Trial Outcomes & Findings for A Study to Test if Fremanezumab is Effective in Preventing Episodic Migraine in Patients 6 to 17 Years of Age (NCT NCT04458857)
NCT ID: NCT04458857
Last Updated: 2025-06-22
Results Overview
A migraine day was defined as a day with any of the following: A day (0:00 to 23:59) with at least 2 hours of headache with ≥2 migraine symptom(s) or day (0:00 to 23:59) demonstrating a headache treated with migraine medications (e.g., non-steroidal anti-inflammatory drugs \[NSAIDs\], paracetamol etc.), or a headache associated with aura. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in electronic diary (e-diary) for 12-week period) \* 28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA). The full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on primary endpoint. Efficacy analysis was planned to be collected and evaluated combined for both fremanezumab dose treatment groups.
COMPLETED
PHASE3
235 participants
Baseline (Day -28 to Day -1), up to Week 12
2025-06-22
Participant Flow
A total of 411 participants were screened; of which 235 participants were randomized and included in the analysis.
Participant milestones
| Measure |
Placebo
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose A
Participants weighing \<threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Overall Study
STARTED
|
112
|
36
|
87
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
112
|
36
|
87
|
|
Overall Study
COMPLETED
|
106
|
33
|
86
|
|
Overall Study
NOT COMPLETED
|
6
|
3
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose A
Participants weighing \<threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
0
|
|
Overall Study
Withdrawal by parent/guardian
|
0
|
0
|
1
|
|
Overall Study
Non-compliance with study drug
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
4
|
1
|
0
|
Baseline Characteristics
A Study to Test if Fremanezumab is Effective in Preventing Episodic Migraine in Patients 6 to 17 Years of Age
Baseline characteristics by cohort
| Measure |
Placebo
n=112 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose A
n=36 Participants
Participants weighing \<threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
Total
n=235 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
13.4 years
STANDARD_DEVIATION 2.99 • n=93 Participants
|
11.0 years
STANDARD_DEVIATION 2.27 • n=4 Participants
|
14.2 years
STANDARD_DEVIATION 2.34 • n=27 Participants
|
13.3 years
STANDARD_DEVIATION 2.86 • n=483 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
50 Participants
n=27 Participants
|
130 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
37 Participants
n=27 Participants
|
105 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
21 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
102 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
75 Participants
n=27 Participants
|
208 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
84 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
68 Participants
n=27 Participants
|
180 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
24 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
44 Participants
n=483 Participants
|
|
Number of Migraine Days Per Month
|
7.5 migraine days per month
STANDARD_DEVIATION 2.84 • n=93 Participants
|
7.6 migraine days per month
STANDARD_DEVIATION 2.92 • n=4 Participants
|
7.9 migraine days per month
STANDARD_DEVIATION 3.21 • n=27 Participants
|
7.7 migraine days per month
STANDARD_DEVIATION 2.99 • n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day -28 to Day -1), up to Week 12Population: The full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
A migraine day was defined as a day with any of the following: A day (0:00 to 23:59) with at least 2 hours of headache with ≥2 migraine symptom(s) or day (0:00 to 23:59) demonstrating a headache treated with migraine medications (e.g., non-steroidal anti-inflammatory drugs \[NSAIDs\], paracetamol etc.), or a headache associated with aura. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in electronic diary (e-diary) for 12-week period) \* 28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA). The full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on primary endpoint. Efficacy analysis was planned to be collected and evaluated combined for both fremanezumab dose treatment groups.
Outcome measures
| Measure |
Placebo
n=111 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=123 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Mean Change From Baseline in Monthly Average Number of Migraine Days During 12-Week Period After the First Dose of Study Drug
|
-1.4 days/month
Standard Error 0.39
|
-2.5 days/month
Standard Error 0.38
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Month 3Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Placebo
n=112 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=36 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
55 Participants
|
20 Participants
|
48 Participants
|
SECONDARY outcome
Timeframe: Baseline to last assessment (up to Month 3)Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Placebo
n=112 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=36 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Normal/Normal
|
92 Participants
|
32 Participants
|
74 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Abnormal NCS/Normal
|
13 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Abnormal CS/Normal
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Normal/Abnormal NCS
|
2 Participants
|
2 Participants
|
6 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Abnormal NCS/Abnormal NCS
|
4 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Abnormal CS/Abnormal NCS
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Normal/Abnormal CS
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Abnormal NCS/Abnormal CS
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Abnormal CS/Abnormal CS
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)
Missing
|
1 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to last assessment (up to Month 3)Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Placebo
n=112 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=36 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist)
Normal/Normal
|
88 Participants
|
29 Participants
|
72 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist)
Abnormal/Normal
|
14 Participants
|
0 Participants
|
5 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist)
Normal/Abnormal
|
2 Participants
|
4 Participants
|
4 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist)
Abnormal/Abnormal
|
6 Participants
|
2 Participants
|
6 Participants
|
|
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist)
Missing
|
2 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 3Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants with at least one Baseline and post-baseline vital sign assessment.
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; Systolic blood pressure ≤85 millimeters of mercury (mmHg) and decrease from baseline of ≥20 mmHg; Diastolic blood pressure ≥100 mmHg and increase from baseline of ≥15 mmHg; Respiratory rate \<15 breaths/minute. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Placebo
n=112 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=35 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants With Any One or More Potentially Clinically Significant Vital Signs Abnormalities
|
14 Participants
|
3 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 3Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' and 'Number analyzed'= participants with at least one Baseline and post-baseline assessment of the specified laboratory parameters.
Serum chemistry tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≥2\*upper limit of normal (ULN); and bilirubin ≥34.2 micromole/liter (umol/L). Hematology tests with potentially clinically significant abnormal findings included: hemoglobin ≤100 grams (g)/L, leukocytes ≤3\*10\^9 cells/L, neutrophils ≤1\*10\^9 cells/L, eosinophils/leukocytes ≥10%, and platelets ≥700\*10\^9 cells/L or ≤75\*10\^9 cells/L. Coagulation parameter test with potentially clinically significant abnormal findings included: prothrombin international normalized ratio (INR) \>1.5. Urinalysis laboratory tests with potentially clinically significant abnormal findings included: urine protein ≥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.
Outcome measures
| Measure |
Placebo
n=111 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=35 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results
With at least 1 serum chemistry abnormality
|
2 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results
With at least 1 hematology abnormality
|
6 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results
With at least 1 coagulation abnormality
|
3 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results
With at least 1 urinalysis abnormality
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 3Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants with at least one Baseline and post-baseline physical examination.
A complete physical examination included the following organ systems: general appearance; head, eyes, ears, nose, and throat (HEENT); chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. Only the organ systems with abnormal physical findings in at least one treatment group have been reported. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Placebo
n=109 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=34 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator
General Appearance
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator
HEENT
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator
Musculoskeletal
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator
Skin
|
5 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator
Neurological
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator
Extremities/Back
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline and Month 3Population: The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants with both Baseline and Month 3 assessment.
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.
Outcome measures
| Measure |
Placebo
n=105 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=33 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=86 Participants
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Month 3
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1), up to Week 12Population: The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the participant reported either of the following: A day with headache pain that lasted ≥2 hours with a peak severity of at least moderate severity or a day where the participant used acute medication (triptans, ergots, NSAIDs or paracetamol) to treat a headache of any severity or duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) \* 28. LS mean was calculated using ANCOVA.
Outcome measures
| Measure |
Placebo
n=111 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=123 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Mean Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During 12-Week Period After the First Dose of Study Drug
|
-1.5 days/month
Standard Error 0.42
|
-2.6 days/month
Standard Error 0.40
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1) up to Week 12Population: The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache that was accompanied by ≥1 migraine symptom(s) or a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine specific medications (NSAIDs, paracetamol or triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) \* 28.
Outcome measures
| Measure |
Placebo
n=111 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=123 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of Study Drug
|
30 Participants
|
58 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1), up to Week 12Population: The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
Participants recorded any headache medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken each day in their electronic headache diary device. Acute headache medication included triptans and ergot compounds, NSAIDs or paracetamol. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) \* 28. LS mean was calculated using ANCOVA.
Outcome measures
| Measure |
Placebo
n=111 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=123 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Mean Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During 12-Week Period After the First Dose of Study Drug
|
-1.0 days/month
Standard Error 0.30
|
-2.1 days/month
Standard Error 0.29
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
The PedMIDAS is a scale developed to assess headache-related disability which can be self-administered by the participant or administered by a caregiver. It has been validated in participants aged 4 to 18 years and includes 3 subscales: the impact of headache on school performance (range of scores 0-92), disability at home (range of scores 0-92), social/sport functioning (range of scores 0-92). The subscales are added to get the total score with a range 0 to 276. The total score was used for grading of disability, with 4 score categories of 0 to 10, 11 to 30, 31 to 50, and 51-276 interpreted as disability grades 1 (little or no disability), 2 (mild disability), 3 (moderate disability), and 4 (severe disability), respectively. Higher total scores indicated severe disability. LS mean was calculated using ANCOVA. The change from baseline score is reported with a range of -276 to 276 with higher scores indicating more severe disability.
