An Efficacy and Safety Study of Fremanezumab in Adults With Migraine

A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study With an Open-Label Period to Evaluate the Efficacy and Safety of Fremanezumab for the Prophylactic Treatment of Migraine in Patients With Inadequate Response to Prior Preventive Treatments

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03308968

Acronym

FOCUS

Enrollment

838

Registered

2017-10-13

Start date

2017-10-13

Completion date

2019-05-29

Last updated

2021-11-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine Prophylaxis

Brief summary

The purpose of this study is to evaluate the efficacy, safety, and tolerability of monthly and quarterly subcutaneous (sc) injections of fremanezumab compared with sc injections of placebo in participants with chronic migraine (CM) or episodic migraine (EM) who have responded inadequately to 2 to 4 classes of prior preventive treatments. Approximately equal numbers of participants from each subgroup (CM and EM) are randomized in blinded-fashion 1:1:1 into one of 3 treatments for the subgroup - 2 active treatments and 1 placebo treatment- consisting of monthly injections for 3 months (up to Week 12). Then all participants continue into an open-label extension of 3 months (up to Week 24) during which everyone is administered sc injections of fremanezumab.

Interventions

DRUGFremanezumab

Fremanezumab will be administered per dose and schedule specified in the arm.

DRUGPlacebo

Placebo matching to fremanezumab will be administered per schedule specified in the arm.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* The participant has a diagnosis of migraine with onset at ≤50 years of age. * Body weight ≥45 kilograms. * The participant has a history of migraine for ≥12 months prior to screening. * Women of childbearing potential (WOCBP) whose male partners are potentially fertile (that is; no vasectomy) must use highly effective birth control methods for the duration of the study and the follow-up period and for 6.0 months after discontinuation of investigational medicinal product (IMP) * Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically \[that is; vasectomy\] or congenitally sterile) and their female partners are of childbearing potential, must use, together with their female partners, acceptable birth control methods for the duration of the study and for 6.0 months after discontinuation of the investigational medicinal product (IMP). * Additional criteria apply, please contact the investigator for more information.

Exclusion criteria

* At the time of screening visit, participant is receiving any preventive migraine medications, regardless of the medical indication for more than 5 days and expects to continue with these medications. * Participant has received onabotulinumtoxinA for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 3 months before screening visit. * The participant has used an intervention/device (for example; scheduled nerve blocks and transcranial magnetic stimulation) for migraine during the 2 months prior to screening. * The participant uses triptans/ergots as preventive therapies for migraine. * Participant uses non-steroidal anti-inflammatory drugs (NSAIDs) as preventive therapy for migraine on nearly daily basis for other indications. Note: Low dose aspirin (for example; 81 mg) used for cardiovascular disease prevention is allowed. * Additional criteria apply, please contact the investigator for more information.

Design outcomes

Primary

Measure	Time frame	Description
DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	Baseline (Day -28 to Day -1), up to Week 12	A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28. Change was calculated as post-baseline value - baseline value.

