E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoarthritis of the hip or knee |
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E.1.1.1 | Medical condition in easily understood language |
Osteoarthritis of the hip or knee |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020108 |
E.1.2 | Term | Hips osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Demonstrate superior efficacy of tanezumab 5 mg and 2.5 mg administered subcutaneously (SC) every 8 weeks versus placebo at Week 24. |
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E.2.2 | Secondary objectives of the trial |
•Evaluate the safety of tanezumab 2.5 mg SC and 5 mg SC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. - Male or female ≥18 years of age. - A diagnosis of osteoarthritis of the hip or knee in the index joint based on American College of Rheumatology criteria with x-ray confirmation (a Kellgren-Lawrence 17 x-ray grade of ≥2 as diagnosed by the Central Reader). - Acetaminophen and oral NSAID therapy do not provide adequate pain relief, or subject is unable to take NSAID; tramadol treatment has not provided adequate pain relief or subject is unable to take tramadol; opioid treatment has not provided adequate pain relief or subject is unwilling to take opioids, or unable to take opioids. - WOMAC Pain subscale Numerical Rating Scale (NRS) ≥5 in the index joint at Screening. - Subjects must be willing to discontinue all pain medications for osteoarthritis except rescue medication (acetaminophen) and not use prohibited pain medications throughout the duration of the study except as permitted per protocol. - Female subjects of childbearing potential and at risk for pregnancy must agree to use 2 highly effective or acceptable methods of contraception throughout the study and for 112 days (16 weeks) after the last dose of assigned subcutaneous investigational product. - Female subjects who are not of childbearing potential meet at least one of the following criteria: •Have undergone a documented hysterectomy and/or bilateral oophorectomy; •Have medically confirmed ovarian failure; or •Achieved post-menopausal status defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle stimulating hormone (FSH) level confirming the post-menopausal state. - Subjects who are willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures through the End of Study visit. |
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E.4 | Principal exclusion criteria |
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial. - Body Mass Index (BMI) of >39 kg/m2. History or radiographic evidence of other diseases that could confound efficacy assessments (e.g., rheumatoid arthritis). History or radiographic evidence of orthopedic conditions that may increase the risk of, or confound assessment of joint safety conditions during the study. - Planned surgical procedure during the duration of the study. - Largely or wholly incapacitated, (eg, subject bedridden or confined to a wheelchair, permitting little or no self-care). - Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with osteoarthritis. Subjects with a present (current) history of sciatica are not eligible for participation. Subjects with a past history of sciatica who have been asymptomatic for at least one year and who have no evidence of radiculopathy or sciatic neuropathy on thorough neurologic examination are eligible for participation. - Subjects with a past history of carpal tunnel syndrome (CTS) with signs or symptoms of CTS in the one year prior to Screening. - Subjects considered unfit for surgery, defined as Grade >3 on the American Society of Anesthesiologists (ASA) physical classification system for surgery, or subjects who would not be willing to undergo joint replacement surgery if required. - History of intolerance or hypersensitivity to acetaminophen (paracetamol) or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of acetaminophen is contraindicated (refer to product labeling). - Use of prohibited medications without the appropriate washout period (if applicable) prior to Screening or Initial Pain Assessment Period. - Oral or intramuscular corticosteroids within 30 days prior to the Initial Pain Assessment Period. - Intra-articular corticosteroid injection in the index joint within 12 weeks, or to any other joint within 30 days prior to the Initial Pain Assessment Period. - Intra-articular hyaluronic acid injection in the index joint within 30 days (or within 18 weeks for long-acting formulations such as Synvisc) prior to the Initial Pain Assessment Period. - History of cancer within 5 years prior to Screening, except for cutaneous basal cell or squamous cell cancer resolved by excision. See the protocol for additional Exclusion Criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary efficacy endpoints are: •Change from Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Pain subscale; •Change from Baseline to Week 24 in the WOMAC Physical Function subscale; •Change from Baseline to Week 24 in the Patient’s Global Assessment of Osteoarthritis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints are listed with the Endpoints. |
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E.5.2 | Secondary end point(s) |
Efficacy Measures •WOMAC Pain subscale change from Baseline to Weeks 2, 4, 8, 12, 16, and 32. •WOMAC Physical Function subscale change from Baseline to 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. •Outcome Measures in Rheumatology – Osteoarthritis Research Society Initiative (OMERACT-OARSI) responder index at Weeks 2, 4, 8, 12, 16, 24, and 32. •Cumulative distribution of percent change from Baseline in the WOMAC Pain subscale score to Week 16 and 24 (endpoint for summary only). •Treatment Response: Reduction in the WOMAC Pain subscale of ≥30%, ≥50%, ≥70% and ≥90%, at 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. •Cumulative distribution of percent change from Baseline in the WOMAC Physical Function subscale score to Week 16 and 24 (endpoint for summary only). •Treatment Response: Improvement of ≥2 points in Patient’s Global Assessment of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, 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. •WOMAC Stiffness subscale change from Baseline to 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. •WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32. •WOMAC Pain Subscale Item: Pain When Going Up or Downstairs, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32. •Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) impairment scores change from Baseline to 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. •Patient Reported Treatment Impact Assessment-Modified (mPRTI) at Weeks 16 and 24. •Health Care Resource Utilization at Baseline, and Weeks 32 and 48. •Incidence and time to discontinuation due to Lack of Efficacy. •Usage of rescue medication (incidence and number of days of use) during Weeks 2, 4, 8, 12, 16, 24, and 32. •Usage of rescue medication (amount taken) during Weeks 2, 4, 8, 12, 16 and 24.
Safety Measures •Adverse Events. •Standard safety assessments (safety laboratory testing [chemistry, hematology], sitting vital signs, electrocardiogram (ECG; 12-lead). •Joint Safety Adjudication outcomes. •Total joint replacements. •Orthostatic (supine / standing) blood pressure assessments. •Survey of Autonomic Symptom scores. •Neurologic exam (Neuropathy Impairment Score [NIS]). •Anti tanezumab antibody assessments. •Physical examinations.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints are listed with the Endpoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker data analysis will be conducted according to the tanezumab biomarker analysis plan.
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 86 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Bulgaria |
Finland |
France |
Germany |
Hungary |
Italy |
Japan |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
Sweden |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last scheduled procedure shown in the Schedule of Activities for the last participant |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |