A Phase 3 Randomized, Double-blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Long-Term Safety and the Efficacy of Fasinumab in Patients With Pain Due to Osteoarthritis of the Knee or Hip
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 5,331
- 试验地点
- 8
- 主要终点
- Number of Participants With Any Adverse Event (AE) up to Week 72
研究概览
简要总结
The primary objective of the study is to describe the safety and tolerability of fasinumab, including adverse events of special interest (AESIs), in patients with pain due to radiographically-confirmed OA of the knee or hip.
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
- •Male or female ≥18 years of age at the screening visit
- •Clinical diagnosis of OA of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2) for the index joint at the screening visit
- •Moderate to severe pain in the index joint defined as a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) average pain subscale score of ≥4
- •A history of 12 weeks of analgesic use for OA of the knee or hip
- •History of regular use of analgesic medications for OA pain
排除标准
- •History or presence at the screening visit of non OA inflammatory joint disease
- •History or presence on imaging of arthropathy, stress fracture, recent stress fracture, neuropathic joint arthropathy, hip dislocation, knee dislocation, congenital hip dysplasia with degenerative joint disease, extensive subchondral cysts, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas or pathologic fracture during the screening period
- •Signs or symptoms of carpal tunnel syndrome within 6 months of screening
- •Patient is not a candidate for MRI
- •Is scheduled for a joint replacement surgery to be performed during the study period
- •Systemic (i.e., oral or intramuscular) corticosteroids within 30 days prior to the screening visit.
- •History or presence at the screening visit of multiple sclerosis, autonomic neuropathy, diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy
- •History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy
- •Pregnant or breast-feeding women
- •Women of childbearing potential who have a positive pregnancy test result or do not have their pregnancy test result at baseline
- •Note: Other protocol defined Inclusion/Exclusion criteria apply
研究组 & 干预措施
Fasinumab dosing regimen 1
干预措施: Fasinumab (Drug)
Fasinumab dosing regimen 2
干预措施: Fasinumab (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Any Adverse Event (AE) up to Week 72
时间窗: Baseline up to week 72
Number of Participants With Any Serious AE up to Week 72
时间窗: Baseline up to week 72
Number of Participants With Any Serious TEAE
时间窗: Baseline up to week 52
Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation
时间窗: Baseline up to week 72
Any participant with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an adverse event of special interest (AESI).
Number of Participants With Any Treatment-Emergent Adverse Event (TEAE)
时间窗: Baseline up to week 52
Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria
时间窗: Baseline up to week 52 and week 72
DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee.
Number of Participants With Sympathetic Nervous System (SNS) Dysfunction
时间窗: Baseline up to week 72
Potential events of sympathetic nervous system (SNS) dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.
Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery
时间窗: Baseline up to weeks 52, 72, and end of study (52 weeks post last dose)
All joint replacement surgery events regardless of cause at weeks 52 and 72. An end of study phone contact was also conducted approximately 52 weeks following the last dose of study drug.
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52
时间窗: Baseline to week 52
Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the treatment period were reported. Clinical significance was determined by the investigator.
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72
时间窗: End of treatment up to week 72
Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the post-treatment period were reported. Clinical significance was determined by the investigator.
Number of Participants With Anti-drug Antibody (ADA) up to Week 72
时间窗: Baseline up to week 72
Immunogenicity was characterized by ADA responses \& titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses less than (\<) 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, greater than or equal to (≥) 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the fasinumab ADA assay post first dose when baseline results = negative or missing.
Number of Participants With Adjudicated Arthropathy (AA)
时间窗: Baseline up to week 52 and week 72
Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.
Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score
时间窗: Baseline to Week 16
The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations.
Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score
时间窗: Baseline to Week 16
The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations.
次要结局
- Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis(Baseline to Week 16)
- Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score(Baseline to Week 16)