Phase 3
Completed N=698
Efficacy and Safety of a Subcutaneous Tanezumab Titration Dosing Regimen in Subjects With Moderate to Severe Osteoarthritis of the Hip or Knee
Osteoarthritis, Knee · Osteoarthritis, Hip
Source: ClinicalTrials.gov NCT02697773 ↗
Enrolled (actual)
698
Serious AEs
3.9%
Results posted
Apr 2019
Primary outcomePrimary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 — -2.64; -3.23; -3.37 units on a scale — p=0.0129
◆ Published Evidence
Established
27citations · ~9 / year
Characterization of adverse joint outcomes in patients with osteoarthritis treated with subcutaneous tanezumab.
Summary
The primary purpose of this study is to evaluate the efficacy of a titration arm of tanezumab in which treatment is started at a lower dose (2.5 mg) and increased to a higher dose (5 mg) at Week 8, compared to giving 2 doses of tanezumab 2.5 mg or 2 doses of placebo. The study also evaluates the safety of the treatment regimens.
Linked Publications (5)
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Characterization of adverse joint outcomes in patients with osteoarthritis treated with subcutaneous tanezumab.
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Meaningful within-patient change for clinical outcome assessments: model-based approach versus cumulative distribution functions.
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Inter-Reader Consistency and Exclusionary Findings During Radiographic Screening for Phase 3 Trials of Tanezumab in Patients With Osteoarthritis.
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Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis.
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Prediction of relative change in free nerve growth factor following subcutaneous administration of tanezumab, a novel monoclonal antibody to nerve growth factor.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 |
-2.64; -3.23; -3.37 | 0.0129 sig |
| PRIMARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16 |
-2.56; -3.22; -3.45 | 0.0065 sig |
| PRIMARY Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16 |
-0.65; -0.87; -0.90 | 0.0109 sig |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8 and 12 |
-2.20; -2.87; -2.89; -2.40; -3.28; -3.27 | 0.0020 sig |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24 |
7.30; 7.08; 7.33; -3.07; -2.80; -2.95 | — |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8 and 12 |
-2.14; -2.89; -3.05; -2.28; -3.30; -3.38 | 0.0004 sig |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24 |
7.38; 7.18; 7.39; -3.03; -2.85; -3.01 | — |
| SECONDARY Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8 and 12 |
-0.74; -0.91; -0.87; -0.75; -1.01; -0.97 | 0.0236 sig |
| SECONDARY Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 24 |
3.46; 3.42; 3.53; -0.87; -0.72; -0.91 | — |
| SECONDARY Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index |
50.4; 65.4; 67.4; 58.6; 74.0; 74.7 | 0.0027 sig |
| SECONDARY Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >= 30 Percent (%), >=50%, >=70% and >=90% Response |
38.8; 56.3; 56.2; 22.8; 38.5; 38.2 | 0.0009 sig |
| SECONDARY Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 |
82.3; 87.4; 88.4; 79.3; 81.8; 85.4 | — |
| SECONDARY Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >= 30 Percent (%), >=50%, >=70% and >=90% Response |
35.8; 55.8; 56.7; 23.7; 35.1; 39.9 | 0.0001 sig |
| SECONDARY Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16 |
83.6; 89.2; 90.6; 75.4; 81.0; 83.3 | — |
| SECONDARY Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis |
19.8; 25.1; 22.3; 20.7; 27.7; 27.5 | 0.1463 |
| SECONDARY Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12 and 16 |
-1.27; -1.60; -1.65; -1.68; -2.32; -2.23 | 0.0319 sig |
| SECONDARY Change From Baseline for Average Pain Score in the Index Joint at Weeks 20 and 24 |
7.27; 6.89; 7.13; -2.58; -2.76; -3.26 | — |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12 and 16 |
-1.85; -2.90; -2.90; -2.04; -3.28; -3.27 | <.0001 sig |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 24 |
7.49; 7.27; 7.58; -2.77; -2.74; -2.86 | — |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12 and 16 |
-2.07; -2.88; -2.95; -2.24; -3.28; -3.31 | <.0001 sig |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 24 |
7.39; 7.18; 7.44; -2.96; -2.80; -2.94 | — |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Weeks 2, 4, 8, 12 and 16 |
-2.09; -2.75; -2.76; -2.31; -3.16; -3.22 | 0.0026 sig |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 24 |
7.22; 7.03; 7.24; -2.93; -2.64; -2.74 | — |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (Pain When Going up or Down Stairs) at Weeks 2, 4, 8, 12 and 16 |
-2.24; -2.88; -3.10; -2.53; -3.50; -3.63 | 0.0058 sig |
| SECONDARY Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (Pain When Going up or Down Stairs) at Week 24 |
8.09; 7.91; 8.13; -3.12; -2.76; -2.86 | — |
| SECONDARY Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline |
4.6; 7.4; 8.4; 60.9; 59.5; 60.1 | — |
| SECONDARY Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Week 16 |
-3.58; -2.97; -5.26; -21.89; -27.32; -27.48 | 0.6984 |
| SECONDARY European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Dimensions Score |
3.0; 3.0; 3.0; 2.2; 2.3; 2.3 | — |
| SECONDARY European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score/Index Value |
0.63; 0.63; 0.61; 0.75; 0.77; 0.76 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis |
1.0; 1.0; 1.0; 1.0; 2.0; 1.0 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Osteoarthritis |
1; 2; 4; 0; 0; 2 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis |
1.0; 2.0; 1.0; 2.5; 1.0; 1.0 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Osteoarthritis |
0; 0; 0; 2; 0; 2 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis |
3.0; 2.0; 3.5; 1.5 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things |
196; 187; 189; 2; 5; 10 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Osteoarthritis |
7; 9; 11; 2; 1; 5 | — |
| SECONDARY Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis |
4.3; 2.2; 4.3; 0.9; 5.0; 1.3 | — |
| SECONDARY Number of Participants Who Withdrew Due to Lack of Efficacy |
13; 6; 4 | 0.1444 |
| SECONDARY Time to Discontinuation Due to Lack of Efficacy |
NA; NA; NA | 0.0809 |
| SECONDARY Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12 and 16 |
160; 137; 138; 143; 119; 110 | 0.0761 |
| SECONDARY Number of Participants Who Took Rescue Medication During Week 24 |
108; 125; 118 | — |
| SECONDARY Number of Days of Rescue Medication Use at Week 2, 4, 8, 12 and 16 |
2.46; 2.27; 2.02; 2.20; 1.93; 1.68 | 0.4833 |
| SECONDARY Number of Days of Rescue Medication Use at Week 24 |
1.3; 2.0; 1.8 | — |
| SECONDARY Amount of Rescue Medication Taken at Weeks 2, 4, 8, 12 and 16 |
3226.0; 3139.1; 2537.6; 3033.2; 2815.6; 2005.3 | 0.9164 |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
145; 156; 143; 9; 7; 11 | — |
| SECONDARY Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) |
31; 40; 33; 0; 0; 0 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline |
20; 12; 11 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline |
14; 10; 3 | — |
| SECONDARY Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 40 |
126.6; 126.4; 127.3; -0.7; -1.8; -0.8 | — |
| SECONDARY Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12,16, 24, 40 |
70.9; 71.4; 72.5; 0.7; 1.1; 0.3 | — |
| SECONDARY Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16 and 40 |
932.4; 927.3; 911.0; -20.4; -13.1; -10.1 | — |
| SECONDARY Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 16 and 40 |
65.8; 66.3; 67.2; 1.3; 0.9; 0.8 | — |
| SECONDARY Percentage of Participants With Adjudicated Joint Safety Outcomes |
0; 2.2; 0.4; 0; 2.2; 0.4 | — |
| SECONDARY Percentage of Participants With Total Joint Replacements |
1.7; 3.5; 6.9 | — |
| SECONDARY Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8,12,16, 24 and 40 |
1.09; 2.01; 1.80; -0.21; -0.14; -0.31 | — |
| SECONDARY Number of Participants With Confirmed Orthostatic Hypotension |
1; 3; 1 | — |
| SECONDARY Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Weeks 24 and 40 |
0.47; 0.54; 0.45; 0.42; 0.30; 0.38 | — |
| SECONDARY Number of Participants With Anti-Tanezumab Antibodies |
25; 25; 23; 22; 29; 36 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of Osteoarthritis of the knee or hip confirmed by X-ray
- Documented history that subject tried the following medications and had insufficient pain relief or is cannot take or tolerate them: acetaminophen, NSAIDs and either tramadol or opioids
- Meet the protocol requirements for pain at screening and pain, physical function and patient global assessment of osteoarthritis at baseline
- Willing to discontinue all pain medications except study medication and rescue medication during the course of the study and use those as directed per protocol
- Women able to have children must agree to use 2 forms of contraception during the study
Exclusion Criteria
- Body Mass Index (BMI) greater than 39
- History of diseases other than osteoarthritis in a shoulder, hip or knee (example, rheumatoid arthritis, gout, joint infections, osteonecrosis)
- Patients with x-ray showing joint conditions such as osteonecrosis (dead bone) or certain types of fractures
- Patients who have had significant trauma or surgery to a knee, hip or shoulder within the previous year
- Planned surgical procedure during the study
- Patients who are largely or wholly incapacitated (example bedridden or confined to a wheelchair, permitting little or no self-care)
- Patients who would be unwilling or unable to undergo joint replacement surgery if one eventually became necessary
- Patients with significant conditions other than osteoarthritis that could interfere with assessment of pain in the joints (example fibromyalgia, lupus erythematosus)
- Patients with significant heart, neurological or psychiatric diseases
- Patients who had cancer other than certain skin cancers within the past 5 years
- Patients with alcohol, analgesic (pain medications) or drug abuse within the past 2 years
- Women who are pregnant, breast-feeding or intending to become pregnant or breast-feed during the course of the study.
Data sourced from ClinicalTrials.gov (NCT02697773) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.