A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of ISIS 546254 for Preventive Treatment of Chronic Migraine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Migraine Days
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and changes in the number of migraine and headache days with repeated subcutaneous administration of IONIS-PKKRx (ISIS 546254) or placebo in subjects with chronic migraine.
详细描述
This is a double-blind, placebo-controlled, randomized, multi-center study in subjects with chronic migraine. The study will consist of 7 office visits, 6 Sample collection visits and 3 phone call assessments. Subjects agreeing to participate in the study and meeting the entry criteria assessed at the screening visit, will begin a 28 day baseline period to confirm their diagnosis, and establish a baseline frequency of migraine and headache days. During the baseline period, subjects will continue treating their migraines in their usual manner. They will monitor headache activity, migraine related symptoms, and medication usage with an electronic daily headache diary.
Subjects who, after completing the baseline, continue to meet entrance criteria will be eligible to enter into the 4 month treatment phase. They will be randomized according to the Clinvest generated randomization schedule. A total of 30 randomized subjects will enter the treatment phase receiving IONIS-PKKRx (ISIS 546254; SC) or placebo in a 1:1 design. Study drug or placebo will be administered weekly for 16 weeks. A short phone call to assess any treatment related adverse events will take place 1 and 2 days after randomization. Daily electronic diary assessments will collect headache frequency and severity, associated migraine symptoms, acute medication usage, and the emergence of unusual symptoms and adverse events. Subjects will return to the site at weeks 4, 8, and 12 for investigational product (IP) accountability/dispensing, medication and medication updates, biomarker/lab sample collection, and assessment of adverse events. An end of treatment visit will take place 16 weeks after randomization.
Subjects will have a follow-up safety visit one month after their last dosage of IP ) for assessment of any adverse events (AE) and satisfaction and a final safety phone call 2 months following their last office visit (3 months after last dose of IP) for assessment of any adverse events (AE). Subjects will continue to complete headache diaries through Visit 7. Subjects will also have hematology samples collected every other week starting after Visit 2 through Day 154.
Safety and tolerability will be monitored by the Investigators. Patients who discontinue study treatment prematurely should complete any follow-up visits associated with the most recent dose and should move into and complete the Follow-up Phase.
Subjects will undergo sampling for (pharmacokinetics) PK, coagulation, chemistry, hematology, and optional future biomedical research, as specified in the schedule of procedures.
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
- Double (Participant, Investigator)
盲法说明
At randomization (Visit 2), neither the subject nor the investigator will be aware to which treatment group the subject has been assigned. Investigational product will be drawn and administered in a double blind format. If needed, for safety and proper treatment of the subject, the investigator can unblind the subject's treatment assignment to determine which treatment has been assigned and institute appropriate follow-up care. When possible, Sponsor and Clinvest should be notified prior to unblinding study drug.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Potential subjects must meet the following criteria at the screening visit to enter this study:
- •male or female, in otherwise good health, 18 to 65 years of age.
- •history of chronic migraine meeting the diagnostic criteria listed in the International Classification of Headache Disorders (ICHD-III beta version, 2013), as follows:
- •a. History of frequent headaches suggestive of chronic migraine (15 or greater days of qualifying headaches per month) for at least three months prior to screening b. Verification of headache frequency through prospectively collected baseline information during the 28-day run-in phase demonstrating headaches on at least 15 days, with at least 8 days per month fulfilling any ONE of the following; i. Qualify as being a migraine attack ii. Relieved by migraine specific acute medications
- •onset of migraine before age
- •stable pattern of migraine pattern for at least 3 months prior to screening.
- •not currently taking a migraine preventive OR has been taking a stable dose of a preventive for at least 30 days prior to screening and agrees to not start, stop, or change medication and/or dosage during the study period.
- •i. Subjects on migraine preventative should have stable headache pattern ii. Injections of onabotulinumtoxinA are allowable if subject has completed at least 2 injection cycles and agrees to maintain a regular injection cycle for the duration of the study
排除标准
- •Potential subjects meeting any of the following criteria will be excluded from entering this study:
- •unable to understand the study requirements, the informed consent, or complete headache records as required per protocol.
- •pregnant, actively trying to become pregnant, or breast-feeding.
- •history of medication overuse (MO) of opioids, or butalbital, as defined by ICHD-3 beta criteria and/or MO during baseline period.
- •history of substance abuse and/or dependence, in the opinion of the Investigator.
- •unstable neurological condition or a significantly abnormal neurological examination with focal signs or signs of increased intracranial pressure.
研究组 & 干预措施
IONIS-PKKRx (ISIS 546254)
Those randomized to IONIS-PKKRx (ISIS 546254) will receive subcutaneous injections containing 1.00 mL (200mg) weekly for weeks 1-16.
干预措施: IONIS-PKKRx (ISIS 546254) (Drug)
Placebo
Those randomized to placebo will receive subcutaneous injections containing 1.00 mL (200mg) weekly for weeks 1-16.
干预措施: Placebo (Other)
结局指标
主要结局
Migraine Days
时间窗: Comparing baseline to treatment period, up to 16 weeks
Compare the efficacy of ISIS 546254 in the preventive treatment of chronic migraine, measured by the number of monthly migraine days comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.
次要结局
- Headache Days(Comparing baseline to treatment period, up to 16 weeks)
- Count of Migraine Headache Days Requiring Use of Migraine Medication(Comparing baseline to treatment period, up to 16 weeks)
- Migraine Specific Quality of Life (MSQ) Questionnaire Score(Comparing baseline to treatment period, up to 16 weeks)
- Headache Severity(Comparing baseline to treatment period, up to 16 weeks)
- Number of Subjects Reporting a ≥ 50% Reduction in the Number of Migraine Headaches(Comparing baseline to treatment period, up to 16 weeks)
- Subject Global Impress of Change (SGIC) Score(Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks)
- Physician Global Impress of Change (PGIC) Score(Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks)
研究者
Timothy Smith
Principal Investigator
Smith, Timothy R., M.D.