Clinical Trials List
Protocol NumberA4091058
2016-03-15 - 2019-03-15
Phase III
Terminated5
ICD-10M17.9
Osteoarthritis of knee, unspecified
ICD-10M16.9
Osteoarthritis of hip, unspecified
ICD-9715.35
Osteoarthrosis, localized, not specified whether primary or secondary, pelvic region and thigh
A PHASE 3 RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, MULTICENTER STUDY OF THE LONG-TERM SAFETY AND EFFICACY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
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Trial Applicant
Syneos Health
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Wen Chan Tsai 風濕免疫科
- Sung Wan-Yu 風濕免疫科
- 歐燦騰 風濕免疫科
- 吳正欽 風濕免疫科
- Chia-Chun Tseng 風濕免疫科
- Hsuan-Ti Huang 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 洪偉哲 風濕免疫科
- Po-Hao Huang 風濕免疫科
- 張詩欣 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
OSTEOARTHRITIS OF THE HIP OR KNEE
Objectives
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.
Test Drug
Tanezumab (PF-04383119 )
Active Ingredient
Tanezumab
Dosage Form
injection
Dosage
2.5
5
5
Endpoints
Primary Outcome Measures :
Percentage of Participants With Adjudicated Primary Composite Joint Safety Outcome [ Time Frame: Baseline up to Week 80 ]
Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive osteoarthritis (OA) type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of joint space width (JSW) (greater than or equal to [>=] 2 millimeters [mm]) within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Observation Time-Adjusted Event Rate of Participants With Adjudicated Primary Composite Joint Safety Outcome [ Time Frame: Baseline up to Week 80 ]
Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Primary joint safety outcome included participants with adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 [ Time Frame: Baseline, Week 16 ]
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions, which may not be a whole (integer) number, scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16 [ Time Frame: Baseline, Week 16 ]
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16 [ Time Frame: Baseline, Week 16 ]
PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using Interactive Response Technology (IRT), where 1=very good (no symptom 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 and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Percentage of Participants With Adjudicated Primary Composite Joint Safety Outcome [ Time Frame: Baseline up to Week 80 ]
Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive osteoarthritis (OA) type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of joint space width (JSW) (greater than or equal to [>=] 2 millimeters [mm]) within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Observation Time-Adjusted Event Rate of Participants With Adjudicated Primary Composite Joint Safety Outcome [ Time Frame: Baseline up to Week 80 ]
Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Primary joint safety outcome included participants with adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 [ Time Frame: Baseline, Week 16 ]
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions, which may not be a whole (integer) number, scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16 [ Time Frame: Baseline, Week 16 ]
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16 [ Time Frame: Baseline, Week 16 ]
PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using Interactive Response Technology (IRT), where 1=very good (no symptom 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 and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Inclution 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 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
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
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
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
The Estimated Number of Participants
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Taiwan
80 participants
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Global
3000 participants
