Efficacy and Safety of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine (HALO)

A Multicenter, Randomized, Double-Blind, Parallel-Group Study Evaluating the Long-Term Safety, Tolerability, and Efficacy of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine

A study to evaluate the long-term safety, tolerability, and efficacy of subcutaneous (SC) administration of TEV-48125 in adult participants with chronic migraine (CM) or episodic migraine (EM). Participants with CM or EM who complete the pivotal efficacy studies of TEV-48125 (TV48125-CNS-30049 [NCT02621931] and TV48125-CNS-30050 [NCT02629861]) and agree to participate in this study; and new participants meeting eligibility criteria (not rolling over from pivotal studies), will be enrolled in this study.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Fremanezumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1890
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T3M 1M4
    • Teva Investigational Site 11120
  • Montreal, Canada, H2W 1V1
    • Teva Investigational Site 11121
  • Sarnia, Canada, N7T 4X3
    • Teva Investigational Site 11123
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Teva Investigational Site 11124
    • Newmarket, Ontario, Canada, L3Y5G8
      • Teva Investigational Site 11122
• Czechia
  • Brno, Czechia, 602 00
    • Teva Investigational Site 54144
  • Kunratice, Czechia, 14800
    • Teva Investigational Site 54141
  • Pardubice, Czechia, 53002
    • Teva Investigational Site 54145
  • Prague 4, Czechia, 140 59
    • Teva Investigational Site 54142
  • Praha, Czechia, 100 00
    • Teva Investigational Site 54143
  • Praha 3, Czechia, 130 00
    • Teva Investigational Site 54146
• Finland
  • Helsinki, Finland, 00930
    • Teva Investigational Site 40017
  • Helsinki, Finland, 00180
    • Teva Investigational Site 40018
  • Turku, Finland, 20100
    • Teva Investigational Site 40016
• Israel
  • Holon, Israel, 58100
    • Teva Investigational Site 80096
  • Jerusalem, Israel, 9112001
    • Teva Investigational Site 80099
  • Nahariya, Israel, 221001
    • Teva Investigational Site 80098
  • Netanya, Israel, 4244916
    • Teva Investigational Site 80097
  • Ramat Gan, Israel, 5265601
    • Teva Investigational Site 80100
  • Tel Aviv, Israel, 6423906
    • Teva Investigational Site 80095
• Japan
  • Chofu-shi, Japan, 182-0006
    • Teva Investigational Site 84072
  • Kagoshima-shi, Japan, 892-0844
    • Teva Investigational Site 84066
  • Kai, Japan, 400-0124
    • Teva Investigational Site 84069
  • Kawasaki, Japan, 211-8588
    • Teva Investigational Site 84073
  • Kyoto, Japan, 600-8811
    • Teva Investigational Site 84067
  • Osaka-shi, Japan, 556-0015
    • Teva Investigational Site 84062
  • Saitama, Japan, 338-8577
    • Teva Investigational Site 84070
  • Sendai-shi, Japan, 982-0014
    • Teva Investigational Site 84061
  • Shinjuku-ku, Japan, 160-8582
    • Teva Investigational Site 84063
  • Shizuoka, Japan, 4200-853
    • Teva Investigational Site 84068
  • Tochigi, Japan, 321-0293
    • Teva Investigational Site 84065
  • Tokyo, Japan, 182-0006
    • Teva Investigational Site 84064
  • Toyonaka, Japan
    • Teva Investigational Site 84071
• Poland
  • Krakow, Poland, 31-523
    • Teva Investigational Site 53364
  • Krakow, Poland, 33-332
    • Teva Investigational Site 53363
  • Lublin, Poland, 20-022
    • Teva Investigational Site 53366
  • Poznan, Poland, 60-529
    • Teva Investigational Site 53365
  • Warsaw, Poland, 04-730
    • Teva Investigational Site 53367
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Teva Investigational Site 50399
  • Kazan, Russian Federation, 420021
    • Teva Investigational Site 50395
  • Moscow, Russian Federation, 121467
    • Teva Investigational Site 50394
  • Moscow, Russian Federation, 129128
    • Teva Investigational Site 50400
  • Nizhniy Novgorod, Russian Federation, 603126
    • Teva Investigational Site 50398
  • Nizhniy Novgorod, Russian Federation, 603137
    • Teva Investigational Site 50396
  • Ufa, Russian Federation, 450007
    • Teva Investigational Site 50397
• Spain
  • Madrid, Spain, 28046
