A Multicenter, Open-Label Study Evaluating the Long-Term Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of Fremanezumab for the Preventive Treatment of Episodic and Chronic Migraine in Pediatric Patients 6 to 17 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 499
- 试验地点
- 92
- 主要终点
- Incidence of abnormal physical examination findings
研究概览
简要总结
The primary objective of the study is to evaluate the long-term safety and tolerability of subcutaneous fremanezumab in the preventive treatment of migraine in pediatric participants 6 to 17 years of age (inclusive at enrollment in the pivotal study).
Secondary objectives are to evaluate the efficacy of subcutaneous fremanezumab in pediatric participants with migraine and to evaluate the immunogenicity of fremanezumab and the impact of ADAs on clinical outcomes in pediatric participants exposed to fremanezumab.
The total duration of the study is planned to be up to 84 months.
详细描述
The study population will be composed of 3 subgroups of participants as follows:
- Participants rolling over from the pivotal Phase 3 pediatric efficacy studies (Studies TV48125-CNS-30082 and TV48125-CNS-30083)
- Participants rolling over from the Phase 1 pediatric pharmacokinetic study (Study TV48125-CNS-10141)
- Participants rolling over from the pivotal Phase 3 pediatric efficacy studies (Studies TV48125-CNS-30082 and TV48125-CNS-30083) for safety follow-up and antidrug antibody (ADA) evaluation only
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 or TV48125-CNS-30083):
- •Participants have completed the pivotal efficacy study and, in the opinion of the Investigator or the Sponsor, are able to complete the study in a safe and compliant way.
- •Participants may continue with a stable dose/regimen of the preventive medication they were taking during the pivotal efficacy studies.
- •The participant continues to meet appropriate criteria carried forward from the pivotal efficacy study/
- •The participant has received all recommended age-appropriate vaccines according to local standard of care and schedule.
- •The participant weighs at least 17.0 kg on the day of study enrollment.
- •NOTE: Additional criteria apply; please contact the investigator for more information.
- •Inclusion Criteria for Participants Rolling Over from the Phase 1 Pediatric Pharmacokinetic Study (Study TV48125-CNS-10141):
- •The participant/caregiver has demonstrated compliance with the electronic headache diary during the 28-day baseline period by entry of headache data on a minimum of 21 out of 28 days (approximately 75% diary compliance).
- •The participant has received all recommended age-appropriate vaccines according to local standard of care and schedule.
- •The participant weighs at least 17.0 kg on the day of study enrollment.
- •The participant has a body mass index ranging from the 5th to 120% of the 95th percentile, inclusive, on the day of study enrollment.
- •Not using preventive medications or using no more than 2 preventive medications for migraine or other medical condition, as long as the dose and regimen have been stable for at least 2 months prior to screening (visit 1).
- •NOTE: Additional criteria apply; please contact the investigator for more information.
- •Inclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 and TV48125-CNS-30083) for Safety and antidrug antibody (ADA) Assessment Only:
- •Participants may be included in this study if they sign and date the informed consent document or upon consent of a parent or guardian, if the participant is younger than the age of consent, accompanied by assent of the participant.
排除标准
- •Exclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 or TV48125-CNS-30083):
- •In the judgment of the investigator, the participant has a clinically significant abnormal finding on study entry, including hematology, blood chemistry, coagulation tests, or urinalysis values/findings (abnormal tests may be repeated for confirmation).
- •The participant has a current history of a clinically significant psychiatric condition, at the discretion of the investigator. Any prior history of a suicide attempt, or a history of suicidal ideation with a specific plan within the past 2 years, must be excluded.
- •The participant has an ongoing infection or a known history of human immunodeficiency virus infection, tuberculosis, Lyme disease, or chronic hepatitis B or C, or a known active infection of coronavirus disease 2019 (COVID-19).
- •The participant has a history of hypersensitivity reactions to injected proteins, including mAbs, or a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome, or the participant is concomitantly using lamotrigine.
