| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| osteoarthritis of the knee and hip |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020108 |
| E.1.2 | Term | Hips osteoarthritis |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10023476 |
| E.1.2 | Term | Knee osteoarthritis |
|
| 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 analgesic efficacy of tanezumab 10 mg and 5 mg
administered IV every 8 weeks compared to placebo at Week 16.
• Demonstrate non-inferiority and, if warranted, superior analgesic efficacy of
tanezumab 10 mg and 5 mg administered IV every 8 weeks compared to
oxycodone HCl controlled release (CR) tablets (Oxycontin) 10-40 mg every 12
hours (q12h) at Week 16. |
|
| E.2.2 | Secondary objectives of the trial |
• Evaluate the safety and tolerability up to Week 18 of tanezumab 10 mg and 5 mg
administered IV every 8 weeks. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patient eligibility should be reviewed and documented by an appropriately qualified
member of the investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study.
1. Patients must consent in writing to participate in the study by signing and dating an Informed Consent Document indicating that the patient has been informed of all
pertinent aspects of the study prior to completing any of the Screening procedures;
2. Male or female of any race, 18-75 years of age, inclusive;
3. Patients must have a diagnosis of OA of the knee or hip based on American College of Rheumatology criteria with X-ray confirmation (a Kellgren-Lawrence24 x-ray grade of ≥2) X-rays taken within the last 12 months may be used for confirmation;
4. Patients must regularly use analgesic medication, defined as > 4 days per week for the last month prior to Screening. Analgesic medication may consist of NSAIDs,
selective COX-2 inhibitors, opioids or combinations thereof. Acetaminophen cannot
be the sole analgesic used;
5. At least one of the following three criteria must be met.
• Non-opioid pain medications (eg, NSAIDs) or opioid medications at prescribed doses less than or equal to a morphine equivalent of 90 mg/day (oxycodone 60 mg/day) have not provided adequate pain relief or
• Patient are unable to take non-opioid pain medications (eg, NSAIDs) or
• Patients are candidates for or seeking invasive interventions such as intra-articular
injections, knee or hip arthroplasty, or knee or hip replacement surgery;
6. WOMAC Pain subscale NRS ≥4 in the index knee or index hip at Screening with or
without analgesic medication;
7. WOMAC Pain subscale NRS ≥5 in the index knee or index hip at Baseline;
8. An increase of ≥1 point in WOMAC Pain subscale NRS in the index knee or index
hip from Screening to Baseline;
9. WOMAC Physical Function subscale NRS ≥4 in the index knee or index hip at Baseline;
10. Patient Global Assessment of Osteoarthritis must be “fair,” “poor,” or “very poor” at Baseline;
11. Patients must be willing to discontinue all pain medications for OA except rescue
medication and not use prohibited pain medications throughout the duration of the
study except as permitted per Protocol;
12. Female patients must meet one of the following criteria:
a. Female patients of non-childbearing potential:
• Must be post-menopausal, defined as women who are ≥45 years old with
amenorrhea for 24 consecutive months (regardless of FSH levels), or women who are amenorrheic for at least 1 year AND have a serum Follicle-Stimulating Hormone (FSH) level greater than 30 IU/L at Screening; or
• Must be surgically sterile, defined as having had a hysterectomy and/or
bilateral oophorectomy.
b. Female patients of child-bearing potential:
• Must not be pregnant or lactating; and
• Must be abstinent or use adequate contraception (2 forms of birth control,
one of which must be a barrier method); and
• Must have a negative serum pregnancy test at Screening (within 30 days prior to Baseline) and a negative serum and urine pregnancy test at Baseline prior to initial dosing.
Male patients must agree that they and their female spouses / partners will use
adequate contraception (2 forms of birth control, one of which must be barrier
method) or be of non-childbearing potential.
Females of child-bearing potential and males must be willing to use approved methods of contraception from commencement of screening procedures until 16 weeks after the last dose of IV study medication.
In the event of indeterminate or anomalous results on pregnancy/FSH testing or
issues surrounding contraceptive requirements, study management should be
contacted and will make the final decision as to the adequacy/need for contraception.
13. Patients must be willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
1. Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to be pregnant
2. Body mass index (BMI) of >39 kg/m2
3. History of inflammatory joint diseases, crystalline disease (gout or pseudogout), endocrinopathies, metabolic joint diseases, lupus erythematosus, rheumatoid arthritis, joint infections, neuropathic disorders, avascular necrosis, Paget’s disease, or tumors
4. Significant trauma or surgery to the index joint within the previous year;
5. Planned surgical procedure
6. Largely or wholly incapacitated
7. Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy
8. Other pain that may confound assessments or self-evaluation of pain
9. History of cancer within the last 5yrs
10. Signs and symptoms of clinically significant cardiac disease including but not limited to
•Ischemic cardiac disease
•Surgery or stent placement for coronary artery disease in the 6 months prior to
Screening
•New York Heart Association (NYHA) Class III or IV congestive heart failure or known left ventricular dysfunction with ejection fraction ≤35%, cardiomyopathy, myocarditis in the 6 months prior to Screening
•Resting tachycardia (heart rate ≤120) or resting bradycardia (heart rate ≤45) on ECG at Screening or Baseline
•QTc interval >500 msec in the absence of bundle branch block or paced rhythm
•Any CV illness that would render a patient unsuitable to participate
11. Diagnosis of a transient ischemic attack in the 6 months or diagnosis of stroke with residual deficits (eg, aphasia, substantial motor or sensory deficits)
12. History, diagnosis, or signs and symptoms of clinically significant neurological
disease, including but not limited to
•Alzheimer’s disease or other types of dementia
•Clinically significant head trauma within the past year
•Peripheral neuropathy
•Multiple sclerosis
•Epilepsy or seizure
•Myopathy
13. History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder, including but not limited to
•Psychotic disorders
•Somatoform disorders
•Bipolar disorders
•Any other psychiatric illness that would render a patient unsuitable
14. Hospital admission for depression or suicide attempt within 5 years of Screening or active, severe major depression at Screening
15. History of known alcohol, analgesic or non-narcotic drug abuse within 2 years
16. Any history of known opioid or narcotic abuse
17. Previous exposure to exogenous NGF or to an anti-NGF antibody
18. Exposure to opioids at doses exceeding a morphine equivalent of 90 mg/day
(oxycodone 60 mg/day) within 30 days prior to Screening is exclusionary
19. Use of any analgesic from Screening to the start of the Initial Pain Assessment Period (the 3 days prior to Randomization/Baseline) without a sufficient washout
20. History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein
21. History of intolerance or hypersensitivity to 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
22. History of intolerance or hypersensitivity to oxycodone or any of its excipients
23. Patients taking >325 mg/day of aspirin (or any salicylate containing medications).
24. Existence of a medical condition for which the use of oxycodone is contraindicated
25. Resting, sitting blood pressure (BP) ≥160 mm Hg in systolic pressure or ≥100 mm Hg or diastolic blood pressure at Screening.
26. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3.0 times the upper limit of normal, or creatinine exceeding 1.7 mg/dL (150 µmol/L) in men or
1.5 mg/dL (133 µmol/L) in women, or hemoglobin A1c ≥10% at Screening.
27. Presence of drugs of abuse (including prescription medications without a valid
prescription), other illegal drugs or marijuana in the urine toxicology screen obtained
at Screening is exclusionary; presence of opioids in urine toxicology screen for
patients taking prescribed opioids is allowed
28. Positive Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) tests at
Screening indicative of current or past infection
29. Oral or intramuscular corticosteroids within 30 days
30. Intra-articular corticosteroid injection in the index knee or index hip within 12 weeks, or to any other joint within 30 days
31. Intra-articular hyaluronic acid injection to the index joint within 30 days
32. Use of biologics other than study medication,
33. Use of any investigational medication within 30 days prior to the Initial Pain
Assessment Period (3 months for investigational biologics) or plans to receive an
investigational medication other than the study medication during the course of this
study
34. Any other condition, which in the opinion of the Investigator, would put the patient at increased safety risk or otherwise make the patient unsuitable for this study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•The primary endpoint for the tanezumab vs placebo comparison is the change
from Baseline to Week 16 in the WOMAC Pain subscale (primary objective 1).
•The primary endpoint for the tanezumab vs oxycodone CR comparison is the
change from Baseline to Week 16 in the WOMAC Pain subscale (primary
objective 2). |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 59 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 28 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
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