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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01089725
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : March 18, 2010
Results First Posted : May 5, 2021
Last Update Posted : May 5, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Osteoarthritis Arthritis Pain Biological: Placebo IV Biological: Placebo SC Biological: Tanezumab SC Biological: Tanezumab IV Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 385 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 SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE.
Actual Study Start Date : March 30, 2010
Actual Primary Completion Date : November 8, 2010
Actual Study Completion Date : February 18, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Placebo Comparator: Placebo 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.

Experimental: 2.5 mg tanezumab SC and placebo IV Biological: Tanezumab SC
1 ml tanezumab injection SC administered every 8 weeks

Biological: Placebo IV
1 ml placebo administered IV every 8 weeks

Experimental: 5 mg tanezumab SC and placebo IV Biological: Tanezumab SC
1 ml tanezumab injection SC administered every 8 weeks

Biological: Placebo IV
1ml placebo administered IV every 8 weeks

Experimental: 10 mg tanezumab SC and placebo IV Biological: Tanezumab SC
1 ml tanezumab injection SC administered every 8 weeks

Biological: Placebo IV
1ml placebo administered IV every 8 weeks

Experimental: 10 mg tanezumab IV Biological: Tanezumab IV
1 ml tanezumab injection IV administered every 8 weeks

Biological: Placebo SC
1ml placebo administered SC every 8 weeks




Primary Outcome Measures :
  1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 [ Time Frame: Baseline, Week 16 ]
    The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.

  2. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16 [ Time Frame: Baseline, Week 16 ]
    The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on a NRS of 0 to 10, where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function.

  3. Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis Score at Week 16 [ Time Frame: Baseline, Week 16 ]
    Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by using a 5-point scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities) and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated severe condition.


Secondary Outcome Measures :
  1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]
    The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.

  2. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]
    The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on a NRS of 0 to 10, where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function.

  3. Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]
    Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by using a 5-point scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities) and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated severe condition.

  4. Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
    The OMERACT-OARSI responder index is based on 3 parameters. OMERACT-OARSI response: greater than or equal to (>=) 50 percent (%) improvement from baseline and absolute change from baseline of >=2 units at week of interest in WOMAC pain or physical function subscale, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score range: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score range: 0-10, higher score=higher pain/difficulty).

  5. Percentage of Participants With at Least 30%, 50%, 70% and 90% Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
    The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain.

  6. Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score at Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Weeks 1, 2, 4, 8, 12, 16 ]
    The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. Participants with specified reduction (as percent) from baseline at Week 16 are reported.

  7. Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
    Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by using a 5-point scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities) and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated severe condition. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value.

  8. Change From Baseline in Average Pain Score in the Index Knee at Weeks 1, 2, 4, 8, 12 and 16 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, and 16 ]
    Participants assessed average osteoarthritis pain in their knee in the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Higher score indicated greater pain. Baseline score was calculated as the mean of the scores over the 3 days in the initial pain assessment period and a weekly mean was calculated using the daily pain scores within each study week.

  9. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, and 16 ]
    The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 2 individual questions scored on NRS of 0 to 10, with higher scores indicating more stiffness. Total score range for WOMAC stiffness subscale score is 0 to 10, where higher scores indicate more stiffness. Stiffness is defined as a sensation of decreased ease in movement of the knee.

  10. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, and 16 ]
    WOMAC: self-administered, disease-specific 24-item questionnaire, which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items) and physical function (17 items) in participants with osteoarthritis of knee. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores. WOMAC pain, physical function and stiffness subscale and average score ranges from 0 to 10, where higher score indicates worse response.

  11. Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, and 16 ]
    Participants answered: "How much pain have you had when walking on a flat surface?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. Higher score indicated greater pain.

  12. Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 1, 2, 4, 8, 12, and 16 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, and 16 ]
    Participants answered: "How much pain have you had when going up or down stairs?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. Higher score indicated greater pain.

  13. Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 16 [ Time Frame: Baseline, Week 16 ]
    SF-36v2 is a standardized self-administered survey evaluating 8 aspects/domains of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The total score for each domain is scaled 0-100 (100 = highest level of functioning).

  14. Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 16 [ Time Frame: Baseline, Week 16 ]
    SF-36v2: standardized self-administered survey evaluating 8 aspects of functional health and wellbeing (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each aspect were scaled 0-100 (100=highest level of functioning). For obtaining physical and mental component scores, z-score for each scale=(observed score - mean score for general 1990 United States [US] population)/corresponding standard deviation. The 2 component scores were obtained by multiplying each aspect z-score by physical or mental factor score coefficient (1990 general US population) and summing the eight products. Component scores indicated how many standard deviations higher (in case of positive z-score [better functioning])/lower (in case of negative z-score [worse functioning]) participant's value was relative to the mean of the reference population.