Secondary

Measure	Time frame	Description
DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab	Baseline (Day -28 to Day -1), up to Week 12	A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\*migraine classification as fixed effects and baseline number of headache days of at least moderate severity and years since onset of migraine as covariates.
DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	Baseline (Day -28 to Day -1), up to Week 4	A migraine day was defined as when at least 1 of following occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day demonstrating a headache of any duration that was treated with migraine-specific medications. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\28. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates.
DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	Baseline (Day -28 to Day-1), up to Week 4	A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28.
DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab	Baseline (Day -28 to Day -1), up to Week 12	Baseline data and the mean change from baseline in the monthly average number of days of use of any acute headache medications during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates.
DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab	Baseline (Day -28 to Day -1), up to Week 4	A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\*migraine classification as fixed effects, and baseline number of headache days of at least moderate severity and years since onset of migraines as covariates.
DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs	Baseline (Day 0) up to Week 12	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs 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. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
OL Period: Number of Participants With AEs and Who Did Not Complete the Study Due to AEs	Week 12 up to Week 24	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs 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. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	Baseline up to Week 12	Criteria for potentially clinically significant abnormal serum chemistry values included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and lactate dehydrogenase (LDH) (units/liter \[U/L\]): greater than or equal to (≥) 3\*upper limit of normal (ULN); Blood Urea Nitrogen (BUN): ≥10.71 millimoles/liter (mmol/L); creatinine: ≥177 micromoles/liter (µmol/L); bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	Week 12 up to Week 24	Criteria for potentially clinically significant abnormal serum chemistry values included: ALT, AST, ALP, GGT, and LDH (U/L): ≥3\*ULN; BUN: ≥10.71 mmol/L; creatinine: ≥177 µmol/L; bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results	Baseline up to Week 12	Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: less than (\<) 115 grams/liter (g/L) (in men) or less than or equal to (≤) 95 g/L (in women), hematocrit: \<0.37 L/L (in men) or \<0.32 L/L (in women), leukocytes: ≥20\10\^9/L or ≤3\10\^9/L, eosinophils: \>=10%, platelets: ≥700\10\^9/L or ≤75\10\^9/L, and absolute neutrophil count (ANC): ≤1\*10\^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	Baseline (Day -28 to Day-1), up to Week 12	A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28.
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results	Baseline up to Week 12	Criteria for potentially clinically significant abnormal coagulation values included: prothrombin international normalized ratio (INR): greater than (\>) 1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results	Week 12 up to Week 24	Criteria for potentially clinically significant abnormal coagulation values included: prothrombin INR: \>1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results	Baseline up to Week 12	Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (milligrams/deciliter \[mg/dL\]): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥2 unit increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results	Week 12 up to Week 24	Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (mg/dL): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥2 unit increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values	Baseline up to Week 12	Criteria for potentially clinically significant abnormal vital signs values included: pulse rate: ≤50 beats/minute (bpm) and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure: ≤90 millimeters of mercury (mmHg) and decrease of ≥20 mmHg, or ≥180 mmHg and increase of ≥20 mmHg; diastolic blood pressure: ≤50 mmHg and decrease of ≥15 mmHg or ≥105 mmHg and increase of ≥15 mmHg; respiratory rate: \<10 breaths/minute; and body temperature ≥38.3 degrees celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values	Week 12 up to Week 24	Criteria for potentially clinically significant abnormal vital signs values included: pulse rate: ≤50 bpm and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure: ≤90 mmHg and decrease of ≥20 mmHg, or ≥180 mmHg and increase of ≥20 mmHg; diastolic blood pressure: ≤50 mmHg and decrease of ≥15 mmHg or ≥105 mmHg and increase of ≥15 mmHg; respiratory rate: \<10 breaths/minute; and body temperature ≥38.3 degrees celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Baseline, Week 12	ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - Week 12 value. Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
OL Period: Number of Participants With Shift From Baseline to Week 24 in ECG Parameters	Baseline, Week 24	ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - Week 24 value. Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events	Baseline up to Week 12	Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc.
OL Period: Number of Participants Who Received Concomitant Medications for Adverse Events	Week 12 up to Week 24	Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc.
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results	Week 12 up to Week 24	Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: \<115 g/L (in men) or ≤95 g/L (in women), hematocrit: \<0.37 L/L (in men) or \<0.32 L/L (in women), leukocytes: ≥20\10\^9/L or ≤3\10\^9/L, eosinophils: \>=10%, platelets: ≥700\10\^9/L or ≤75\10\^9/L, and ANC: ≤1\*10\^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Countries

Belgium, Czechia, Denmark, Finland, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States

Participant flow

Pre-assignment details

A total of 838 participants were randomized in a 1:1:1 ratio to placebo, fremanezumab quarterly, or fremanezumab monthly treatment groups.

Participants by arm

Arm	Count
Placebo DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. OL period: Participants with CM or EM received fremanezumab (TEV-48125) 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.	279
Fremanezumab Quarterly DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.	276
Fremanezumab Monthly DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.	283
Total	838

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Double-Blind Period (12 Weeks)	Adverse Event	3	1	4
Double-Blind Period (12 Weeks)	Lack of Efficacy	1	1	0
Double-Blind Period (12 Weeks)	Lost to Follow-up	1	0	0
Double-Blind Period (12 Weeks)	Non-compliance to study procedures	1	1	0
Double-Blind Period (12 Weeks)	Other than specified	1	0	2
Double-Blind Period (12 Weeks)	Protocol Violation	6	0	2
Double-Blind Period (12 Weeks)	Withdrawal by Subject	2	2	3
Open-Label Period (12 Weeks)	Adverse Event	4	1	1
Open-Label Period (12 Weeks)	Lack of Efficacy	1	2	0
Open-Label Period (12 Weeks)	Lost to Follow-up	0	1	1
Open-Label Period (12 Weeks)	Non-compliance to study procedures	0	0	1
Open-Label Period (12 Weeks)	Other than specified	1	2	1
Open-Label Period (12 Weeks)	Protocol Violation	0	1	1
Open-Label Period (12 Weeks)	Withdrawal by Subject	5	5	7

