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

• ClinicalTrials.gov Identifier: NCT03308968
• Recruitment Status: Completed
• First Posted: October 13, 2017
• Results First Posted: October 9, 2019
• Last Update Posted: November 9, 2021
• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Information provided by (Responsible Party): Teva Branded Pharmaceutical Products R&D, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Migraine Prophylaxis	Drug: Fremanezumab; Drug: Placebo	Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 838 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 13, 2017
• Actual Primary Completion Date: October 2, 2018
• Actual Study Completion Date: May 29, 2019

Arms and Interventions

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 Name: 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 Name: 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 Name: TEV-48125; Drug: Placebo; Placebo matching to fremanezumab will be administered per schedule specified in the arm.

Outcome Measures

Primary Outcome Measures :

1. DB Period: Change 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 ]
   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 Outcome Measures :

1. 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 ]
   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.
2. 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 [ Time Frame: 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.
3. DB Period: Change 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 ]
   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.
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 [ Time Frame: 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.
5. 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 [ Time Frame: 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.
6. 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 [ Time Frame: 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.
7. DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs [ Time Frame: 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.
8. OL Period: Number of Participants With AEs and Who Did Not Complete the Study Due to AEs [ Time Frame: 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.
9. DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results [ Time Frame: 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.
10. OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results [ Time Frame: 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.
11. DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results [ Time Frame: 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.
12. OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results [ Time Frame: 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.
13. DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results [ Time Frame: 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.
14. OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results [ Time Frame: 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.
15. DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results [ Time Frame: 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.
16. OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results [ Time Frame: 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.
17. DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values [ Time Frame: 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.
18. OL Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values [ Time Frame: 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.
19. DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters [ Time Frame: 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.
20. OL Period: Number of Participants With Shift From Baseline to Week 24 in ECG Parameters [ Time Frame: 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.
21. DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events [ Time Frame: 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.
22. OL Period: Number of Participants Who Received Concomitant Medications for Adverse Events [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Teva Investigational Site 14742