- •The participant received a live attenuated vaccine (eg, intranasal flu vaccine, and measles, mumps, and rubella vaccine) within the 12-week period prior to screening. Note: If a medical need arises during the study, the participant may receive a live attenuated vaccine.
- •The participant is pregnant or nursing.
- •In the judgment of the investigator, the participant has an abnormal finding on the baseline 12-lead ECG considered clinically significant.
- •The participant has a current or past medical history of hemiplegic migraine.
- •NOTE: Additional criteria apply; please contact the investigator for more information.
- •Exclusion Criteria for Participants Rolling Over from the Phase 1 Pharmacokinetic Study (TV48125-CNS-10141):
- •The participant has any clinically significant cardiovascular (including congenital cardiac anomalies or thromboembolic events), endocrine, gastrointestinal, genitourinary, hematologic, hepatic, immunologic, neurologic, ophthalmic, pulmonary, renal disease, or complications of an infection, at the discretion of the investigator.
- •The participant has a current history of a clinically significant psychiatric condition, any prior history of a suicide attempt, or a history of suicidal ideation with a specific plan within the past 2 years, at the discretion of the investigator.
- •The participant has an ongoing infection or a known history of human immunodeficiency virus infection, tuberculosis, Lyme disease, or chronic hepatitis B or C, or a known active infection of coronavirus disease 2019 (COVID-19).
- •The participant has a history of hypersensitivity reactions to injected proteins, including mAbs, or a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome, or the participant is concomitantly using lamotrigine.
- •The participant received a live attenuated vaccine (eg, intranasal flu vaccine, and measles, mumps, and rubella vaccine) within the 12-week period prior to screening. Note: If a medical need arises during the study, the participant may receive a live attenuated vaccine.
- •The participant is pregnant or nursing.
- •In the judgment of the investigator, the participant has an abnormal finding on the baseline 12-lead ECG considered clinically significant.
- •The participant has a current or past medical history of hemiplegic migraine.
- •NOTE: Additional criteria apply; please contact the investigator for more information.
- •Exclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 and TV48125-CNS-30083) for Safety and antidrug antibody (ADA) Assessment Only: Not Applicable
研究组 & 干预措施
Fremanezumab
The dose of Fremanezumab to be administered will be confirmed or adjusted, as appropriate, based on the participant's weight every 3 months.
干预措施: Fremanezumab (Drug)
结局指标
主要结局
Incidence of abnormal physical examination findings
时间窗: Day 1- Day 393
Incidence of participants with clinically significant changes in laboratory values
时间窗: Day 1 - Day 253
Incidence of abnormal vital signs
时间窗: Day 1 - Day 253
(systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements
Incidence of adverse events
时间窗: Day 1 - Day 393
including local injection site reaction/pain
Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings
时间窗: Day 1 - Day 253
Yes/No suicidality ideation
时间窗: Day 1 - Day 393
Columbia-Suicide Severity Rating Scale (C-SSRS) The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Scale range: Yes or No response to 10 questions, with minimum to maximum range of 0 to 10. Lower score represents better outcomes.
