Long Term Safety and Efficacy Study of Tanezumab in Subjects With Osteoarthritis of the Hip or Knee

Pfizer

Status and phase: Completed; Phase 3

Conditions: Osteoarthritis, Hip; Chronic Pain; Osteoarthritis, Knee

Treatments: Drug: NSAID; Biological: Tanezumab 2.5 mg; Biological: Tanezumab 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02528188

OA SAFETY STUDY (Other Identifier)

2012-003721-22 (EudraCT Number)

A4091058

Details and patient eligibility

About

The purpose of this study is to compare the long-term joint safety and efficacy (pain relief) of the investigational study drug, tanezumab compared to non-steroidal anti inflammatory drugs (NSAIDs) in subjects with osteoarthritis of the hips or knees.

Enrollment: 3,021 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 2 as diagnosed by the Central Reader
• Currently receiving a stable dose regimen of oral NSAID (naproxen, celecoxib, diclofenac, aceclofenac, loxoprofen, ibuprofen, meloxicam, nabumetone, sulindac or ketoprofen) as described in the protocol along with a history of insufficient pain relief from, inability to tolerate or contraindication to taking acetaminophen and, tramadol or opioid treatments. Subjects must also maintain a stabilized, protocol specified NSAID dose regimen for at least the final 2 or 3 weeks of the Screening period
• WOMAC Pain subscale score of at least 5 in the index knee or hip 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 (eg, 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 (eg, fibromyaliga, 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
• Contraindications to magnetic resonance imaging
• History of intolerance or hypersensitivity to the oral NSAID (naproxen, celecoxib or diclofenac) the subject could be randomized to receive or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of this NSAID is contraindicated
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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3,021 participants in 3 patient groups

NSAID

Active Comparator group

Description:

Subcutaneous injection of placebo for tanezumab every 8 weeks plus oral NSAID (naproxen 500 mg, celecoxib 100 mg or diclofenac 75 mg) twice daily for 56 weeks

Treatment:

Drug: NSAID

Tanezumab 2.5 mg

Experimental group

Description:

Subcutaneous injection of tanezumab 2.5 mg every 8 weeks plus oral placebo for NSAID (naproxen, celecoxib or diclofenac ER) twice daily for 56 weeks

Treatment:

Biological: Tanezumab 2.5 mg

Tanezumab 5 mg

Experimental group

Description:

Subcutaneous injection of tanezumab 5 mg every 8 weeks plus oral placebo for NSAID (naproxen, celecoxib or diclofenac) twice daily for 56 weeks

Treatment:

Biological: Tanezumab 5 mg