A Phase 3 Study of Tanezumab for Chronic Low Back Pain

This study will investigate the efficacy and safety of tanezumab 5 mg and 10 mg administered by subcutaneous injection seven times at 8 week intervals (56 weeks). The primary objective of this study is to evaluate the effectiveness of tanezumab 10 mg and 5 mg compared to placebo for the treatment of chronic low back pain. Secondary objectives are to evaluate the long-term safety and effectiveness of tanezumab 10 mg and 5 mg compared to placebo for the treatment of chronic low back pain. In addition, the study will evaluate the effectiveness and long term safety profile of tanezumab treatment for chronic low back pain compared to tramadol Prolonged Release (PR), a medication commonly utilized for the treatment of chronic low back pain.

This is a randomized, double blind, placebo and active controlled, multicenter, parallel group Phase 3 study of the efficacy and safety of tanezumab when administered by SC injection for up to 56 weeks in subjects with chronic low back pain. Approximately 1800 subjects will be randomized to 1 of 4 treatment groups in a 2:2:2:3 ratio (ie, 400 subjects per treatment group for the placebo, tanezumab 5 mg and tanezumab 10 mg treatment groups and 600 subjects in the tramadol PR treatment group). Treatment groups will include: 1.) Placebo administered SC at an 8 week interval plus placebo matching tramadol PR up to Week 16. At the Week 16 visit, subjects in this group who meet the efficacy responder criteria will be switched in a blinded fashion in a 1:1 ratio to either tanezumab 5 mg or tanezumab 10 mg administered SC at an 8 week interval plus placebo matching tramadol PR to Week 56; 2.)Tanezumab 5 mg SC administered at an 8 week interval plus placebo matching tramadol PR to Week 56; 3.) Tanezumab 10 mg SC administered at an 8 week interval plus placebo matching tramadol PR to Week 56; 4.) Oral tramadol PR plus placebo administered SC at an 8 week interval to Week 56. The study is designed with a total duration (post randomization) of up to 80 weeks and will consist of three periods: Screening (up to a maximum of 37 days; includes a Washout Period and an Initial Pain Assessment Period), a Double blind Treatment Period (comprised of a 16 week Primary Efficacy Phase and a 40 week Long Term Safety and Efficacy Phase), and a Follow up Period (24 weeks). The Screening Period (beginning up to 37 days prior to Randomization) includes a Washout Period (lasting 2 32 days), if required, and an Initial Pain Assessment Period (the 5 days prior to Randomization/Baseline). Prior to entering the study, subjects must have a documented history of previous inadequate treatment response to medications in 3 different categories of agents commonly used to treat and generally considered effective for the treatment of chronic low back pain.

Eligibility Criteria:
Inclusion Criteria:

-Chronic low back pain ≥3 months in duration, Quebec Task Force in Spinal Disorders class 1 or 2, with documented history of previous inadequate treatment response to at least 3 different categories of agents commonly used and generally considered effective for the treatment of chronic low back pain.

Exclusion Criteria:

--Diagnosis of osteoarthritis of the knee or hip as defined by the American College of Rheumatology (ACR) criteria.

* Subjects who have Kellgren Lawrence Grade \> or =2 radiographic evidence of hip or Grade \> or=3 radiographic evidence of knee osteoarthritis will be excluded;
* History or radiographic evidence of other diseases that could confound efficacy or safety assessments (e.g., rheumatoid arthritis).
* History or radiographic evidence of orthopedic conditions that may increase the risk of, or confound assessment of joint safety conditions during the study.
* Signs and symptoms of clinically significant cardiac disease within 6 months of the study (e.g., unstable angina, myocardial infarction, resting bradycardia, poorly controlled or untreated hypertension) as defined in the protocol or subjects with any other cardiovascular illness that in the opinion of the Investigator would render a subject unsuitable to participate in the study
* History, diagnosis, or signs and symptoms of clinically significant neurological disease (e.g., transient ischemic attack, stroke, peripheral or autonomic neuropathy) as specified in the protocol
* Subjects with evidence or symptoms consistent with autonomic dysfunction (e.g., orthostatic hypotension and/or autonomic symptoms) as defined in the protocol.