Number of Participants With Adverse Events (AEs)
时间窗: Day 1 up to Day 393
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results
时间窗: Day 1 up to Day 253
Serum chemistry tests with clinically significant abnormal findings included: alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase ≥2\*upper limit of normal (ULN); gamma glutamyl transferase ≥3\* ULN; bilirubin ≥34.2 micromole/liter (umol/L); and urea nitrogen ≥9 umol/L. Hematology tests with clinically significant abnormal findings included: hemoglobin ≤100 grams (g)/L (female) or ≤100 g/L (male), hematocrit \<0.32 L/L (male), leukocytes ≤3\*10\^9 cells/L or ≥20\*10\^9 cells/L, neutrophils ≤1\*10\^9 cells/L, eosinophils/leukocytes ≥10%, and platelets ≤75x10\^9/L. Coagulation parameter test with clinically significant abnormal findings included: prothrombin international normalized ratio (INR) \>1.5. Urinalysis laboratory tests with clinically significant abnormal findings included: urine protein and urine glucose ≥2 units (U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
时间窗: Baseline to last assessment (up to Day 253)
The number of participants with a shift from Baseline (Normal, Abnormal CS \[Clinically Significant\], or Abnormal NCS \[Not Clinically Significant\]) in any of the following ECG parameters is reported by treatment group: Heart rate, PR interval, QRS interval, RR interval, QT interval, QT interval corrected using the Bazett's formula (QTcB), and QT interval corrected using the Fridericia formula (QTcF). Last assessment was defined as the last observed postbaseline interpretation. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist)
时间窗: Baseline to last assessment (up to Day 253)
The number of participants with a shift from Baseline (Normal or Abnormal) in any of the following ECG parameters is reported by treatment group: Heart rate, PR interval, QRS interval, RR interval, QT interval, QTcB, and QTcF. Last assessment was defined as the last observed postbaseline interpretation. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities
时间窗: Day 1 up to Day 253
Potentially clinically significant abnormal vital signs findings included any one of the following: Pulse rate ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm, or ≤50 bpm and decrease from baseline of ≥15 bpm, or ≤60 bpm and decrease from baseline of ≥15 bpm; systolic blood pressure ≤80 millimeters of mercury (mmHg) and decrease of ≥20 mmHg, or ≤85 mmHg and decrease of ≥20 mmHg, or ≥150 mmHg and increase of ≥20 mmHg; diastolic blood pressure ≤37 mmHg and decrease of ≥15 mmHg, or ≤44 mmHg and decrease of ≥15 mmHg, or ≥100 mmHg and increase of ≥15 mmHg, or ≥93 mmHg and increase of ≥15 mmHg; respiratory rate \<15 or \<10 breaths/minute; and body temperature ≥38.3 degrees Celsius and change ≥1.1 degrees Celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Shift From Baseline to Last Assessment in Physical Examination Findings
时间窗: Baseline to last assessment (up to Day 393)
The number of participants with a shift from Baseline (Normal or Abnormal) in any of the following organ systems examination is reported by treatment group: general appearance; head, eyes, ears, nose, and throat (HEENT); chest and lungs; cardiovascular; abdomen; musculoskeletal; skin; lymph nodes; neurological, and extremities/back. Last assessment was defined as the last observed postbaseline interpretation. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Suicidal Ideation or Behavior, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Day 1 up to Day 393
C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent.
次要结局
- Proportion of participants developing antidrug antibodies (ADAs) throughout the study(Day 1 - Day 393)
- Mean change in the number of headache days of at least moderate severity(Day 1 - Day 253)
- Proportion of participants reaching at least 50% reduction in the number of migraine days(Day 1 - Day 253)
- Proportion of participants reaching at least 50% reduction in the number of headache days of at least moderate severity(Day 1 - Day 253)
- Mean change in the number of days of use of any acute headache medications(Day 1 - Day 253)
- Mean change in the number of migraine days(Day 1 - Day 253)
- Mean change in the PedMIDAS questionnaire score(Day 1 - Day 393)
- Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity(Baseline, Months 1, 5, and 9)
- Mean Change From Baseline in the Monthly Average Number of Migraine Days(Baseline, Months 1, 5, and 9)
- Percentage of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Migraine Days(Months 1, 5, and 9)
- Percentage of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity(Months 1, 5, and 9)
- Mean Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medications(Baseline, Months 1, 5, and 9)
- Mean Change From Baseline in Migraine-related Disability Score, as Measured by the Pediatric Migraine Disability Assessment (PedMIDAS) Questionnaire(Baseline, Months 3, 6, 9, and 14)
- Number of Participants Developing Antidrug Antibodies (ADAs) Throughout the Study(Day 1 up to Day 393)