An Efficacy and Safety Study of Fremanezumab in Adults With Migraine (FOCUS)

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 838
• Phase: Phase 3

Expanded Access

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

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • Teva Investigational Site 37092
  • Brussels, Belgium, 1090
    • Teva Investigational Site 37089
  • Hasselt, Belgium, 3500
    • Teva Investigational Site 37091
  • Liege, Belgium, 4000
    • Teva Investigational Site 37090
• Czechia
  • Brno, Czechia, 602 00
    • Teva Investigational Site 54162
  • Ostrava, Czechia, 70200
    • Teva Investigational Site 54159
  • Ostrava-Moravska, Czechia, 702 00
    • Teva Investigational Site 54165
  • Pardubice, Czechia, 53002
    • Teva Investigational Site 54158
  • Prague, Czechia, 100 00
    • Teva Investigational Site 54163
  • Prague 4, Czechia, 140 59
    • Teva Investigational Site 54164
  • Praha 10, Czechia, 160 00
    • Teva Investigational Site 54160
  • Praha 3, Czechia, 130 00
    • Teva Investigational Site 54161
  • Praha 8, Czechia, 186 00
    • Teva Investigational Site 54166
  • Rychnov nad Kneznou, Czechia, 51601
    • Teva Investigational Site 54157
• Denmark
  • Aalborg, Denmark, 9000
    • Teva Investigational Site 39051
  • Arhus, Denmark, 8000
    • Teva Investigational Site 39049
  • Ballerup, Denmark, 2750
    • Teva Investigational Site 39052
  • Glostrup, Denmark, 2600
    • Teva Investigational Site 39048
  • Vejle, Denmark, 7100
    • Teva Investigational Site 39050
• Finland
  • Helsinki, Finland, 00180
    • Teva Investigational Site 40034
  • Helsinki, Finland, 00930
    • Teva Investigational Site 40035
  • Oulu, Finland, 90100
    • Teva Investigational Site 40036
  • Tampere, Finland, FI-33100
    • Teva Investigational Site 40033
  • Turku, Finland, 20100
    • Teva Investigational Site 40032
  • Turku, Finland, 20520
    • Teva Investigational Site 40037
• France
  • Bron Cedex, France, 69677
    • Teva Investigational Site 35237
  • Lille, France, 59037
    • Teva Investigational Site 35238
  • Marseille, France, 13005
    • Teva Investigational Site 35235
  • Nice, France, 06000
    • Teva Investigational Site 35240
  • Strasbourg, France, 67098
    • Teva Investigational Site 35239
  • Voiron, France, 38500
    • Teva Investigational Site 35236
• Germany
  • Berlin, Germany, 10177
    • Teva Investigational Site 32697
  • Berlin, Germany, D-10435
    • Teva Investigational Site 32690
  • Bochum, Germany, 44787
    • Teva Investigational Site 32694
  • Essen, Germany, 45147
    • Teva Investigational Site 32699
  • Goppingen, Germany, 73033
    • Teva Investigational Site 32692
  • Halle, Germany, 06120
    • Teva Investigational Site 32691
  • Hamburg, Germany, 20251
    • Teva Investigational Site 32698
  • Kiel, Germany, 24149
    • Teva Investigational Site 32700
  • Konigstein im Taunus, Germany, 61462
    • Teva Investigational Site 32695
  • Muenchen, Germany, 81377
    • Teva Investigational Site 32689
  • Rostock, Germany, 18147
    • Teva Investigational Site 32701
  • Ulm, Germany, 89073
    • Teva Investigational Site 32693
• Italy
  • Firenze, Italy, 50134
    • Teva Investigational Site 30199
  • Roma, Italy, 00128
    • Teva Investigational Site 30204
• Netherlands
  • Amsterdam, Netherlands, 1078VV
    • Teva Investigational Site 38126
  • Blaricum, Netherlands, 1261 AN
    • Teva Investigational Site 38127
  • Leiden, Netherlands, 2333 ZA
    • Teva Investigational Site 38124
  • Tilburg, Netherlands, 5042 AD
    • Teva Investigational Site 38125
• Poland
  • Krakow, Poland, 31-209
    • Teva Investigational Site 53420
  • Krakow, Poland, 33-332
    • Teva Investigational Site 53425
  • Lodz, Poland, 90-338
    • Teva Investigational Site 53422
  • Lodz, Poland, 90-368
    • Teva Investigational Site 53424
  • Lublin, Poland, 20-022
    • Teva Investigational Site 53418
  • Poznan, Poland, 60-529
    • Teva Investigational Site 53416
  • Szczecin, Poland, 70-111
    • Teva Investigational Site 53419
  • Warszawa, Poland, 00-909
    • Teva Investigational Site 53417
  • Warszawa, Poland, 04-730
    • Teva Investigational Site 53423
• Spain
  • Barcelona, Spain, 08035
    • Teva Investigational Site 31231
  • Madrid, Spain, 28223
    • Teva Investigational Site 31235
  • Madrid, Spain, 28942
    • Teva Investigational Site 31236
  • Pamplona, Spain, 31008
    • Teva Investigational Site 31226
  • Santander, Spain, 39008
    • Teva Investigational Site 31229
  • Santiago de Compostela, Spain, 15706
    • Teva Investigational Site 31230
  • Sevilla, Spain, 41013
    • Teva Investigational Site 31234
  • Valencia, Spain, 46010
    • Teva Investigational Site 31233
  • Valencia, Spain, 46026
    • Teva Investigational Site 31227
  • Valladolid, Spain, 47003
    • Teva Investigational Site 31225
  • Zaragoza, Spain, 50009
    • Teva Investigational Site 31228
• Sweden
  • Helsingborg, Sweden, 252 20
    • Teva Investigational Site 42050
  • Huddinge, Sweden, 141 86
    • Teva Investigational Site 42049
  • Lund, Sweden, 260 83
    • Teva Investigational Site 42051
  • Stockholm, Sweden, 112 81
    • Teva Investigational Site 42052
  • Stockholm, Sweden, 114 33
    • Teva Investigational Site 42054
• Switzerland
  • Bad Zurzach, Switzerland, 5330
    • Teva Investigational Site 45018
  • Bern, Switzerland, 3010
    • Teva Investigational Site 45016
  • Lugano, Switzerland, 6900
    • Teva Investigational Site 45017
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Teva Investigational Site 34231
  • Hull, United Kingdom, HU3 2JZ
    • Teva Investigational Site 34232
  • London, United Kingdom, SE5 9NT
    • Teva Investigational Site 34233
  • Oxford, United Kingdom, OX3 9DU
    • Teva Investigational Site 34230
  • Salford, United Kingdom, M6 8HD
    • Teva Investigational Site 34235
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Teva Investigational Site 34236
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Teva Investigational Site 14742
  • California
    • Long Beach, California, United States, 90806
      • Teva Investigational Site 14729
    • San Diego, California, United States, 92103
      • Teva Investigational Site 14739
    • Santa Monica, California, United States, 90404
      • Teva Investigational Site 14843
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Teva Investigational Site 14749
  • Florida
    • Maitland, Florida, United States, 32751
      • Teva Investigational Site 14758
    • Orlando, Florida, United States, 32819
      • Teva Investigational Site 14738
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Teva Investigational Site 14760
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Teva Investigational Site 14737
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Teva Investigational Site 14730
    • Evanston, Illinois, United States, 60201
      • Teva Investigational Site 14740
  • Kentucky
    • Louisville, Kentucky, United States, 40223
      • Teva Investigational Site 14735
  • Maryland
    • Pikesville, Maryland, United States, 21208
      • Teva Investigational Site 14747
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Teva Investigational Site 14750
    • Watertown, Massachusetts, United States, 02472
      • Teva Investigational Site 14734
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Teva Investigational Site 14731
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • Teva Investigational Site 14748
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Teva Investigational Site 14746
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Teva Investigational Site 14754
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Teva Investigational Site 14752
  • New York
    • Amherst, New York, United States, 14226
      • Teva Investigational Site 14753
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Teva Investigational Site 14736
    • Greensboro, North Carolina, United States, 27408
      • Teva Investigational Site 14741
    • Raleigh, North Carolina, United States, 27607
      • Teva Investigational Site 14732
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Teva Investigational Site 14761
    • Warwick, Rhode Island, United States, 02886
      • Teva Investigational Site 14756
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Teva Investigational Site 14745
    • Nashville, Tennessee, United States, 37203
      • Teva Investigational Site 14743
  • Texas
    • Austin, Texas, United States, 78731
      • Teva Investigational Site 14733
  • Utah
    • West Jordan, Utah, United States, 84088
      • Teva Investigational Site 14751