    • Teva Investigational Site 31207
  • Pamplona, Spain, 31008
    • Teva Investigational Site 31208
  • Valladolid, Spain, 47003
    • Teva Investigational Site 31205
  • Zaragoza, Spain, 50009
    • Teva Investigational Site 31206
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Teva Investigational Site 13628
    • Birmingham, Alabama, United States, 35216
      • Teva Investigational Site 13577
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Teva Investigational Site 13606
    • Phoenix, Arizona, United States, 85023
      • Teva Investigational Site 13579
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Teva Investigational Site 13602
  • California
    • Encino, California, United States, 91316
      • Teva Investigational Site 13568
    • Fullerton, California, United States, 92835
      • Teva Investigational Site 13546
    • Long Beach, California, United States, 90806
      • Teva Investigational Site 13540
    • Redlands, California, United States, 92374
      • Teva Investigational Site 13632
    • Redondo Beach, California, United States, 90277
      • Teva Investigational Site 13571
    • San Diego, California, United States, 92103
      • Teva Investigational Site 13573
    • Santa Monica, California, United States, 90404
      • Teva Investigational Site 13538
    • Santa Rosa, California, United States, 95405
      • Teva Investigational Site 13594
    • Walnut Creek, California, United States, 94598
      • Teva Investigational Site 13595
  • Colorado
    • Aurora, Colorado, United States, 80014
      • Teva Investigational Site 13629
    • Boulder, Colorado, United States, 80301
      • Teva Investigational Site 13557
    • Colorado Springs, Colorado, United States, 80918
      • Teva Investigational Site 13593
    • Denver, Colorado, United States, 80210
      • Teva Investigational Site 13633
    • Denver, Colorado, United States, 80239
      • Teva Investigational Site 13612
    • Englewood, Colorado, United States, 80113
      • Teva Investigational Site 13631
  • Connecticut
    • East Hartford, Connecticut, United States, 06118
      • Teva Investigational Site 13563
    • Stamford, Connecticut, United States, 06905
      • Teva Investigational Site 13550
  • Florida
    • Bradenton, Florida, United States, 34201
      • Teva Investigational Site 13635
    • Gainesville, Florida, United States, 32607
      • Teva Investigational Site 13597
    • Hialeah, Florida, United States, 33012
      • Teva Investigational Site 13607
    • Jacksonville, Florida, United States, 32205
      • Teva Investigational Site 13559
    • Ocala, Florida, United States, 34471
      • Teva Investigational Site 13584
    • Orlando, Florida, United States, 32806
      • Teva Investigational Site 13587
    • Palm Beach Gardens, Florida, United States, 33410
      • Teva Investigational Site 13567
    • Pembroke Pines, Florida, United States, 33026
      • Teva Investigational Site 13553
    • Pinellas Park, Florida, United States, 33781
      • Teva Investigational Site 13616
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Teva Investigational Site 13620
    • Atlanta, Georgia, United States, 30342
      • Teva Investigational Site 13537
  • Idaho
    • Boise, Idaho, United States, 83642
      • Teva Investigational Site 13604
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Teva Investigational Site 13585
    • Chicago, Illinois, United States, 60654
      • Teva Investigational Site 13621
    • Evanston, Illinois, United States, 60201
      • Teva Investigational Site 13627
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Teva Investigational Site 13596
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Teva Investigational Site 13617
    • Wichita, Kansas, United States, 67211
      • Teva Investigational Site 13598
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Teva Investigational Site 13566
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Teva Investigational Site 13603
  • Maryland
    • Pikesville, Maryland, United States, 21208
      • Teva Investigational Site 13582
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Teva Investigational Site 13590
    • New Bedford, Massachusetts, United States, 02301
      • Teva Investigational Site 13589
    • Watertown, Massachusetts, United States, 02472
      • Teva Investigational Site 13543
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Teva Investigational Site 13539
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Teva Investigational Site 13542
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Teva Investigational Site 13534
    • Saint Louis, Missouri, United States, 63141
      • Teva Investigational Site 13619
    • Springfield, Missouri, United States, 65807
      • Teva Investigational Site 13536
  • Nebraska
    • Fremont, Nebraska, United States, 68025
      • Teva Investigational Site 13618
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Teva Investigational Site 13605
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Teva Investigational Site 13578
  • New Jersey
    • Martinsville, New Jersey, United States, 08836
      • Teva Investigational Site 13575
    • Princeton, New Jersey, United States, 08540
      • Teva Investigational Site 13622
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Teva Investigational Site 13588
  • New York
    • Amherst, New York, United States, 14226
      • Teva Investigational Site 13576
    • Plainview, New York, United States, 11803
      • Teva Investigational Site 13565
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Teva Investigational Site 13574
    • Greensboro, North Carolina, United States, 27405
      • Teva Investigational Site 13544
    • Raleigh, North Carolina, United States, 27612
      • Teva Investigational Site 13545
  • Ohio
    • Akron, Ohio, United States, 44311
      • Teva Investigational Site 13609
    • Akron, Ohio, United States, 44311
      • Teva Investigational Site 13634
    • Akron, Ohio, United States, 44311
      • Teva Investigational Site 13625
    • Cincinnati, Ohio, United States, 45227
      • Teva Investigational Site 13533
    • Cincinnati, Ohio, United States, 45249
      • Teva Investigational Site 13624
    • Cleveland, Ohio, United States, 44195
      • Teva Investigational Site 13569
    • Columbus, Ohio, United States, 43212
      • Teva Investigational Site 13626
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Teva Investigational Site 13561
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Teva Investigational Site 13601
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • Teva Investigational Site 13591
    • Philadelphia, Pennsylvania, United States, 19107
      • Teva Investigational Site 13554
    • Uniontown, Pennsylvania, United States, 15401
      • Teva Investigational Site 13608
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Teva Investigational Site 13615
    • Mount Pleasant, South Carolina, United States, 29464
      • Teva Investigational Site 13556
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Teva Investigational Site 13560
    • Memphis, Tennessee, United States, 38119
      • Teva Investigational Site 13551
    • Nashville, Tennessee, United States, 37203
      • Teva Investigational Site 13532
    • Nashville, Tennessee, United States, 37203
      • Teva Investigational Site 13552
  • Texas
    • Austin, Texas, United States, 78731
      • Teva Investigational Site 13541
    • Dallas, Texas, United States, 75214
      • Teva Investigational Site 13623
    • Plano, Texas, United States, 75024
      • Teva Investigational Site 13611
    • San Antonio, Texas, United States, 78229
      • Teva Investigational Site 13572
  • Utah
    • Murray, Utah, United States, 84107
      • Teva Investigational Site 13614
    • West Jordan, Utah, United States, 84088
      • Teva Investigational Site 13581
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Teva Investigational Site 13630
  • Washington
    • Seattle, Washington, United States, 98105
      • Teva Investigational Site 13564
    • Seattle, Washington, United States, 98105
      • Teva Investigational Site 13586
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Teva Investigational Site 13600

