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Trial record 20 of 34 for:    "Osteoarthritis" | ( Map: Japan )

Study of the Analgesic Efficacy and Safety of Subcutaneous Tanezumab in Subjects With Osteoarthritis of the Hip or Knee.

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ClinicalTrials.gov Identifier: NCT02709486
Recruitment Status : Completed
First Posted : March 16, 2016
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Pfizer

Brief 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.


Condition or disease Intervention/treatment Phase
Osteoarthritis, Hip Osteoarthritis, Knee Drug: Tanezumab Drug: Placebo Phase 3

Detailed Description:

This is a randomized, double blind, placebo controlled, parallel group multicenter Phase 3 study of the efficacy and safety of tanezumab when administered by SC injection for 24 weeks compared to placebo in subjects with osteoarthritis of the knee or hip. A total of approximately 810 subjects will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (ie, 270/group). The randomization will be stratified by index joint (hip or knee), and most severe Kellgren-Lawrence grade (of any knee or hip joint) at study entry (grade 2, 3 or 4). Subjects will receive up to three SC doses of one of the following treatments at an 8-week interval between each injection:

  1. tanezumab 2.5 mg;
  2. tanezumab 5 mg;
  3. Placebo to match tanezumab. The study is designed with a total (post-randomization) duration of 48 weeks and will consist of three periods: Screening (up to 37 days), Double-blind Treatment (24 weeks) and Safety Follow-up (24 weeks). The Screening Period (beginning up to 37 days prior to Randomization) includes a Washout Period (lasting a minimum of 2 days for all prohibited pain medications), if required, and an Initial Pain Assessment Period (the 7 days prior to Randomization/Baseline).

Week 24 is the landmark analysis in this study. Subjects who do not complete the Double-blind Treatment period will enter and complete the 24-week Early-termination follow-up period.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 849 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
Actual Study Start Date : March 2, 2016
Actual Primary Completion Date : June 8, 2018
Actual Study Completion Date : November 14, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: Low dose
Investigational product
Drug: Tanezumab
2.5 mg

Experimental: High dose
Investigational product
Drug: Tanezumab
5 mg

Placebo Comparator: Placebo
Investigational product
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. WOMAC Pain subscale. [ Time Frame: 24 weeks. ]
    Change from Baseline to Week 24 in the WOMAC Pain subscale.

  2. WOMAC Physical Function subscale [ Time Frame: 24 weeks ]
    Change from Baseline to Week 24 in the WOMAC Physical Function subscale.

  3. Patient's Global Assessment of Osteoarthritis [ Time Frame: 24 weeks ]
    Change from Baseline to Week 24 in the Patient's Global Assessment of Osteoarthritis.


Secondary Outcome Measures :
  1. WOMAC Pain subscale [ Time Frame: Weeks 2, 4, 8, 12, 16, and 32. ]
    WOMAC Pain subscale change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.

  2. WOMAC Physical Function subscale [ Time Frame: Weeks 2, 4, 8, 12, 16, and 32 ]
    WOMAC Physical Function subscale change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.

  3. Patient's Global Assessment of Osteoarthritis [ Time Frame: Weeks 2, 4, 8, 12, 16, and 32. ]
    Patient's Global Assessment of Osteoarthritis (5 point Likert scale) change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.

  4. OMERACT OARSI responder index [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    OMERACT OARSI responder index at Weeks 2, 4, 8, 12, 16, 24, and 32.

  5. Cumulative distribution of percent change from Baseline in the WOMAC Pain subscale [ Time Frame: Week 16 and 24 ]
    Cumulative distribution of percent change from Baseline in the WOMAC Pain subscale score to Week 16 and 24 (endpoint for summary only).

  6. Treatment Response: Reduction in the WOMAC Pain subscale of 30%, 50%, 70% and 90% [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    Treatment Response: Reduction in the WOMAC Pain subscale of 30%, 50%, 70% and 90%, at Weeks 2, 4, 8, 12, 16, 24, and 32.

  7. Treatment Response: Reduction in the WOMAC Physical Function subscale of 30%, 50%, 70% and 90% [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    Treatment Response: Reduction in the WOMAC Physical Function subscale of 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 12, 16, 24, and 32.

  8. Cumulative distribution of percent change from Baseline in the WOMAC Physical Function subscale [ Time Frame: Week 16 and 24 ]
    Cumulative distribution of percent change from Baseline in the WOMAC Physical Function subscale score to Week 16 and 24 (endpoint for summary only).

  9. Treatment Response: Improvement of ≥2 points in Patient's Global Assessment of Osteoarthritis [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    Treatment Response: Improvement of ≥2 points in Patient's Global Assessment of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, and 32.

