A Randomised, Double-blind, Placebo-controlled, Dose-response Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 345
- 试验地点
- 1
- 主要终点
- Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12
研究概览
简要总结
This is a Phase IIb randomised, double-blind, placebo-controlled, dose-response study in participants with painful osteoarthritis (OA) of the knee. The study will assess the safety and efficacy of multiple doses of MEDI7352 compared to placebo, as well as the pharmacokinetics, pharmacodynamics and immunogenicity of MEDI7352 in participants with moderate to severe chronic pain persistent for 3 months or more not adequately controlled by standard of care treatments.
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)
盲法说明
All participants will be centrally assigned to randomised IP using an Interactive Response Technology/Randomisation and Trial Supply Management (IRT/RTSM) system. Before the study is initiated, telephone number and call-in directions for IRT and/or log in information and directions for RTSM will be provided to each site.
The IRT/RTSM will provide investigator(s) or appropriate study personnel with kit identification number to be allocated to participant at IP dosing visit.
Details for this will be described in IRT/RTSM user manual that will be provided to each centre.
All participants, investigators, and study personnel involved in conduct of the study will be blinded to treatment assignment. The unblinded study personnel (eg, site pharmacist) will not participate in study procedures or data analysis prior to unblinding of study data to all study-related personnel. Unblinded AstraZeneca personnel who are not otherwise involved in study will prepare data for review and interim analyses.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must understand the nature of the study and must give signed and dated written informed consent prior to the initiation of any study procedures, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- •For participants participating in the optional genetic research, a separate signed and dated optional genetic research ICF must be provided prior to collection of samples for optional genetic research that supports the Genomics Initiative. If a participant declines to participate in the genetic research, this will have no influence on the ability of a participant to participate in the study.
- •The participant should be willing and able to understand and comply with all protocol-specified restrictions and procedures and be able to use an electronic patient-reported outcome (ePRO) device as judged by the investigator.
- •The participant must be considered likely to comply with the study protocol and to have a high probability of completing the study, as judged by the investigator.
- •The participant must be willing and able to discontinue all analgesic therapy with nonsteroidal anti-inflammatory drugs (NSAID) or cyclooxygenase-2 (COX-2) inhibitors from the start of the washout period until the end of the FU period. This includes over-the-counter (OTC) pain medications and topical analgesics that contain an NSAID or COX-2 inhibitor.
排除标准
- •Requires current treatment with another biologic therapeutic agent, disease-modifying antirheumatic drug (DMARD), or other immunosuppressants.
- •Previously received any form of anti-nerve growth factor (NGF); received anti-tumour necrosis factors (TNFs) including but not limited to golimumab, certolizumab, infliximab, adalimumab, etanercept, or rituximab within 12 months prior to screening, or other biological DMARDs (including but not limited to abatacept, tocilizumab, and tofacitinib), or other immunosuppressants within 6 months prior to screening (with the exception of inhaled or topical corticosteroids).
- •Currently receiving strong opioids for any indication.
- •Participation in another clinical study with an IP or device within 60 days or 5 half-lives, whichever is longer, prior to screening.
- •Plasma donation within 28 days of screening or any blood donation or blood loss > 500 mL within 2 months of screening.
- •Previous allogeneic bone marrow or stem cell transplant.
- •Received nonleukocyte-depleted whole blood transfusion within 120 days of the genetic research sample collection, if participating in the optional genetic research.
- •Involvement in the planning and/or conduct of the study.
研究组 & 干预措施
MEDl7352 Dose 1
Participants received 6 doses of subcutaneous (SC) MEDl7352 Dose 1 injection once every 2 weeks (Q2W) during a 12-week parallel-group treatment period.
干预措施: MEDI7352 (Drug)
MEDl7352 Dose 2
Participants received 6 doses of SC MEDl7352 Dose 2 injection Q2W during a 12-week parallel-group treatment period.
干预措施: MEDI7352 (Drug)
MEDl7352 Dose 3
Participants received 6 doses of SC MEDl7352 Dose 3 injection Q2W during a 12-week parallel-group treatment period.
干预措施: MEDI7352 (Drug)
MEDl7352 Dose 4
Participants received 6 doses of SC MEDl7352 Dose 4 injection Q2W during a 12-week parallel-group treatment period.
干预措施: MEDI7352 (Drug)
Placebo
Participants received 6 doses of SC placebo injection matched to MEDl7352 Q2W during a 12-week parallel-group treatment period.
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12
时间窗: Baseline (Day -7 to Day -1, inclusive) through Week 12
Change from baseline in weekly average of daily NRS pain score to Week 12 is reported. The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = "no pain" to 10 = "most severe pain imaginable over the previous 24 hours". This was recorded on a daily basis at approximately the same time every morning via electronic patient recorded outcome (ePRO) diary. A two-step multiple imputation procedure was used to address missing post-baseline scores.
次要结局
- Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12(Week 0 (Day 1; baseline) through Week 12)
- Change From Baseline in WOMAC Physical Function Subscale to Week 12(Week 0 (Day 1; baseline) through Week 12)
- Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12(Week 0 (Day 1; baseline) through Week 12)
- Change From Baseline in WOMAC Pain Subscale Over Time(Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126))
- Change From Baseline in WOMAC PF Subscale Over Time(Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126))
- Change From Baseline in WOMAC Overall Score Over Time(Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126))
- Change From Baseline in WOMAC Stiffness Scores Over Time(Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126))
- Change From Baseline in PGA of OA Over Time(Baseline, Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), and 18 (Day 126))
- Percentage of Participants With Improvement of >= 2 Points in PGA of OA(Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126))
- Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time(Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126))
- Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time(Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126))
- Serum Concentration of MEDI7352(Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224)
- ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline(Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(Day 1 through 41 weeks (maximum observed duration))
- Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs(Day 1 through 41 weeks (maximum observed duration))
- Total Neuropathy Score-Nurse (TNSn) Over Time(Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 196), and 32 (Day 224))
- Number of Participants With Abnormal Vital Signs Reported as TEAEs(Day 1 through 41 weeks (maximum observed duration))
- Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs)(Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 168), and 32 (Day 224))
- Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition(Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126))
- Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time(Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126))
- Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time(Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126))
- Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352(Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224)
- Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination(Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 18 (Day 126), 28 (Day 168), 32 (Day 224), and 36 (Day 252))
- Change From Baseline in Weight (kg) to Week 12(Baseline (Day -45 to -1) and Week 12)
- Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score(Baseline (Day 1; Week 0) and Day 252 (Week 36))
- Number of Participants With Injection Site Reactions(Day 1 through 41 weeks (maximum observed duration))
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs(Day 1 through 41 weeks (maximum observed duration))
- Change From Baseline in C-reactive Protein Level to Week 12(Baseline (Day -7 to -1, inclusive) and Week 12)
- Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints(Baseline (Day -45 to -1) and Week 32)