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Participants Rolling Over from the Pivotal Efficacy Studies:

• Participant must have signed and dated the informed consent document.

• Participant must have completed the pivotal efficacy study without major protocol violations.

  • Additional criteria apply, please contact the investigator for more information.

Participants Not Rolling Over from the Pivotal Efficacy Studies:

• Males or females aged 18 to 70 years, inclusive, with migraine onset at less than or equal to (≤) 50 years of age.
• Participant signed and dated the informed consent document.
• Participant has a history of migraine or clinical judgment suggests a migraine diagnosis.
• Participant fulfills the criteria for EM or CM with prospectively collected baseline information during the 28-day run-in period.
• Body mass index (BMI) of 17.5 to 37.5 kilograms/square meter (kg/m^2) and a total body weight between 45 and 120 kg, inclusive.

• All participants must be of non-childbearing potential.

  1. Participants must simultaneously use 2 forms of highly effective contraception methods.
  2. Participants will remain abstinent throughout the study.
• Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test prior at screening (confirmed by urine dipstick β-HCG pregnancy test at baseline).

• The participant must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period, and to return to the clinic for the follow-up evaluation.

  • Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

Participants Rolling Over from the Pivotal Efficacy Studies:

• Pregnant or nursing females

• Compliance with daily diary entry lower than 75 percent (%) at the last month of the double-blind treatment period of the pivotal efficacy study.

  • Additional criteria apply, please contact the investigator for more information.

Participants Not Rolling Over from the Pivotal Efficacy Studies:

• Clinically significant findings at the discretion of the investigator.
• Evidence or medical history of clinically significant psychiatric issues, including any suicide attempt in the past, or suicidal ideation with a specific plan in the past 2 years.
• History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological [for example; cerebral ischemia], peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events) such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism -Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
• Past or current history of cancer in the past 5 years, except for appropriately treated nonmelanoma skin carcinoma.
• Pregnant or nursing females.
• History of hypersensitivity reactions to injected proteins, including monoclonal antibodies.
• Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study drug administration or 5 half-lives, whichever is longer.
• History of alcohol or drug abuse during the past 2 years, or alcohol or drug dependence during the past 5 years.

• The participant cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons:

  1. mentally or legally incapacitated or unable to give consent for any reason.
  2. in custody due to an administrative or a legal decision, under guardianship, or institutionalized.
  3. unable to be contacted in case of emergency.
  4. has any other condition, which, in the opinion of the investigator, makes the participant inappropriate for inclusion in the study.

• Participant is a study center or sponsor employee who is directly involved in the study or the relative of such an employee.