  10. Average pain score in the index knee or hip change [ Time Frame: Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32. ]
    Average pain score in the index knee or hip change from Baseline to Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32.

  11. WOMAC Stiffness subscale change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24 and 32 ]
    WOMAC Stiffness subscale change from Baseline to Weeks 2, 4, 8, 12, 16, 24 and 32.

  12. WOMAC Average change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    WOMAC Average score change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.

  13. WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface, change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32 ]
    WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.

  14. WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs, change from Baseline [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    WOMAC Pain Subscale Item: Pain When Going Up or Down Stairs, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.

  15. Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) impairment scores change from Baseline [ Time Frame: Weeks 8, 16 and 24. ]
    Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) impairment scores change from Baseline to Weeks 8, 16 and 24.

  16. EQ 5D-5L Health State Utility and Five Items [ Time Frame: Weeks 8, 16 and 24. ]
    EQ 5D-5L Health State Utility and Five Items (Mobility; Self-Care; Usual Activities; Pain/Discomfort; Anxiety/Depression) change from Baseline to Weeks 8, 16 and 24.

  17. Patient Reported Treatment Impact Assessment-Modified (mPRTI) [ Time Frame: Weeks 16 and 24. ]
    Patient Reported Treatment Impact Assessment-Modified (mPRTI) at Weeks 16 and 24.

  18. Health Care Resource Utilization [ Time Frame: Weeks 32 and 48. ]
    Health Care Resource Utilization at Baseline, and Weeks 32 and 48.

  19. Incidence of discontinuation due to Lack of Efficacy [ Time Frame: 24 weeks ]
    Incidence of discontinuation due to Lack of Efficacy.

  20. Incidence of rescue medication use [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, and 32. ]
    Usage of rescue medication (incidence and number of days of use) during Weeks 2, 4, 8, 12, 16, 24, and 32.

  21. Amount of rescue medication taken [ Time Frame: Weeks 2, 4, 8, 12, 16 and 24. ]
    Usage of rescue medication (amount taken) during Weeks 2, 4, 8, 12, 16 and 24.

  22. Incidence of Subjects with Adverse Events. [ Time Frame: 48 weeks ]
    Adverse Events.

  23. Hematology testing [ Time Frame: Weeks 16 and 32. ]
    Hematology testing

  24. Blood pressure [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Blood pressure in mmHg

  25. Electrocardiogram [ Time Frame: Weeks 24 and 48. ]
    Electrocardiogram

  26. Incidence of individual adjudication outcomes [ Time Frame: 48 weeks ]
    The Adjudication Committee will be asked to review all possible or probable joint related safety events, total joint replacement, as well as investigator reported adverse events of osteonecrosis, rapidly progressive osteoarthritis, subchondral insufficiency fracture (spontaneous osteonecrosis of the knee [SPONK]) or pathologic fracture.

  27. Incidence of all cause total joint replacements [ Time Frame: 48 weeks ]
    All cause total joint replacement as defined in the protocol.

  28. Orthostatic (supine / standing) blood pressure assessments. [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Orthostatic (supine / standing) blood pressure assessments.

  29. Survey of Autonomic Symptom scores. [ Time Frame: Week 24. ]
    Survey of Autonomic Symptom scores.

  30. Neurologic exam (Neuropathy Impairment Score [NIS]). [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32,and 48. ]
    Neurologic exam (Neuropathy Impairment Score [NIS]).

  31. Anti-tanezumab antibody assessments. [ Time Frame: Weeks 8, 16, 24, 32 and 48. ]
    Anti-tanezumab antibody assessments.

  32. Musculoskeletal examination. [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Physical examination of all major joints.

  33. Time to discontinuation due to Lack of Efficacy. [ Time Frame: 24 weeks ]
    Time to discontinuation due to Lack of Efficacy.

  34. Clinical chemistry testing [ Time Frame: Weeks 16 and 32. ]
    Clinical chemistry testing

  35. General examination [ Time Frame: Week 24 ]
    General examination including cardiovascular, respiratory, abdominal and skin systems.

  36. Heart rate [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32 and 48. ]
    Heart rate in beats per minutes



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02709486


  Show 148 Study Locations
Sponsors and Collaborators
Pfizer
Eli Lilly and Company
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02709486     History of Changes
Other Study ID Numbers: A4091057
2013-004508-21 ( EudraCT Number )
OA 6-MONTH EU STUDY ( Other Identifier: Alias Study Number )
First Posted: March 16, 2016    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
Osteoarthritis, pain, tanezumab.

Additional relevant MeSH terms:
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Osteoarthritis
Osteoarthritis, Knee
Osteoarthritis, Hip
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Analgesics
Tanezumab
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs