Trial Outcomes & Findings for A Study to Test if Fremanezumab is Effective in Preventing Chronic Migraine in Participants 6 to 17 Years of Age (NCT NCT04464707)

NCT ID: NCT04464707

Last Updated: 2025-12-19

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).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 292 participants
• Primary outcome timeframe: Baseline (Day -28 to Day -1), up to Week 12
• Results posted on: 2025-12-19

Participant Flow

A total of 494 participants were screened; of which 292 participants were randomized and included in the analysis. As pre-specified in the Protocol and Statistical Analysis Plan, the primary and secondary efficacy analyses were conducted to compare the placebo and the pooled active arms.

Participant milestones

Measure	Placebo Participants received placebo matched to fremanezumab subcutaneously (SC) for 3 months (Days 1, 29, and 57).	Fremanezumab 120 mg Participants weighing \<threshold weight received fremanezumab 120 milligrams (mg) SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
Overall Study STARTED	143	26	123
Overall Study Received at Least 1 Dose of Study Drug	143	26	123
Overall Study COMPLETED	139	25	120
Overall Study NOT COMPLETED	4	1	3

Reasons for withdrawal

Measure	Placebo Participants received placebo matched to fremanezumab subcutaneously (SC) for 3 months (Days 1, 29, and 57).	Fremanezumab 120 mg Participants weighing \<threshold weight received fremanezumab 120 milligrams (mg) SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
Overall Study Adverse Event	1	0	0
Overall Study Withdrawal by Subject	0	0	2
Overall Study Withdrawal by Parent/Guardian	0	1	0
Overall Study Protocol Deviation	1	0	0
Overall Study Lost to Follow-up	2	0	1

Baseline Characteristics

A Study to Test if Fremanezumab is Effective in Preventing Chronic Migraine in Participants 6 to 17 Years of Age

Baseline characteristics by cohort

Measure	Placebo n=143 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 120 mg n=26 Participants Participants weighing \<threshold weight received fremanezumab 120 mg SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).	Total n=292 Participants Total of all reporting groups
Age, Continuous	14.3 years STANDARD_DEVIATION 2.46 • n=8 Participants	11.7 years STANDARD_DEVIATION 2.60 • n=6 Participants	15.2 years STANDARD_DEVIATION 1.75 • n=6 Participants	14.4 years STANDARD_DEVIATION 2.39 • n=9 Participants
Sex: Female, Male Female	102 Participants n=8 Participants	15 Participants n=6 Participants	97 Participants n=6 Participants	214 Participants n=9 Participants
Sex: Female, Male Male	41 Participants n=8 Participants	11 Participants n=6 Participants	26 Participants n=6 Participants	78 Participants n=9 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=8 Participants	2 Participants n=6 Participants	12 Participants n=6 Participants	22 Participants n=9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	135 Participants n=8 Participants	23 Participants n=6 Participants	109 Participants n=6 Participants	267 Participants n=9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=8 Participants	1 Participants n=6 Participants	2 Participants n=6 Participants	3 Participants n=9 Participants
Race/Ethnicity, Customized Race · White	123 Participants n=8 Participants	21 Participants n=6 Participants	101 Participants n=6 Participants	245 Participants n=9 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=8 Participants	0 Participants n=6 Participants	4 Participants n=6 Participants	8 Participants n=9 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=8 Participants	0 Participants n=6 Participants	2 Participants n=6 Participants	2 Participants n=9 Participants
Race/Ethnicity, Customized Race · Other	2 Participants n=8 Participants	1 Participants n=6 Participants	2 Participants n=6 Participants	5 Participants n=9 Participants
Race/Ethnicity, Customized Race · Missing	14 Participants n=8 Participants	4 Participants n=6 Participants	14 Participants n=6 Participants	32 Participants n=9 Participants
Number of Migraine Days Per Month	15.7 migraine days per month STANDARD_DEVIATION 5.02 • n=8 Participants	12.3 migraine days per month STANDARD_DEVIATION 6.42 • n=6 Participants	14.4 migraine days per month STANDARD_DEVIATION 5.32 • n=6 Participants	14.8 migraine days per month STANDARD_DEVIATION 5.35 • n=9 Participants

PRIMARY outcome

Timeframe: Baseline (Day -28 to Day -1), up to Week 12

Population: 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. The intent-to-treat (ITT) analysis set included all randomized participants. As pre-specified in the Protocol and Statistical Analysis Plan, the primary and secondary efficacy analyses were conducted to compare the placebo and the pooled active arms.

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).

Outcome measures

Measure	Placebo n=140 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=149 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	-3.7 days/month Standard Error 0.78	-3.8 days/month Standard Error 0.80	—

SECONDARY outcome

Timeframe: Baseline up to Month 3

Population: 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=143 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=26 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	77 Participants	16 Participants	71 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=143 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=26 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	127 Participants	25 Participants	110 Participants
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator) Abnormal NCS/Normal	5 Participants	0 Participants	3 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	7 Participants	0 Participants	7 Participants
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator) Abnormal NCS/Abnormal NCS	3 Participants	1 Participants	2 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	0 Participants	1 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=143 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=26 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	118 Participants	22 Participants	109 Participants
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist) Abnormal/Normal	7 Participants	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist) Normal/Abnormal	12 Participants	1 Participants	6 Participants
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist) Abnormal/Abnormal	5 Participants	3 Participants	5 Participants
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist) Missing	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to Month 3

Population: 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; or ≤60 bpm and decrease from baseline of ≥15 bpm; and 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=142 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=26 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=122 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
Number of Participants With Any One or More Potentially Clinically Significant Vital Sign Abnormalities	5 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Month 3

Population: 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, and eosinophils/leukocytes ≥10%. 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=142 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=26 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=122 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	6 Participants	1 Participants	5 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	5 Participants
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results With at least 1 coagulation abnormality	1 Participants	0 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results With at least 1 urinalysis abnormality	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Month 3

Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.

