Long Term Safety and Efficacy Study of Tanezumab in Japanese Adult Subjects With Chronic Low Back Pain
Condition: Low Back Pain
MeSH terms: Back Pain; Low Back Pain
Intervention: Celecoxib; Tanezumab 5 mg; Tanezumab 10 mg; Placebo for celecoxib; Placebo for tanezumab
Intervention description: Orally administered Celecoxib 100 mg twice daily for 56 weeks; Subcutaneous injection of tanezumab 5 mg every 8 weeks for 56 weeks; Subcutaneous injection of tanezumab 10 mg every 8 weeks for 56 weeks; Orally administered the placebo twice daily for 56 weeks; Subcutaneous injection of the placebo every 8 weeks for 56 weeks
Intervention MeSH terms: Celecoxib; Tanezumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 277.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic low back pain; Chronic pain

Summary:

      This study will investigate the long-term safety and efficacy of a fixed dose of tanezumab 5
      mg and 10 mg administered subcutaneously (SC) seven times at 8 week intervals. The primary
      objective of this study is to evaluate the long term safety of tanezumab 5 mg and 10 mg
      administrated SC every 8 weeks (7 administrations). In addition, the study will evaluate the
      long term analgesic efficacy of tanezumab 5 mg and 10 mg SC administered every 8 weeks (7
      administrations).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Duration of chronic low back pain for ≥3 months, and treatment with agents for low
             back pain for ≥3 months.

          -  Primary location of low back pain must be between the 12th thoracic vertebra and the
             lower gluteal folds, with or without radiation into the posterior thigh, classified as
             Category 1 or 2 according to the classification of the Quebec Task Force in Spinal
             Disorders.

          -  Subjects must be experiencing some benefits from their current stable dose regimen of
             oral NSAID (celecoxib, loxoprofen or meloxicam) treatment as described in the
             protocol, be tolerating their NSAID regimen, be taking this medication regularly
             during the 30 day period prior to the Screening visit and must have had some
             improvement in low back pain, but still require additional pain relief at Screening.

          -  Subjects must maintain a stabilized, protocol specified NSAID dose regimen for at
             least the final 2 or 3 weeks of the Screening period.

          -  Low Back Pain Intensity (LBPI) score of ≥5 at Screening.

          -  Subjects must be willing to discontinue all pain medications for chronic low back pain
             except rescue medication and investigational product and not use prohibited pain
             medications throughout the duration of the study.

          -  Female subjects of childbearing potential and at risk for pregnancy must agree to
             comply with protocol specified contraceptive requirements.

        Exclusion Criteria:

          -  Subjects exceeding protocol defined BMI limits.

          -  Diagnosis of osteoarthritis of the knee or hip as defined by the ACR combined clinical
             and radiographic 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.

               -  Subjects who have Kellgren Lawrence Grade < or =2 radiographic evidence of knee
                  osteoarthritis but who do not meet ACR criteria and do not have pain associated
                  with their knee osteoarthritis will be allowed.

          -  Subjects with symptoms and radiologic findings consistent with osteoarthritis in the
             shoulder.

          -  History of lumbosacral radiculopathy within the past 2 years, history of spinal
             stenosis associated with neurological impairment, or history of neurogenic
             claudication.

          -  Back pain due to recent major trauma within 6 months prior to Screening.

          -  Surgical intervention during the past 6 months for the treatment of low back pain.

          -  Planned surgical procedure during the duration of the study.

          -  History or radiographic evidence of other diseases that could confound efficacy or
             safety assessments (eg, 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.

          -  History of osteonecrosis or osteoporotic fracture.

          -  History of significant trauma or surgery to a knee, hip, or shoulder within the
             previous year.

          -  Signs or symptoms of carpal tunnel syndrome in the one 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 celecoxib/acetaminophen or any of its
             excipients or existence of a medical condition or use of concomitant medication for
             which the use of celecoxib/acetaminophen is contraindicated.

          -  Use of prohibited medications or prohibited non-pharmacological treatments without the
             appropriate washout period (if applicable) prior to Screening or IPAP.

          -  History of known alcohol, analgesic or narcotic abuse within 2 years of Screening.

          -  Presence of drugs of abuse or illegal drugs in the urine toxicology screen obtained at
             Screening.

          -  History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal
             antibody or IgG-fusion protein.

          -  Signs and symptoms of clinically significant cardiac disease.

          -  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.

          -  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 of cancer within 5 years prior to Screening, except for cutaneous basal cell
             or squamous cell cancer resolved by excision.

          -  Expected to undergo a therapeutic procedure or to use any analgesic other than those
             specified in the protocol throughout the pre-treatment and treatment periods that is
             likely to confound assessment of analgesic efficacy or safety.

          -  Previous exposure to exogenous NGF or to an anti-NGF antibody.

          -  Screening AST, ALT, serum creatinine or HbA1c values that exceed protocol defined
             limits.

          -  Positive Hepatitis B, Hepatitis C, or HIV tests at screening indicative of current
             infection.

          -  History, diagnosis, or signs and symptoms of clinically significant neurological
             disease or clinically significant psychiatric disorder.

          -  Pregnant, breastfeeding or female subjects of childbearing potential who are unwilling
             or unable to follow protocol required contraceptive requirements.

          -  Participation in other investigational drug studies within protocol defined time
             limits.

          -  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.