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

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).

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.