseline, A4091039: Week 4

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 8

Time frame: A4091012: Baseline, A4091039: Week 8

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 16

Time frame: A4091012: Baseline, A4091039: Week 16

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 24

Time frame: A4091012: Baseline, A4091039: Week 24

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 32

Time frame: A4091012: Baseline, A4091039: Week 32

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 40

Time frame: A4091012: Baseline, A4091039: Week 40

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 48

Time frame: A4091012: Baseline, A4091039: Week 48

Change From A4091012 (NCT00876187) Baseline in Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Scores (General Activity, Walking Ability, Normal Work, Sleep, Function Composite) at Week 56

Time frame: A4091012: Baseline, A4091039: Week 56

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 4

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score was calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 4

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 8

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 8

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 16

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 16

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 24

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 24

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 32

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 32

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 40

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 40

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 48

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 48

Change From A4091012 (NCT00876187) Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 56

RMDQ: back-specific, participant administered questionnaire that assess how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements checked. Total possible RMDQ score: 0 to 24, with higher scores indicated greater disability.

Time frame: A4091012: Baseline, A4091039: Week 56

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 4

Participants answered: "Considering all ways your low back pain affects you, how are you doing today?" Participants rated their condition using scale assessing symptoms and limitations to carry out normal daily activities. Score range: 1-5. 1: Very Good (No symptoms and limitations); 2: Good (Mild symptoms and no limitations); 3: Fair (Moderate symptoms and some limitations); 4: Poor (Severe symptoms and inability to carry out most activities); 5: Very Poor (Very severe, intolerable symptoms and inability to carry all activities).

Time frame: A4091012: Baseline, A4091039: Week 4

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 8

Time frame: A4091012: Baseline, A4091039: Week 8

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 16

Time frame: A4091012: Baseline, A4091039: Week 16

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 24

Time frame: A4091012: Baseline, A4091039: Week 24

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 32

Time frame: A4091012: Baseline, A4091039: Week 32

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 40

Time frame: A4091012: Baseline, A4091039: Week 40

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 48

Time frame: A4091012: Baseline, A4091039: Week 48

Change From A4091012 (NCT00876187) Baseline in Patient Global Assessment of Low Back Pain at Week 56

Time frame: A4091012: Baseline, A4091039: Week 56

Secondary Outcomes

Time to Discontinuation Due to Lack of Efficacy

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

Time frame: Baseline up to Week 56

Plasma Concentration of Tanezumab

Analysis was done by setting concentration values below the lower limit of quantification (LLOQ) to zero.

Time frame: Baseline (Day 1), Week 8, 24, 40, 56, 64

Total Nerve Growth Factor (NGF) Concentration

Time frame: Baseline (Day 1), Week 8, 24, 40, 56, 64