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:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Double-blind (DB) period: Participants with CM or EM will receive 3 injections of placebo 1.5 milliliters (mL) SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM will receive fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.	Drug: Fremanezumab; Fremanezumab will be administered per dose and schedule specified in the arm.; Other Names: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered per schedule specified in the arm.
Experimental: Fremanezumab Quarterly; DB period: Participants with CM or EM will receive 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 will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.	Drug: Fremanezumab; Fremanezumab will be administered per dose and schedule specified in the arm.; Other Names: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered per schedule specified in the arm.
Experimental: Fremanezumab Monthly; DB period: Participants with CM will receive 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 will receive 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 will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.	Drug: Fremanezumab; Fremanezumab will be administered per dose and schedule specified in the arm.; Other Names: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered per schedule specified in the arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day -28 to Day -1), up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline (Day -28 to Day-1), up to Week 12
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.	Baseline (Day -28 to Day -1), up to Week 12
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.	Baseline (Day -28 to Day -1), up to Week 4
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	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.	Baseline (Day -28 to Day-1), up to Week 4
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.	Baseline (Day -28 to Day -1), up to Week 12
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.	Baseline (Day -28 to Day -1), up to Week 4
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.	Baseline (Day 0) up to Week 12
OL Period: Number of Participants With 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.	Week 12 up to Week 24
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.	Baseline up to Week 12
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results	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.	Week 12 up to Week 24
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.	Baseline up to Week 12
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results	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.	Week 12 up to Week 24
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.	Baseline up to Week 12
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results	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.	Week 12 up to Week 24
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.	Baseline up to Week 12
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results	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.	Week 12 up to Week 24
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.	Baseline up to Week 12
OL 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 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.	Week 12 up to Week 24
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.	Baseline, Week 12
OL Period: Number of Participants With Shift From Baseline to Week 24 in 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 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.	Baseline, Week 24
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.	Baseline up to Week 12
OL 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.	Week 12 up to Week 24