  • Additional criteria apply, please contact the investigator for more information.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TEV-48125 225 mg Monthly: New/Placebo Rollover Participants; Participants with CM who were randomized to the placebo treatment group or participants who do not rollover from the pivotal efficacy study, will receive fremanezumab 675 milligrams (mg) SC as loading dose (3 injections of fremanezumab 225 mg/1.5 milliliters [mL] on Day 0) followed by 11 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). Participants with EM who were randomized to the placebo treatment group or participants who do not rollover from the pivotal efficacy study, will receive 12 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).	Drug: Fremanezumab; Fremanezumab will be administered as per the dose and schedule specified in the respective arms.; Other Names: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.
Experimental: TEV-48125 225 mg Monthly: Active Rollover Participants; Participants with CM who were randomized to the active treatment group (Fremanezumab 675/225 mg) in the pivotal efficacy study, will receive fremanezumab 675 mg SC as loading dose (3 injections of fremanezumab 225 mg/1.5 mL on Day 0) followed by 11 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). Participants with EM who were randomized to the active treatment group (Fremanezumab 225 mg) in the pivotal efficacy study, will receive 12 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).	Drug: Fremanezumab; Fremanezumab will be administered as per the dose and schedule specified in the respective arms.; Other Names: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.
Experimental: TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants; Participants with CM or EM who were randomized to the placebo treatment group or participants who do not rollover from the pivotal efficacy study, will receive fremanezumab 675 mg SC once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5 mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).	Drug: Fremanezumab; Fremanezumab will be administered as per the dose and schedule specified in the respective arms.; Other Names: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.
Experimental: TEV-48125 675 mg Quarterly: Active Rollover Participants; Participants with CM or EM who were randomized to the active treatment group (Fremanezumab 675 mg) in the pivotal efficacy study, will receive fremanezumab 675 mg SC once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5 mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).	Drug: Fremanezumab; Fremanezumab will be administered as per the dose and schedule specified in the respective arms.; Other Names: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (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.	Baseline (Day 0) up to follow-up visit (Day 533)
Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	Potentially clinically significant abnormal serum chemistry findings included: Blood Urea Nitrogen (BUN): greater than or equal to (>=) 10.71 millimoles/liter (mmol/L), creatinine: >=177 micromoles/liter (µmol/L), bilirubin: >=34.2 µmol/L, Alanine Aminotransferase (ALT) (units/liter [U/L]): >=3*upper limit of normal (ULN) Aspartate Aminotransferase (AST) (U/L): >=3*ULN, and Gamma Glutamyl Transferase (GGT) (U/L): >=3*ULN. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline (Day 0) up to end of treatment (EOT) visit (Day 336)
Number of Participants With Potentially Clinically Significant Abnormal Hematology Results	Potentially clinically significant abnormal hematology findings included: hemoglobin: less than (<) 115 grams/liter (g/L) (in males) or less than or equal to (<=) 95 g/L (in females), hematocrit: <0.37 L/L (in male) or <0.32 L/L (in female), leukocytes: >=20*10^9/L or <=3*10^9/L, eosinophils/leukocytes: >=10%, and platelets: >=700*10^9/L or <=75*10^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline (Day 0) up to EOT visit (Day 336)
Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results	Potentially clinically significant abnormal urinalysis findings included: blood: >=2 unit increase from baseline, urine glucose (milligrams/decilitre [mg/dL]): >=2 unit increase from baseline, ketones (mg/dL): >=2 unit increase from baseline, urine protein (mg/dL): >=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.	Baseline (Day 0) up to EOT visit (Day 336)
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values	Potentially clinically significant abnormal vital signs findings 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 centigrade and change of >=1.1 degrees centigrade. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline (Day 0) up to EOT visit (Day 336)
Number of Participants With Shift From Baseline to Endpoint 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 - endpoint value (last observed post-baseline 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.	Baseline (Day 0), endpoint (Day 336)
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results	Coagulation parameters included: prothrombin time (PT) (seconds), prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT) (seconds). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline (Day 0), endpoint (Day 336)
Number of Participants With Injection Site Reactions	Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from MedDRA version 18.1 were offered without a threshold applied. Injection site reactions included injection site induration, pain, erythema, haemorrhage, pruritus, swelling, bruising, rash, urticaria, warmth, dermatitis, haematoma, inflammation, discolouration, discomfort, hypersensitivity, hypoaesthesia, irritation, oedema, papule, paraesthesia, vesicles and pallor. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline (Day -28 to Day -1), Month 12
Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)	eC-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.	Baseline (Day -28 to Day -1), Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 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 (for CM participants) or at least 2 consecutive hours (for EM participants) 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 (for CM participants) or at least 2 consecutive hours (for EM participants) 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.	Baseline (Day -28 to Day -1), Month 12
Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12	Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of any severity for both CM and EM participants was defined as a calendar day (00:00 to 23:59) where the participant (using the electronic headache diary device) reports: a day with headache pain that lasts at least 4 hours with a peak severity of any severity or; a day when the participant used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. 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.	Baseline (Day -28 to Day -1), Month 12
Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 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 (for CM participants) or at least 2 consecutive hours (for EM participants) 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 (for CM participants) or at least 2 consecutive hours (for EM participants) 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.	Baseline (Day -28 to Day -1), Month 12
Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period	Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of at least moderate severity for both CM and EM participants was defined as a calendar day (00:00 to 23:59) where the participant (using the electronic headache diary device) reports: a day with headache pain that lasts at least 4 hours with a peak severity of at least moderate severity or; a day when the participant used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. 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.	Baseline (Day -28 to Day -1), Month 12

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Publications and helpful links

General Publications

• Goadsby PJ, Silberstein SD, Yeung PP, Cohen JM, Ning X, Yang R, Dodick DW. Long-term safety, tolerability, and efficacy of fremanezumab in migraine: A randomized study. Neurology. 2020 Nov 3;95(18):e2487-e2499. doi: 10.1212/WNL.0000000000010600. Epub 2020 Sep 10.
• Buse DC, Gandhi SK, Cohen JM, Ramirez-Campos V, Cloud B, Yang R, Cowan RP. Improvements across a range of patient-reported domains with fremanezumab treatment: results from a patient survey study. J Headache Pain. 2020 Sep 4;21(1):109. doi: 10.1186/s10194-020-01177-4.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2016
• Primary Completion (Actual): June 6, 2018
• Study Completion (Actual): December 8, 2018

Study Registration Dates

• First Submitted: December 18, 2015
• First Submitted That Met QC Criteria: December 18, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 6, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: TV48125-CNS-30051; 2015-004550-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No