Study of the Analgesic Efficacy and Safety of Subcutaneous Tanezumab in Subjects With Osteoarthritis of the Hip or Knee.
Condition: Osteoarthritis, Hip; Osteoarthritis, Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip
Intervention: Tanezumab; Tanezumab; Placebo
Intervention description: 2.5 mg; 5 mg; Placebo
Intervention MeSH terms: Tanezumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 849.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Osteoarthritis, pain, tanezumab.

Summary:

      Tanezumab is a monoclonal antibody that binds to and inhibits the actions of nerve growth
      factor (NGF). The Nerve Growth Factor Inhibitor (NGFI) class may offer an important
      breakthrough in the treatment of chronic pain and is under clinical investigation for the
      treatment of pain associated with osteoarthritis or other chronic pain conditions.

      The primary objective of this study is to demonstrate superior efficacy of tanezumab 5 mg and
      2.5 mg administered subcutaneously (SC) every 8 weeks versus placebo at Week 24 in subjects
      with osteoarthritis of the knee or hip. The 2.5 mg dose was shown to provide efficacy
      benefits with a favorable safety profile when administered intravenously in previous Phase 3
      clinical trials. The 5 mg dose is expected to provide added efficacy benefit over the 2.5 mg
      dose based on data from previous studies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A diagnosis of osteoarthritis of the index hip or knee based on American College of
             Rheumatology criteria with Kellgren Lawrence x-ray Grade of at least 2 as diagnosed by
             the Central Reader

          -  A history of insufficient pain relief from acetaminophen along with a history of
             insufficient pain relief from, inability to tolerate or contraindication to taking
             NSAIDs, and tramadol or opioid treatments.

          -  WOMAC Pain subscale score of at least 5 in the index hip or knee at Screening.

          -  Be willing to discontinue all non study pain medications for osteoarthritis and not
             use prohibited pain medications throughout the duration of the study.

          -  Female subjects of childbearing potential must agree to comply with protocol specified
             contraceptive requirements.

        Exclusion Criteria:

          -  Subjects exceeding protocol defined BMI or body weight limits.

          -  History of other diseases specified in the protocol (e.g. inflammatory joint diseases,
             crystalline diseases such as gout or pseudogout) that may involve the index joint and
             that could interfere with efficacy assessments.

          -  Radiographic evidence of protocol specified bone or joint conditions in any screening
             radiograph as determined by the central radiology reviewer.

          -  A history of osteonecrosis or osteoporotic fracture.

          -  History of significant trauma or surgery to a knee, hip or shoulder within the
             previous year.

          -  Planned surgical procedure during the duration of the study.

          -  Presence of conditions (e.g. fibromyalgia, radiculopathy) associated with moderate to
             severe pain that may confound assessments or self evaluation of osteoarthritis pain.

          -  Signs or symptoms of carpal tunnel syndrome in the year prior to Screening.

          -  Considered unfit for surgery based upon American Society of Anesthesiologists physical
             classification system for surgery grading, or subjects who would not be willing to
             undergo joint replacement surgery if required.

          -  History of intolerance or hypersensitivity to acetaminophen or any of its excipients
             or existence of a medical condition or use of concomitant medication for which the use
             of acetaminophen is contraindicated.

          -  Use of prohibited medications without the appropriate washout period prior to
             Screening or Initial Pain Assessment Period.

          -  History of cancer within 5 years of Screening, except for cutaneous basal cell or
             squamous cell cancer resolved by excision.

          -  Subjects with signs and symptoms of clinically significant cardiac disease as
             described in the protocol.

          -  Diagnosis of a transient ischemic attack in the 6 months prior to Screening, diagnosis
             of stroke with residual deficits that would preclude completion of required study
             activities.

          -  History, diagnosis, or signs and symptoms of clinically significant neurological
             disease such as but not limited to peripheral or autonomic neuropathy.

          -  History, diagnosis, signs or symptoms of any clinically significant psychiatric
             disorder.

          -  History of known alcohol, analgesic or drug abuse within 2 years of Screening.

          -  Previous exposure to exogenous NGF or to an anti-NGF antibody.

          -  History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal
             antibody or IgG fusion protein.

          -  Poorly controlled hypertension as defined in the protocol or taking an
             antihypertensive that has not been stable for at least 1 month prior to Screening.

          -  Evidence of protocol defined orthostatic hypotension at Screening.

          -  Disqualifying score on the Survey of Autonomic Symptoms questionnaire at Screening.

          -  Screening AST, ALT, serum creatinine or HbA1c values that exceed protocol defined
             limits.

          -  Presence of drugs of abuse in screening urine toxicology panel.

          -  Positive hepatitis B, hepatitis C or HIV test results indicative of current infection.

          -  Participation in other investigational drug studies within protocol defined time
             limits.

          -  Pregnant, breastfeeding or female subjects of childbearing potential who are unwilling
             or unable to follow protocol required contraceptive requirements.

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that in the judgment of the investigator, would make the subject
             inappropriate for entry into this study.