Efficacy And Safety Study Of Tanezumab Subcutaneous Administration In Osteoarthritis - A Subcutaneous/Intravenous Bridging Study

• ClinicalTrials.gov Identifier: NCT01089725
• Recruitment Status: Terminated
• First Posted: March 18, 2010
• Last Update Posted: July 3, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 11, 2010
• First Posted Date: March 18, 2010
• Last Update Posted Date: July 3, 2013
• Study Start Date: March 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 17, 2010)

• Change from Baseline to Week 16 in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) Pain subscale [ Time Frame: Baseline to 16 weeks ]
• Change from Baseline to Week 16 in the WOMAC Physical Function subscale [ Time Frame: Baseline to 16 weeks ]
• Change from Baseline to Week 16 in the Patient Global Assessment of Osteoarthritis [ Time Frame: Baseline to 16 weeks ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 17, 2010)

• WOMAC Pain subscale change from Baseline to Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, and 12 ]
• WOMAC Physical Function subscale change from Baseline to Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, and 12 ]
• Patient Global Assessment of Osteoarthritis (5-point Likert scale) change from Baseline to Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, and 12 ]
• Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) and OsteoArthritis Research Society International (OARSI) responder index at Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
• Treatment Response: Reduction in the WOMAC Pain subscale of greater than or equal to: 30%, 50%, 70%, and 90% at Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
• Cumulative distribution of percent change from Baseline in the WOMAC Pain subscale score to Weeks 1, 2, 4, 8, 12 and 16 (endpoint for summary only) [ Time Frame: Weeks 1, 2, 4, 8, 12 and 16 ]
• Treatment Response: Improvement of greater than or equal to 2 points in Patient Global Assessment of Osteoarthritis at Weeks 1, 2, 4, 8, 12, and 16 • [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
• Average pain score in the index knee change from Baseline to Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, 12, and 16 ]
• WOMAC Stiffness subscale change from Baseline to Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, 12, and 16 ]
• WOMAC Average change from Baseline to Weeks 1, 2, 4, 8, 12 and 16 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, 12 and 16 ]
• WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface, change from Baseline to Weeks 1, 2, 4, 8, 12 and 16 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, 12 and 16 ]
• WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs, change from Baseline to Weeks 1, 2, 4, 8, 12 and 16 [ Time Frame: Baseline to Weeks 1, 2, 4, 8, 12 and 16 ]
• SF-36v2TM Health Survey change from Baseline to Week 16 (8 domains plus Physical Component Summary and Mental Component Summary) [ Time Frame: Baseline to Week 16 ]
• Time to discontinuation due to Lack of Efficacy [ Time Frame: 16 weeks ]
• Incidence of patients who use rescue medication during Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
• Number of days of rescue medication use during Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
• Amount (mg) of rescue medication taken during Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
• Adverse Events [ Time Frame: 24 weeks ]
• Clinical laboratory testing (chemistry, hematology, urinalysis) [ Time Frame: 24 weeks ]
• Electrocardiogram (ECG) [ Time Frame: 24 weeks ]
• Neurologic exam (Neuropathy Impairment Score [NIS]) [ Time Frame: 24 weeks ]
• Anti Drug Antibody (ADA) assessments predose at Baseline, Week 8 and 16, and at Week 24, or Early Termination [ Time Frame: Baseline, Week 8 and 16, and at Week 24, or Early Termination ]
• Physical examinations [ Time Frame: 24 weeks ]
• Vital signs [ Time Frame: 24 weeks ]
• Injection/infusion site reactions [ Time Frame: 24 weeks ]
• Measurement of plasma tanezumab concentrations at Baseline (predose), Week 1, Week 2, Week 4, Week 8 (predose), Week 12, Week 16, and Week 24 or early termination [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8 (predose), Week 12, Week 16, and Week 24 ]
• Measurement of serum total and/or bound and/or free NGF concentrations at Baseline (predose), Week 1, Week 2, Week 4, Week 8 (predose), Week 12, Week 16 and Week 24 or early termination [ Time Frame: Baseline , Week 1, Week 2, Week 4, Week 8 (predose), Week 12, Week 16 and Week 24 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy And Safety Study Of Tanezumab Subcutaneous Administration In Osteoarthritis - A Subcutaneous/Intravenous Bridging Study
• Official Title: Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Of The Analgesic Efficacy And Safety Of Subcutaneous Administration Of Tanezumab In Patients With Osteoarthritis Of The Knee
• Brief Summary: This is an efficacy and safety study of 3 doses (2.5 mg, 5 mg and 10mg) of tanezumab administered subcutaneously versus placebo. This study will also compare a subcutaneous (SC) administration of 10 mg of tanezumab) with an intravenous (IV) administration of 10 mg of tanezumab. Each person will receive an IV infusion and a SC infusion. The study will last 16 weeks for those who wish to enter a 64-week extension study or 24 weeks for those who do not.
• Detailed Description: This study was terminated on 08 Nov 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Osteoarthritis
• Arthritis
• Pain

Intervention

• Biological: Placebo IV
  1 ml of placebo administered SC and IV once every 8 weeks.
• Biological: Placebo SC
  1 ml of placebo administered SC and IV once every 8 weeks.
• Biological: Tanezumab SC
  1 ml tanezumab injection SC administered every 8 weeks
• Biological: Placebo IV
  1 ml placebo administered IV every 8 weeks
• Biological: Placebo IV
  1ml placebo administered IV every 8 weeks
• Biological: Tanezumab IV
  1 ml tanezumab injection IV administered every 8 weeks
• Biological: Placebo SC
  1ml placebo administered SC every 8 weeks

Study Arms

• Placebo Comparator: Placebo
  Interventions:

  • Biological: Placebo IV
  • Biological: Placebo SC
• Experimental: 2.5 mg tanezumab SC and placebo IV
  Interventions:

  • Biological: Tanezumab SC
  • Biological: Placebo IV
• Experimental: 5 mg tanezumab SC and placebo IV
  Interventions:

  • Biological: Tanezumab SC
  • Biological: Placebo IV
• Experimental: 10 mg tanezumab SC and placebo IV
  Interventions:

  • Biological: Tanezumab SC
  • Biological: Placebo IV
• Experimental: 10 mg tanezumab IV
  Interventions:

  • Biological: Tanezumab IV
  • Biological: Placebo SC

• Publications *: Tive L, Bello AE, Radin D, Schnitzer TJ, Nguyen H, Brown MT, West CR. Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip. J Pain Res. 2019 Mar 19;12:975-995. doi: 10.2147/JPR.S191297. eCollection 2019. Erratum in: J Pain Res. 2020 Sep 14;13:2267-2268.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 16, 2010): 385
• Original Estimated Enrollment (submitted: March 17, 2010): 850
• Actual Study Completion Date: November 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of osteoarthritis (OA) of the knee according to American College of Rheumatology (ACR) criteria with a Kellgren- Lawrence score of greater than or equal to 2
• 18 years of age or greater
• Two methods of birth control one of which must be barrier if of childbearing potential
• Willing to discontinue pain medication except as permitted per protocol

Exclusion Criteria:

• Pregnancy or wishing to be pregnant during the course of the study, lactating women
• Body Mass Index (BMI) greater than 39
• Clinically significant cardiac, neurological, psychiatric conditions and other conditions that are excluded by the protocol.
• Previous exposure to a Nerve Growth Factor (NGF) antibody

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01089725
• Other Study ID Numbers: A4091027
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: June 2013