Baseline characteristics

Characteristic	Total	Fremanezumab Monthly	Fremanezumab Quarterly	Placebo
Age, Continuous	46.2 years STANDARD_DEVIATION 11.04	45.9 years STANDARD_DEVIATION 11.05	45.8 years STANDARD_DEVIATION 10.97	46.8 years STANDARD_DEVIATION 11.1
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants	7 Participants	6 Participants	11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	779 Participants	264 Participants	260 Participants	255 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	35 Participants	12 Participants	10 Participants	13 Participants
Number of Headache Days of at Least Moderate Severity During the 28 Day Baseline Period	12.6 days STANDARD_DEVIATION 5.85	12.7 days STANDARD_DEVIATION 5.82	12.4 days STANDARD_DEVIATION 5.84	12.8 days STANDARD_DEVIATION 5.92
Number of Migraine Days During the 28 Day Baseline Period	14.2 days STANDARD_DEVIATION 5.77	14.1 days STANDARD_DEVIATION 5.58	14.1 days STANDARD_DEVIATION 5.61	14.3 days STANDARD_DEVIATION 6.12
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	4 Participants	3 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Black or African American	8 Participants	4 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other	4 Participants	1 Participants	2 Participants	1 Participants
Race/Ethnicity, Customized Unknown or Not Reported	35 Participants	12 Participants	10 Participants	13 Participants
Race/Ethnicity, Customized White	786 Participants	262 Participants	262 Participants	262 Participants
Sex: Female, Male Female	700 Participants	238 Participants	229 Participants	233 Participants
Sex: Female, Male Male	138 Participants	45 Participants	47 Participants	46 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 277	0 / 276	0 / 285
other Total, other adverse events	88 / 277	90 / 276	81 / 285
serious Total, serious adverse events	13 / 277	10 / 276	11 / 285

Outcome results

Primary

DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab

A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28. Change was calculated as post-baseline value - baseline value.

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

Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	-0.6 days/month	Standard Error 0.34
Fremanezumab Quarterly	DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	-3.7 days/month	Standard Error 0.34
Fremanezumab Monthly	DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	-4.1 days/month	Standard Error 0.34

Comparison: Analysis was performed using analysis of covariance (ANCOVA) method with treatment, sex, region, special group of treatment failure (yes or no), migraine classification (that is; CM or EM), and treatment-by-migraine classification interaction as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. The stratification factors (as randomized) were used in the model.p-value: <0.000195% CI: [-3.84, -2.42]ANCOVA

Comparison: Analysis was performed using ANCOVA method with treatment, sex, region, special group of treatment failure (yes or no), migraine classification (that is; CM or EM), and treatment-by-migraine classification interaction as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. The stratification factors (as randomized) were used in the model.p-value: <0.000195% CI: [-4.19, -2.78]ANCOVA

Secondary

DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab

Baseline data and the mean change from baseline in the monthly average number of days of use of any acute headache medications during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates.

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

Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab	-0.6 days/month	Standard Error 0.32
Fremanezumab Quarterly	DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab	-3.7 days/month	Standard Error 0.32
Fremanezumab Monthly	DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab	-3.9 days/month	Standard Error 0.32

Secondary

DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab

A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\*migraine classification as fixed effects and baseline number of headache days of at least moderate severity and years since onset of migraine as covariates.

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

Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab	-0.6 days/month	Standard Error 0.33
Fremanezumab Quarterly	DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab	-3.9 days/month	Standard Error 0.34
Fremanezumab Monthly	DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab	-4.2 days/month	Standard Error 0.34

Secondary

DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab

A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\*migraine classification as fixed effects, and baseline number of headache days of at least moderate severity and years since onset of migraines as covariates.

Time frame: Baseline (Day -28 to Day -1), up to Week 4

Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab	-0.5 days/month	Standard Error 0.34
Fremanezumab Quarterly	DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab	-4.2 days/month	Standard Error 0.35
Fremanezumab Monthly	DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab	-4.5 days/month	Standard Error 0.34

Secondary

DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab

A migraine day was defined as when at least 1 of following occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day demonstrating a headache of any duration that was treated with migraine-specific medications. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment\*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates.