A complete physical examination included the following organ systems: general appearance; head, eyes, ears, nose, and throat (HEENT); chest and lungs; cardiovascular; abdomen; musculoskeletal; skin; lymph nodes; neurological, and extremities/back. 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=143 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=26 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator	11 Participants	0 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline and Month 3

Population: 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 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=143 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=26 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 Participants Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	2 Participants	0 Participants	1 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 12

Population: 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. As pre-specified in the Protocol and Statistical Analysis Plan, the primary and secondary efficacy analyses were conducted to compare the placebo and the pooled active arms.

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 headache 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=140 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=149 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	-3.8 days/month Standard Error 0.76	-3.1 days/month Standard Error 0.78	—

SECONDARY outcome

Timeframe: Baseline (Day -28 to Day -1) up to Week 12

Population: 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. As pre-specified in the Protocol and Statistical Analysis Plan, the primary and secondary efficacy analyses were conducted to compare the placebo and the pooled active arms.

A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (00:00 to 23:59) demonstrating at least 2 consecutive hours of a headache that was accompanied by ≥1 migraine symptom(s) or a calendar day (00:00 to 23:59) demonstrating a headache of any duration that was treated with acute headache 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. LS mean was calculated using ANCOVA.

Outcome measures

Measure	Placebo n=140 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=149 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	28 Participants	30 Participants	—

SECONDARY outcome

Timeframe: Baseline (Day -28 to Day -1), up to Week 12

Population: 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. As pre-specified in the Protocol and Statistical Analysis Plan, the primary and secondary efficacy analyses were conducted to compare the placebo and the pooled active arms.

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=140 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=149 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	-2.2 days/month Standard Error 0.46	-2.0 days/month Standard Error 0.47	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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. As pre-specified in the Protocol and Statistical Analysis Plan, the primary and secondary efficacy analyses were conducted to compare the placebo and the pooled active arms.

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=140 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=149 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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	-33.5 units on a scale Standard Error 7.97	-26.2 units on a scale Standard Error 8.17	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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. As pre-specified in the Protocol and Statistical Analysis Plan, the primary and secondary efficacy analyses were conducted to compare the placebo and the pooled active arms.

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=140 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=149 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC 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-Physical Health Summary Score	8.0 units on a scale Standard Error 2.11	6.5 units on a scale Standard Error 2.20	—
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	7.7 units on a scale Standard Error 1.36	6.6 units on a scale Standard Error 1.40	—
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	7.6 units on a scale Standard Error 1.43	6.2 units on a scale Standard Error 1.48	—
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	12.0 units on a scale Standard Error 3.43	4.7 units on a scale Standard Error 3.80	—
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	11.6 units on a scale Standard Error 2.40	4.9 units on a scale Standard Error 2.65	—
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	11.7 units on a scale Standard Error 2.47	4.8 units on a scale Standard Error 2.73	—

SECONDARY outcome

Timeframe: Baseline up to Month 3

Population: 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=26 Participants Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab n=121 Participants Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
Number of Participants Developing Anti-drug Antibodies (ADAs) Throughout the Study	1 Participants	0 Participants	—

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 39 other events

Deaths: 0 deaths

Fremanezumab 120 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Fremanezumab 225 mg

Serious events: 4 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=143 participants at risk Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 120 mg n=26 participants at risk Participants weighing \<threshold weight received fremanezumab 120 mg SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 participants at risk Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
Nervous system disorders Migraine	0.70% 1/143 • 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% 0/26 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	2.4% 3/123 • 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.
Nervous system disorders Status migrainosus	0.00% 0/143 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/26 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.81% 1/123 • 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.
Psychiatric disorders Neurosis	0.70% 1/143 • 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% 0/26 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/123 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Immune system disorders Anaphylactic shock	0.70% 1/143 • 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% 0/26 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/123 • 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 Meningitis	0.70% 1/143 • 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% 0/26 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/123 • 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	0.70% 1/143 • 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% 0/26 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/123 • 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=143 participants at risk Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57).	Fremanezumab 120 mg n=26 participants at risk Participants weighing \<threshold weight received fremanezumab 120 mg SC for 3 months (Days 1, 29, and 57).	Fremanezumab 225 mg n=123 participants at risk Participants weighing ≥threshold weight received fremanezumab 225 mg SC for 3 months (Days 1, 29, and 57).
General disorders Injection site erythema	14.0% 20/143 • Number of events 31 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	11.5% 3/26 • 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.	10.6% 13/123 • Number of events 15 • 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	9.8% 14/143 • Number of events 25 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	19.2% 5/26 • Number of events 7 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	9.8% 12/123 • Number of events 14 • 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	10.5% 15/143 • Number of events 20 • Baseline up to Month 3 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	11.5% 3/26 • 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.	8.1% 10/123 • Number of events 14 • 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	2.8% 4/143 • 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.	7.7% 2/26 • 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.	1.6% 2/123 • 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.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 888-483-8279

Email: USMedInfo@tevapharm.com

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