Outcome measures
| Measure |
Placebo
n=111 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=123 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Mean Change From Baseline in Migraine-related Disability Score at Week 12, as Measured by the Pediatric Migraine Disability Assessment (PedMIDAS) Questionnaire
|
-15.3 units on a scale
Standard Error 3.37
|
-21.6 units on a scale
Standard Error 3.29
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
PedsQL 4.0 is a brief 23-item health-related quality of life (QoL) instrument that evaluates QoL in 4 areas of functioning: physical, emotional, social, and school functioning. For child and adolescent self-report (8 - 18 years) and parent report forms, respondents used a 5-point Likert scale to rate item severity (0=never a problem;1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem). For younger children (5 - 7 years), a simplified 3-point Likert scale, anchored with a happy and a sad face, was used (0=not at all a problem; 2=sometimes a problem; 4=a lot of a problem). PedsQL yields a total QoL score and 2 summary scores: Physical Health Summary Score and Psychosocial Health Summary Score. To obtain scores, items were reverse scored, transformed to a 0 through 100 scale (0=100, 1=75, 2=50, 3=25, 4=0), and averaged; total scores near 0 indicated lower QoL, while scores approaching 100 indicated higher QoL. LS mean was calculated using ANCOVA.
Outcome measures
| Measure |
Placebo
n=111 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=123 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire
Child-Psychosocial Health Summary Score
|
5.3 units on a scale
Standard Error 1.38
|
4.7 units on a scale
Standard Error 1.35
|
—
|
|
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire
Child-Physical Health Summary Score
|
8.3 units on a scale
Standard Error 1.61
|
7.8 units on a scale
Standard Error 1.57
|
—
|
|
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire
Child-Total Scale Score
|
6.2 units on a scale
Standard Error 1.37
|
5.7 units on a scale
Standard Error 1.33
|
—
|
|
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire
Parent-Physical Health Summary Score
|
7.3 units on a scale
Standard Error 2.69
|
7.3 units on a scale
Standard Error 2.35
|
—
|
|
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire
Parent-Psychosocial Health Summary Score
|
6.8 units on a scale
Standard Error 2.28
|
4.3 units on a scale
Standard Error 1.96
|
—
|
|
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire
Parent-Total Scale Score
|
7.2 units on a scale
Standard Error 2.28
|
5.2 units on a scale
Standard Error 1.97
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Month 3Population: The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Here, 'Overall number of participants analyzed' = Participants who had Baseline and at least 1 postbaseline ADA assessment.
Number of participants who developed ADAs were reported.
Outcome measures
| Measure |
Placebo
n=35 Participants
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab
n=87 Participants
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Number of Participants Developing Anti-drug Antibodies (ADAs) Throughout the Study
|
1 Participants
|
1 Participants
|
—
|
Adverse Events
Placebo
Fremanezumab Dose A
Fremanezumab Dose B
Serious adverse events
| Measure |
Placebo
n=112 participants at risk
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose A
n=36 participants at risk
Participants weighing \<threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 participants at risk
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Immune thrombocytopenia
|
0.89%
1/112 • Number of events 1 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/36 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Hepatitis infectious mononucleosis
|
0.00%
0/112 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/36 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
1.1%
1/87 • Number of events 1 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Hemiparesis
|
0.89%
1/112 • Number of events 3 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/36 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Migraine
|
0.89%
1/112 • Number of events 1 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
2.8%
1/36 • Number of events 1 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Placebo
n=112 participants at risk
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose A
n=36 participants at risk
Participants weighing \<threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57).
|
Fremanezumab Dose B
n=87 participants at risk
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57).
|
|---|---|---|---|
|
General disorders
Injection site erythema
|
5.4%
6/112 • Number of events 9 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
2.8%
1/36 • Number of events 2 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
12.6%
11/87 • Number of events 18 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
General disorders
Injection site pain
|
5.4%
6/112 • Number of events 10 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/36 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
6.9%
6/87 • Number of events 9 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
General disorders
Injection site swelling
|
0.89%
1/112 • Number of events 1 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
2.8%
1/36 • Number of events 1 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
5.7%
5/87 • Number of events 6 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
General disorders
Vaccination site pain
|
0.89%
1/112 • Number of events 1 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
5.6%
2/36 • Number of events 2 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Infections and infestations
COVID-19
|
5.4%
6/112 • Number of events 6 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
5.6%
2/36 • Number of events 2 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
5.7%
5/87 • Number of events 5 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
8/112 • Number of events 10 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
8.3%
3/36 • Number of events 4 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
9.2%
8/87 • Number of events 10 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
4.5%
5/112 • Number of events 6 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
5.6%
2/36 • Number of events 2 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
4.6%
4/87 • Number of events 5 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/112 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/36 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
5.7%
5/87 • Number of events 5 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
1.8%
2/112 • Number of events 3 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
5.6%
2/36 • Number of events 3 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Baseline up to Month 3
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER