NCT02609828已完成3 期
A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB (PF-04383119) IN SUBJECTS WITH CANCER PAIN PREDOMINANTLY DUE TO BONE METASTASIS RECEIVING BACKGROUND OPIOID THERAPY
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 156
- 试验地点
- 87
- 主要终点
- Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8
研究概览
简要总结
The purpose of this study is to determine whether tanezumab is effective in the treatment of cancer pain due to bone metastasis in patients already taking background opioid therapy.
详细描述
This is a randomized, double-blind, placebo-controlled, multicenter, parallel-group Phase 3 study in cancer subjects requiring treatment with background opioids for pain due to bone metastasis.
Approximately 144 subjects will be randomized to one of 2 treatment groups in a 1:1 ratio (approximately 72 subjects per group). Subjects will receive a total of 3 subcutaneous injections, separated by 8 weeks in addition to background opioids administered throughout the study.
Treatment groups will include: 1. Placebo SC (matching tanezumab SC) in addition to background opioid therapy. 2. Tanezumab 20 mg SC in addition to background opioid therapy.
The study consists of three periods: Pre-Treatment (up to 37 days), Double-Blind Treatment (24 weeks) and Safety Follow-up (24 weeks).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Personally signed and dated informed consent document.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Male or female, ≥18 years of age
- •Weight ≥40 kg at Screening
- •Cancer diagnosed as having metastasized to bone or multiple myeloma.
- •Imaging confirmation of bone metastasis at Screening or within 120 days prior to the Screening visit.
- •Expected to require daily opioid medication throughout the course of the study.
- •Willing to not use prohibited medications (including NSAIDs) throughout the duration of the study.
- •Average Pain Score ≥5 at Screening for the index bone metastasis cancer pain site.
- •Patient's Global Assessment of Cancer Pain of "fair", "poor" or "very poor" at Screening.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0, 1, or 2 at Screening.
- •Adequate bone marrow, renal and liver function at Screening.
- •International Normalized Ratio (INR) or prothrombin time (PT) <1.5 x ULN at Screening unless being treated with anticoagulant medication.
- •Females must either be not of childbearing potential or, if of childbearing potential and at risk for pregnancy, must be willing 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.
排除标准
- •Pain related to an oncologic emergency.
- •Brain metastasis or leptomeningeal metastasis.
- •Presence of hypercalcemia at Screening.
- •Pain primarily classified as not predominantly related to a bone metastasis.
- •Systemic treatment for the primary malignancy or bone metastasis started within 30 days of the Baseline Assessment Period.
- •Chemotherapies associated with peripheral neuropathy (ie, paclitaxel, docetaxel, oxaliplatin, cisplatin, vincristine, thalidomide or bortezomib) are prohibited during the study from 30 days prior to the first day of the Baseline Assessment Period to Week
- •Receipt of radiopharmaceutical treatment or radiotherapy for treatment of bone metastasis within 30 days of the Baseline Assessment Period.
- •Concurrent adjuvant analgesics unless started at least 30 days prior to the start of the Baseline Assessment Period and maintained at a stable dose.
- •Diagnosis of osteoarthritis of the knee or hip or findings consistent with osteoarthritis in the shoulder.
- •History of significant trauma or surgery to a major joint within one year prior to Screening.
- •History of osteonecrosis or osteoporotic fracture.
- •X-ray evidence at Screening of: 1) rapidly progressive osteoarthritis, 2) atrophic or hypotrophic osteoarthritis, 3) subchondral insufficiency fracture, 4) spontaneous osteonecrosis of the knee (SPONK), 5) osteonecrosis, or 6) pathologic fracture.
- •Signs and symptoms of clinically significant cardiac disease.
- •Evidence of orthostatic hypotension at Screening or at Baseline prior to randomization.
- •Diagnosis of a transient ischemic attack in the 6 months prior to Screening or diagnosis of stroke with significant residual deficits.
- •History, diagnosis, or signs and symptoms of clinically significant neurological disease.
- •Total impact score of >7 on the Survey of Autonomic Symptoms (SAS) at Screening.
- •Past history of carpal tunnel syndrome (CTS) with signs or symptoms of CTS in the one year prior to Screening.
- •History of significant alcohol, analgesic, or narcotic substance abuse within the six months prior to Screening.
- •Planned surgical procedure during the duration of the study.
- •Considered unfit for surgery or not willing to undergo joint replacement surgery if required.
- •Known hypersensitivity to opioids or an underlying medical condition contraindicating opioid use.
- •History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
- •Previous exposure to exogenous nerve growth factor or to an anti-nerve growth factor antibody.
- •Presence of drugs of abuse, prescription medications without a valid prescription or other illegal drugs at Screening.
- •Positive Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) tests at Screening indicative of current infection.
- •Investigational site staff members and their family members, or Pfizer employees directly involved in the conduct of the trial.
- •Participation in other studies involving investigational drug(s) within 30 days (or 90 days for investigational biologics) before Baseline Assessment Period and/or during study participation.
- •Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential who are unwilling or unable to use one (1) highly effective method of contraception throughout the study and for 112 days after last dose of investigational product.
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality.
研究组 & 干预措施
Arm 1
Experimental
Tanezumab 20 mg subcutaneously
干预措施: Tanezumab (Drug)
Arm 2
Placebo Comparator
Placebo matched to active treatment subcutaneously
干预措施: Tanezumab (Drug)
结局指标
主要结局
Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8
时间窗: Baseline, Week 8
Daily average pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The participants recorded their daily average pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on interactive response technology (IRT) diaries. Baseline daily average pain intensity value was mean of the daily average pain intensity NRS scores during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Week 8 daily average pain intensity value was the mean of the daily average pain intensity NRS scores recorded for each of the 7 days prior to the Week 8.
次要结局
- Average Daily Total Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24(Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24(Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Change From Baseline in the 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(Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Change From Baseline in Participant's Global Assessment of Cancer Pain (PGA-CP) at Weeks 2, 4, 8, 16 and 24(Baseline, Weeks 2, 4, 8, 16 and 24)
- Change From Baseline in the Weekly Opioid-Related Symptom Distress Scale (OR-SDS) at Weeks 2, 4, 8, 16, and 24(Baseline, Weeks 2, 4, 8, 16, and 24)
- Change From Baseline in the Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 12, 16 and 24(Baseline, Weeks 1, 2, 4, 6, 12, 16 and 24)
- Change From Baseline in the Weekly Average Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24(Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Number of Participants With Cumulative Reduction of >=30, 50, 70 and 90 Percent (%) From Baseline in Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24(Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Number of Participants With Reduction of >=30, 50, 70 and 90% From Baseline in 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(Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Number of Participants With Reduction of >=2 Points From Baseline in PGA-CP Scores at Weeks 2, 4, 8, 16 and 24(Baseline, Weeks 2, 4, 8, 16 and 24)
- Change From Baseline in the Weekly Worst Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24(Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Change From Baseline in the Daily Average Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24(Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Average Number of Doses of Rescue Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24(Weeks 1, 2, 4, 6, 8, 12, 16 and 24)
- Number of Participants With Laboratory Abnormalities (Normal Baseline)(Baseline (Day 1, before dosing) up to Week 48)
- Number of Participants With Categorical Change From Baseline to Last Post-Baseline in Sitting Systolic and Diastolic Blood Pressure During Treatment Period(Baseline (Day 1, before dosing) up to Week 24)
- Number of Participants With Confirmed Orthostatic Hypotension(Baseline (Day 1, before dosing), Weeks 8, 16, 24 and 48)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Day 1 of dosing up to 24 weeks post last dose (maximum up to Week 48))
- Number of Participants With Clinically Significant Findings in Weight Measurement, Counted as an AE(Day 1 of dosing up to maximum of Week 48)
- Number of Participants With Abnormal Physical Examination at Screening(Screening (up to 37 days prior to Day 1))
- Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Anti-Drug Antibodies (NAb)(Baseline (Day 1, before dosing) up to Week 48)
- Number of Participants With Laboratory Abnormalities (Abnormal Baseline)(Baseline (Day 1, before dosing) up to Week 48)
- Number of Participants With Individual Adjudicated Joint Safety Outcome/Event(During the study, maximum up to Week 48)
- Number of Participants With Categorical Summary of Electrocardiogram (ECG) (QTC) Data(Baseline (Day 1, before dosing) up to Week 24)
- Number of Participants With At Least 1 Total Joint Replacements (TJR)(During the study, maximum up to Week 48)
研究者
研究点 (87)
Loading locations...
相似试验
已完成
3 期
Tanezumab In Osteoarthritis Of The Knee (2)ArthritisOsteoarthritisNCT00830063Pfizer832
已完成
3 期
Efficacy and Safety of a Subcutaneous Tanezumab Titration Dosing Regimen in Subjects With Moderate to Severe Osteoarthritis of the Hip or KneeOsteoarthritis, HipOsteoarthritis, KneeNCT02697773Pfizer698
终止
3 期
Efficacy And Safety Study Of Tanezumab Subcutaneous Administration In Osteoarthritis - A Subcutaneous/Intravenous Bridging StudyArthritisPainOsteoarthritisNCT01089725Pfizer385
已完成
3 期
A Phase 3 Study of Tanezumab for Chronic Low Back PainLow Back PainNCT02528253Pfizer1,832
进行中（未招募）
2 期
Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to SchwannomatosisSchwannomatosisPainNCT04163419Massachusetts General Hospital9