Time frame: Baseline (Day -28 to Day -1), up to Week 4

Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	-0.6 days/month	Standard Error 0.35
Fremanezumab Quarterly	DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	-4.1 days/month	Standard Error 0.35
Fremanezumab Monthly	DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	-4.1 days/month	Standard Error 0.35

Secondary

DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events

Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc.

Time frame: Baseline up to Week 12

Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events	274 Participants
Fremanezumab Quarterly	DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events	269 Participants
Fremanezumab Monthly	DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events	280 Participants

Secondary

DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs 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. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline (Day 0) up to Week 12

Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs	Any AEs	134 Participants
Placebo	DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs	AEs leading to withdrawal from study	3 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs	Any AEs	151 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs	AEs leading to withdrawal from study	1 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs	Any AEs	129 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs	AEs leading to withdrawal from study	4 Participants

Secondary

DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results

Criteria for potentially clinically significant abnormal coagulation values included: prothrombin international normalized ratio (INR): greater than (\>) 1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline up to Week 12

Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results	2 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results	4 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results	4 Participants

Secondary

DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results

Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: less than (\<) 115 grams/liter (g/L) (in men) or less than or equal to (≤) 95 g/L (in women), hematocrit: \<0.37 L/L (in men) or \<0.32 L/L (in women), leukocytes: ≥20\*10\^9/L or ≤3\*10\^9/L, eosinophils: \>=10%, platelets: ≥700\*10\^9/L or ≤75\*10\^9/L, and absolute neutrophil count (ANC): ≤1\*10\^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline up to Week 12

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results	11 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results	12 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results	3 Participants

Secondary

DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results

Criteria for potentially clinically significant abnormal serum chemistry values included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and lactate dehydrogenase (LDH) (units/liter \[U/L\]): greater than or equal to (≥) 3\*upper limit of normal (ULN); Blood Urea Nitrogen (BUN): ≥10.71 millimoles/liter (mmol/L); creatinine: ≥177 micromoles/liter (µmol/L); bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline up to Week 12

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	1 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	3 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	4 Participants

Secondary

DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results

Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (milligrams/deciliter \[mg/dL\]): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥2 unit increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline up to Week 12

Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results	0 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results	0 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results	0 Participants

Secondary

DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values

Criteria for potentially clinically significant abnormal vital signs values included: pulse rate: ≤50 beats/minute (bpm) and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure: ≤90 millimeters of mercury (mmHg) and decrease of ≥20 mmHg, or ≥180 mmHg and increase of ≥20 mmHg; diastolic blood pressure: ≤50 mmHg and decrease of ≥15 mmHg or ≥105 mmHg and increase of ≥15 mmHg; respiratory rate: \<10 breaths/minute; and body temperature ≥38.3 degrees celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline up to Week 12

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values	9 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values	8 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values	8 Participants

Secondary

DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters

ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - Week 12 value. Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline, Week 12

Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' = participants with both baseline and Week 12 ECG findings.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Abnormal CS	0 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Normal	0 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Abnormal CS	0 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Abnormal NCS	21 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Abnormal NCS	0 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Normal	10 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Abnormal CS	0 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Normal	199 Participants
Placebo	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Abnormal NCS	28 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Abnormal NCS	14 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Abnormal CS	0 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Normal	218 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Normal	0 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Abnormal NCS	0 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Abnormal NCS	20 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Abnormal CS	0 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Abnormal CS	0 Participants
Fremanezumab Quarterly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Normal	19 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Abnormal CS	0 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Abnormal CS	0 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Normal	212 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Normal - Abnormal NCS	15 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Abnormal NCS	31 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Normal	12 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal NCS - Abnormal CS	0 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Normal	0 Participants
Fremanezumab Monthly	DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters	Abnormal CS - Abnormal NCS	0 Participants

Secondary

DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab

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

Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.

Arm	Measure	Value (NUMBER)
Placebo	DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	9 percentage of participants
Fremanezumab Quarterly	DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	34 percentage of participants
Fremanezumab Monthly	DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab	34 percentage of participants

Secondary

DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab

Time frame: Baseline (Day -28 to Day-1), up to Week 4

Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.

Arm	Measure	Value (NUMBER)
Placebo	DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	10 percentage of participants
Fremanezumab Quarterly	DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	38 percentage of participants
Fremanezumab Monthly	DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab	36 percentage of participants

Secondary