E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10049038 |
E.1.2 | Term | Metastatic bone pain |
E.1.2 | System Organ Class | 100000004864 |
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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 analgesic efficacy of tanezumab 20 mg SC versus matching placebo SC at Week 8 in subjects, with cancer pain predominantly due to bone metastasis, receiving background opioid therapy. |
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E.2.2 | Secondary objectives of the trial |
Evaluate the safety of tanezumab 20 mg SC versus matching placebo SC in subjects, with cancer pain predominantly due to bone metastasis, receiving background opioid therapy.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Long-term observational study of subjects from tanezumab Study A4091061 (regardless of treatment group) who undergo a total knee, hip, or shoulder replacement during participation in the study (treatment period or safety follow-up period).
Objective: To describe the post-operative outcome of subjects who underwent a total knee, hip, or shoulder replacement while participating in Study A4091061 (treatment period and safety follow-up period). |
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E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 2. Subject is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 3. Male or female, ≥ 18 years of age. 4. Weight is ≥ 40 kg at Screening. 5. Subject has cancer diagnosed as having metastasized to bone or has multiple myeloma. 6. Imaging confirmation of bone metastasis at Screening or within 120 days prior to the Screening visit according to local standard of care (eg, via bone scan, magnetic resonance imaging (MRI), computed tomography (CT) scan, or positron emission tomography-computed tomography (PET-CT) scan). 7. Subject is expected to require daily opioid medication throughout the course of the study. 8. Subject willing to not use prohibited medications (including NSAIDs) throughout the duration of the study. 9. Average Pain Score ≥5 at Screening for the index bone metastasis cancer pain site. 10. Patient’s Global Assessment of Cancer Pain must be “fair”, “poor” or “very poor” at Screening. 11. Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0, 1, or 2 at Screening. 12. Adequate bone marrow function at Screening as defined in the protocol. 13. Adequate renal function at Screening as defined in the protocol. 14. Adequate liver function at Screening as defined in the protocol. 15. Female subjects of childbearing potential and at risk for pregnancy must agree to use at least one highly effective method of contraception throughout the study and for 112 days (16 weeks) after the last dose of assigned subcutaneous study medication.
For the rest of the inclusion criteria, please refer to the protocol |
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E.4 | Principal exclusion criteria |
1. The subject’s pain is related to an oncologic emergency. 2. The subject has brain metastasis or leptomeningeal metastasis. 3. The subject’s pain is primarily classified as neuropathic, visceral or unknown in nature, has resulted from prior cancer therapy, is due to infection or is otherwise not predominantly related to a bone metastasis. 4. Systemic treatment for the primary malignancy or bone metastasis, including chemotherapy, hormonal treatment (eg, gonadotropin-releasing hormone (GnRH) agonists or antagonists), bisphosphonates and denosumab started within 30 days of the first day of the Baseline Assessment Period. 5. Receipt of radiopharmaceutical treatment or radiotherapy for treatment of bone metastasis within 30 days of the first day of the Baseline Assessment Period. 6. Diagnosis of osteoarthritis of the knee or hip as defined by the American College of Rheumatology (ACR) combined clinical and radiographic criteria. 7. Subjects with symptoms and radiographic findings consistent with osteoarthritis in the shoulder. 8. History or radiographic evidence of orthopedic conditions that may increase the risk of joint safety conditions during the study as defined in the protocol. 9. Signs and symptoms of clinically significant cardiac disease within 6 months of the study as defined in the protocol or subjects with any other cardiovascular illness that in the opinion of the investigator would render a subject unsuitable to participate in the study. 10. Subjects with orthostatic hypotension or evidence for an autonomic neuropathy at Screening as defined in the protocol. 11. History, diagnosis, or signs and symptoms of clinically significant neurological disease as described in the protocol. 12. Planned surgical procedure during the duration of the study 13. Subjects considered unfit for surgery as defined in the protocol.
For the rest of the exclusion criteria, please refer to the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline to Week 8 in the daily average pain intensity in the index bone metastasis cancer pain site. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to the protocol |
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E.5.2 | Secondary end point(s) |
Efficacy Measures: -Change from Baseline to Weeks 1, 2, 4, 6, 12, 16 and 24 in the daily average pain intensity NRS score in the index bone metastasis cancer pain site. -Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily worst pain intensity NRS score in the index bone metastasis cancer pain site. -Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the weekly average pain intensity NRS score in non-index cancer pain sites. -Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the weekly worst pain intensity NRS score in non-index cancer pain sites. -Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily average pain intensity NRS score in the non-index visceral cancer pain sites. -Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily worst pain intensity NRS score in the non-index visceral cancer pain site. -Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the Brief Pain Inventory (BPI) average pain scores obtained at study visits. -Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the BPI worst pain scores obtained at study visits. -Response as defined by a ≥30%, ≥50%, ≥70%, and ≥ 90% reduction from Baseline in the daily average and daily worst pain intensity NRS score in the index bone metastasis cancer pain site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24. -Change from Baseline in Patient’s Global Assessment of Cancer Pain at Weeks 2, 4, 8, 16 and 24. -Response defined as an improvement of ≥ 2 points in Patient's Global Assessment of Cancer Pain at Weeks 2, 4, 8, 16 and 24. -Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the BPI Pain Interference with Function Composite Score and individual pain interference item scores obtained at study visits. -EuroQol 5 Dimension (EQ-5D-5L) dimensions and overall health utility score at Baseline and Weeks 8, 16 and 24.
Opioid Use and Opioid Adverse Effects Measures
-Average daily total opioid consumption (in mg of morphine equivalent doses) at Weeks 1, 2, 4, 6, 8, 12, 16 and 24. -Average number of doses of rescue medication required per week at Weeks 1, 2, 4, 6, 8, 12, 16 and 24. -Change from Baseline in the weekly Opioid-Related Symptom Distress Scale at Weeks 2, 4, 8, 16, and 24.
Safety Measures
-Adverse events. -Standard safety assessments (safety laboratory testing [chemistry, hematology], sitting vital signs, ECG [12-lead]). -Orthostatic (supine/standing) blood pressure assessment. -Weight measurements. -Physical examinations. -Joint safety adjudication outcomes. -Total joint replacements. -Neurologic examination (Neuropathy Impairment Score [NIS]). -Survey of Autonomic Symptom scores. -Anti-drug antibody (ADA) assessments.
Refer to protocol for other endpoints |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to the protocol |
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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 | No |
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 |
Serum and urine osteoarthritis biomarker concentrations. |
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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 | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Argentina |
Australia |
Austria |
Brazil |
Chile |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Japan |
Korea, Republic of |
Poland |
Romania |
Slovakia |
Spain |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 27 |