Collaborators and Investigators

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

Publications and helpful links

General Publications

• McAllister P, Cohen JM, Campos VR, Ning X, Janka L, Barash S. Impact of fremanezumab on disability outcomes in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies. J Headache Pain. 2022 Aug 29;23(1):112. doi: 10.1186/s10194-022-01438-4.
• Diener HC, McAllister P, Jurgens TP, Kessler Y, Ning X, Cohen JM, Campos VR, Barash S, Silberstein SD. Safety and tolerability of fremanezumab in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies. Cephalalgia. 2022 Jul;42(8):769-780. doi: 10.1177/03331024221076485. Epub 2022 Mar 25.
• Lampl C, Rapoport AM, Cohen JM, Barash S, Ramirez Campos V, Seminerio MJ, Ning X, Silberstein SD. Efficacy and quality-of-life improvements with fremanezumab treatment in patients with difficult-to-treat migraine with associated neurological dysfunction. Eur J Neurol. 2022 Jul;29(7):2129-2137. doi: 10.1111/ene.15328. Epub 2022 Mar 29.
• MaassenVanDenBrink A, Terwindt GM, Cohen JM, Barash S, Campos VR, Galic M, Ning X, Karppa M. Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study. J Headache Pain. 2021 Dec 18;22(1):152. doi: 10.1186/s10194-021-01336-1.
• Nahas SJ, Naegel S, Cohen JM, Ning X, Janka L, Campos VR, Krasenbaum LJ, Holle-Lee D, Kudrow D, Lampl C. Efficacy and safety of fremanezumab in clinical trial participants aged >/=60 years with episodic or chronic migraine: pooled results from 3 randomized, double-blind, placebo-controlled phase 3 studies. J Headache Pain. 2021 Nov 24;22(1):141. doi: 10.1186/s10194-021-01351-2. Erratum In: J Headache Pain. 2022 May 17;23(1):57.
• Ashina M, Cohen JM, Galic M, Campos VR, Barash S, Ning X, Kessler Y, Janka L, Diener HC. Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study. J Headache Pain. 2021 Jul 10;22(1):68. doi: 10.1186/s10194-021-01279-7.
• Pazdera L, Cohen JM, Ning X, Campos VR, Yang R, Pozo-Rosich P. Fremanezumab for the Preventive Treatment of Migraine: Subgroup Analysis by Number of Prior Preventive Treatments with Inadequate Response. Cephalalgia. 2021 Sep;41(10):1075-1088. doi: 10.1177/03331024211008401. Epub 2021 May 14.
• Spierings ELH, Karppa M, Ning X, Cohen JM, Campos VR, Yang R, Reuter U. Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial. J Headache Pain. 2021 Apr 16;22(1):26. doi: 10.1186/s10194-021-01232-8.
• Ferrari MD, Diener HC, Ning X, Galic M, Cohen JM, Yang R, Mueller M, Ahn AH, Schwartz YC, Grozinski-Wolff M, Janka L, Ashina M. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet. 2019 Sep 21;394(10203):1030-1040. doi: 10.1016/S0140-6736(19)31946-4. Epub 2019 Aug 16. Erratum In: Lancet. 2019 Oct 29;:

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2017
• Primary Completion (Actual): October 2, 2018
• Study Completion (Actual): May 29, 2019

Study Registration Dates

• First Submitted: October 3, 2017
• First Submitted That Met QC Criteria: October 12, 2017
• First Posted (Actual): October 13, 2017

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 5, 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-30068; 2017-002441-30 (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