  15. Time to Discontinuation Due to Lack of Efficacy [ Time Frame: Baseline up to Week 24 ]
    Median time to discontinuation due to lack of efficacy for participants who discontinued due to lack of efficacy was reported.

  16. Percentage of Participants Who Used Rescue Medication [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
    In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Incidence of rescue medication use is calculated as any use of rescue medication during the study week in question.

  17. Duration of Rescue Medication Use [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
    In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Duration of rescue medication use is calculated as the number of study days per week when any rescue medication was taken.

  18. Amount of Rescue Medication Taken [ Time Frame: Weeks 1, 2, 4, 8, 12, and 16 ]
    In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. The amount of rescue medication taken is the total dose (in mg) of acetaminophen rescue medication over the study week in question.


Other Outcome Measures:
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 112 days after last dose of study treatment ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  2. Number of Participants With Abnormal Laboratory Findings [ Time Frame: Day 1 up to Week 24 ]
    Laboratory examination included blood chemistry, hematology and urinalysis. Reported results include abnormal laboratory findings without regard to baseline abnormality.

  3. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [ Time Frame: Baseline up to Week 24 ]
    Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's formula (QTcF), QT interval corrected using the Bazett's formula (QTcB), RR interval and heart rate (HR). Number of participants with clinically significant abnormal ECG findings reported as adverse events were presented.

  4. Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, and 24 ]
    The NIS constitutes the sum of 37 standard items of neuromuscular examination used to assess the muscle strength, reflexes and sensation. Each item is scored separately for left and right sides. Components of muscle weakness (24 items) are scored on a scale from 0 (normal) to 4 (paralysis), with higher score = more weakness; components of reflexes and sensation (13 items) scored on a scale with 0 = normal, 1 = decreased or 2 = absent. Total NIS score range 0-244 with higher score = more impairment.

  5. Number of Participants With Anti-drug Antibodies (ADA) [ Time Frame: Baseline, Weeks 8, 16, 24 or Early Termination ]
    Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA). Same participant may have positive ADA result at more than 1 time point.

  6. Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Baseline up to Week 24 ]
    Physical examination included examination of following sites in addition to general examination: abdomen, ears, extremities, eyes, head, heart, musculoskeletal, neck, nose, skin, throat, lungs and thyroid.

  7. Number of Participants With Clinically Significant Abnormality in Vital Signs [ Time Frame: Baseline to Week 24 ]
    Following parameters were analyzed for examination of vital signs: body temperature, blood pressure, pulse rate and respiratory rate. Number of participants with clinically significant abnormality in vital signs reported as adverse events were presented.

  8. Number of Participants With Injection and Infusion Site Reactions [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, and 24 ]
    The injection and infusion site reactions were assessed based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after administration of subcutaneous injection or intravenous infusion.

  9. Plasma Tanezumab Concentration [ Time Frame: Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, 24 or End of treatment ]
  10. Total and Free Nerve Growth Factor (NGF) Concentration [ Time Frame: Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, and 24 or End of treatment ]
    Serum samples were analyzed for determining total and free (unbound) NGF concentration. Total NGF was analyzed using a validated, sensitive and specific immunoaffinity enrichment liquid chromatography tandem mass spectrometric (IA/LC/MS/MS) method and free (unbound) NGF was analyzed using a validated, sensitive, and specific electrochemiluminescence (ECL) ligand binding assay.

  11. Number of Participants With Intravenous or Subcutaneous Doses of Study Medication [ Time Frame: Baseline up to Week 8 ]
    Number of participants were reported based on the maximum number of intravenous or subcutaneous doses of either tanezumab or placebo received.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT01089725


Locations
Show Show 91 study locations
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01089725    
Other Study ID Numbers: A4091027
SC/IV OA STUDY ( Other Identifier: Alias Study Number )
First Posted: March 18, 2010    Key Record Dates
Results First Posted: May 5, 2021
Last Update Posted: May 5, 2021
Last Verified: February 2021
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
Keywords provided by Pfizer:
safety
efficacy
parallel group
double-blind
multicenter
injection
infusion
osteoarthritis
bridging
subcutaneous
intravenous
tanezumab
Additional relevant MeSH terms:
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Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Tanezumab
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs