A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of the Efficacy and Safety of Fremanezumab for Treatment of Patients With Fibromyalgia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 189
- 试验地点
- 49
- 主要终点
- Change From Baseline in the Weekly Average of the Daily Average Pain Intensity-Numerical Rating Scale (PI-NRS) Score Over the Past 24 Hours at Week 12
研究概览
简要总结
The primary objective of the study is to estimate the treatment effect of fremanezumab administered subcutaneously (SC) in reducing pain in adult participants with fibromyalgia (FM). A secondary objective is to evaluate the effect of fremanezumab on other efficacy measures, including pain, quality of life, sleep, fatigue, improvement in health, physical functioning, and mood. Another secondary objective is to evaluate the safety and tolerability of fremanezumab administered SC in adult participants with FM.
The total duration of participant participation in the study is planned to be 21 weeks, consisting of a screening period of up to 5 weeks (ranging from 17 to 35 days), and a double-blind treatment period of 16 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •approved for study participation by the Fibromyalgia Eligibility Review Committee
- •body mass index of 18.5 to 45 kilograms (kg)/square meter (m^2) and a body weight ≥45 kg
- •agree to use only acetaminophen as rescue medication for FM-related pain (up to 1000 mg per dose and not to exceed 3000 mg/day for any indication throughout the study period)
- •non-pharmacologic interventions (including normal daily exercise routines, chiropractic care, physical therapy, psychotherapy, and massage therapy) are unchanged for a minimum of 30 days prior to screening and will remain unchanged throughout the study
- •agree to maintain a usual and unchanged physical exercise regimen
- •must be of nonchildbearing potential or, defined as:
- •women surgically sterile by documented complete hysterectomy, bilateral oophorectomy, or
- •bitubal ligations or confirmed to be postmenopausal (at least 1 year since last menstrual period) and
- •menopausal women confirmed by a follicle-stimulating hormone >35 units (U)/liter (L)
- •men surgically sterile by documented vasectomy OR
- •If of childbearing potential, patients must meet any of the following criteria:
- •must use highly effective contraception method with their partners during the entire study period and for 5 months after the last dose of the study drug.
- •sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period.
- •female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at screening (confirmed by urine dipstick β-HCG pregnancy test at baseline).
- •must agree not to participate in another interventional study from the screening period through the end of study (EOS) visit o Additional criteria apply, please contact the investigator for more information
排除标准
- •unable or unwilling to discontinue/washout of prohibited medications
- •ongoing pain that would confound or interfere with the assessment of the participant's FM pain or require excluded therapies during the participant's participation in this study.
- •surgery planned during the study period
- •receiving prophylactic treatment for migraine-related disorders, including topiramate, valproic acid, onabotulinumtoxinA, amitriptyline, and nortriptyline
- •known history of clinically significant or unstable hematologic, cardiac, or thromboembolic events
- •known history of suicide attempt, suicidal behavior, or suicidal ideation within the last 12 months
- •lifetime history of any psychotic and/or bipolar disorder
- •current, untreated, moderate or severe major depressive disorder and/or anxiety
- •known history of hypersensitivity reactions to injected proteins, including monoclonal antibodies (mAbs) and animal venoms, or a history of Stevens-Johnson Syndrome/toxic epidermal necrolysis syndrome o Additional criteria apply, please contact the investigator for more information
研究组 & 干预措施
Placebo
Participants will receive placebo matching to fremanezumab SC on Days 1, 29, 57, and 85.
干预措施: Placebo (Drug)
Fremanezumab Dose A
Participants will receive fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
干预措施: Fremanezumab (Drug)
Fremanezumab Dose B
Participants will receive fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
干预措施: Fremanezumab (Drug)
结局指标
主要结局
Change From Baseline in the Weekly Average of the Daily Average Pain Intensity-Numerical Rating Scale (PI-NRS) Score Over the Past 24 Hours at Week 12
时间窗: Baseline, Week 12
The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indicating more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. Baseline was defined as the last 14 days before the first dose of study drug.
次要结局
- Time to Withdrawal of Treatment Due to AEs(Baseline up to Week 16)
- Number of Participants Who Experienced ≥30% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12(Week 12)
- Change From Baseline in the Weekly Average of Daily Worst PI-NRS Score Over Past 24 Hours at Week 12(Baseline, Week 12)
- Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Serum Chemistry Value(Baseline up to Week 16)
- Number of Participants With at Least 1 Potentially Clinically Significant Urinalysis Abnormalities(Baseline up to Week 16)
- Number of Participants With at Least 1 Physical Examination Abnormal Finding(Baseline up to Week 16)
- Number of Participants With at Least 1 Injection Site AE(Baseline up to Week 16)
- Time to Withdrawal of Treatment Due to Lack of Efficacy(Baseline up to Week 16)
- Change From Baseline in the Individual Components of the Fibromyalgia Impact Questionnaire Revised (FIQR) Score: Symptom Subscore, Impact Subscore, and Functional Subscore at Week 12(Baseline, Week 12)
- Responder Rate of the Patient Global Impression of Change (PGIC) Rating: Number of Participants Who Were Much Improved or Very Much Improved at Week 12(Week 12)
- Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form (SF) 8a T-score at Week 12(Baseline, Week 12)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Week 16)
- Number of Participants With at Least 1 Clinically Significant Abnormal Vital Signs Value(Baseline up to Week 16)
- Change From Baseline in the PROMIS Physical Function SF 12a Scale Score at Week 12(Baseline, Week 12)
- Change From Baseline in the PROMIS Fatigue SF 8a T-Score at Week 12(Baseline, Week 12)
- Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Hematology Value(Baseline up to Week 16)
- Number of Participants With Hypersensitivity/Anaphylaxis Reactions(Baseline up to Week 16)
- Number of Participants Who Experienced ≥50% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12(Week 12)
- Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters(Baseline to Week 16)