Huntsville, Alabama, United States, 35801

United States, California

Teva Investigational Site 14729

Long Beach, California, United States, 90806

Teva Investigational Site 14739

San Diego, California, United States, 92103

Teva Investigational Site 14843

Santa Monica, California, United States, 90404

United States, Colorado

Teva Investigational Site 14749

Colorado Springs, Colorado, United States, 80918

United States, Florida

Teva Investigational Site 14758

Maitland, Florida, United States, 32751

Teva Investigational Site 14738

Orlando, Florida, United States, 32819

United States, Georgia

Teva Investigational Site 14760

Decatur, Georgia, United States, 30030

United States, Idaho

Teva Investigational Site 14737

Meridian, Idaho, United States, 83642

United States, Illinois

Teva Investigational Site 14730

Chicago, Illinois, United States, 60607

Teva Investigational Site 14740

Evanston, Illinois, United States, 60201

United States, Kentucky

Teva Investigational Site 14735

Louisville, Kentucky, United States, 40223

United States, Maryland

Teva Investigational Site 14747

Pikesville, Maryland, United States, 21208

United States, Massachusetts

Teva Investigational Site 14750

Fall River, Massachusetts, United States, 02720

Teva Investigational Site 14734

Watertown, Massachusetts, United States, 02472

United States, Michigan

Teva Investigational Site 14731

Ann Arbor, Michigan, United States, 48104

United States, Minnesota

Teva Investigational Site 14748

Plymouth, Minnesota, United States, 55441

United States, Nebraska

Teva Investigational Site 14746

Omaha, Nebraska, United States, 68114

United States, New Jersey

Teva Investigational Site 14754

Berlin, New Jersey, United States, 08009

United States, New Mexico

Teva Investigational Site 14752

Albuquerque, New Mexico, United States, 87102

United States, New York

Teva Investigational Site 14753

Amherst, New York, United States, 14226

United States, North Carolina

Teva Investigational Site 14736

Greensboro, North Carolina, United States, 27405

Teva Investigational Site 14741

Greensboro, North Carolina, United States, 27408

Teva Investigational Site 14732

Raleigh, North Carolina, United States, 27607

United States, Rhode Island

Teva Investigational Site 14761

Lincoln, Rhode Island, United States, 02865

Teva Investigational Site 14756

Warwick, Rhode Island, United States, 02886

United States, Tennessee

Teva Investigational Site 14745

Memphis, Tennessee, United States, 38119

Teva Investigational Site 14743

Nashville, Tennessee, United States, 37203

United States, Texas

Teva Investigational Site 14733

Austin, Texas, United States, 78731

United States, Utah

Teva Investigational Site 14751

West Jordan, Utah, United States, 84088

Belgium

Teva Investigational Site 37092

Brugge, Belgium, 8000

Teva Investigational Site 37089

Brussels, Belgium, 1090

Teva Investigational Site 37091

Hasselt, Belgium, 3500

Teva Investigational Site 37090

Liege, Belgium, 4000

Czechia

Teva Investigational Site 54162

Brno, Czechia, 602 00

Teva Investigational Site 54165

Ostrava-Moravska, Czechia, 702 00

Teva Investigational Site 54159

Ostrava, Czechia, 70200

Teva Investigational Site 54158

Pardubice, Czechia, 53002

Teva Investigational Site 54164

Prague 4, Czechia, 140 59

Teva Investigational Site 54163

Prague, Czechia, 100 00

Teva Investigational Site 54160

Praha 10, Czechia, 160 00

Teva Investigational Site 54161

Praha 3, Czechia, 130 00

Teva Investigational Site 54166

Praha 8, Czechia, 186 00

Teva Investigational Site 54157

Rychnov nad Kneznou, Czechia, 51601

Denmark

Teva Investigational Site 39051

Aalborg, Denmark, 9000

Teva Investigational Site 39049

Arhus, Denmark, 8000

Teva Investigational Site 39052

Ballerup, Denmark, 2750

Teva Investigational Site 39048

Glostrup, Denmark, 2600

Teva Investigational Site 39050

Vejle, Denmark, 7100

Finland

Teva Investigational Site 40034

Helsinki, Finland, 00180

Teva Investigational Site 40035

Helsinki, Finland, 00930

Teva Investigational Site 40036

Oulu, Finland, 90100

Teva Investigational Site 40033

Tampere, Finland, FI-33100

Teva Investigational Site 40032

Turku, Finland, 20100

Teva Investigational Site 40037

Turku, Finland, 20520

France

Teva Investigational Site 35237

Bron Cedex, France, 69677

Teva Investigational Site 35238

Lille, France, 59037

Teva Investigational Site 35235

Marseille, France, 13005

Teva Investigational Site 35240

Nice, France, 06000

Teva Investigational Site 35239

Strasbourg, France, 67098

Teva Investigational Site 35236

Voiron, France, 38500

Germany

Teva Investigational Site 32697

Berlin, Germany, 10177

Teva Investigational Site 32690

Berlin, Germany, D-10435

Teva Investigational Site 32694

Bochum, Germany, 44787

Teva Investigational Site 32699

Essen, Germany, 45147

Teva Investigational Site 32692

Goppingen, Germany, 73033

Teva Investigational Site 32691

Halle, Germany, 06120

Teva Investigational Site 32698

Hamburg, Germany, 20251

Teva Investigational Site 32700

Kiel, Germany, 24149

Teva Investigational Site 32695

Konigstein im Taunus, Germany, 61462

Teva Investigational Site 32689

Muenchen, Germany, 81377

Teva Investigational Site 32701

Rostock, Germany, 18147

Teva Investigational Site 32693

Ulm, Germany, 89073

Italy

Teva Investigational Site 30199

Firenze, Italy, 50134

Teva Investigational Site 30204

Roma, Italy, 00128

Netherlands

Teva Investigational Site 38126

Amsterdam, Netherlands, 1078VV

Teva Investigational Site 38127

Blaricum, Netherlands, 1261 AN

Teva Investigational Site 38124

Leiden, Netherlands, 2333 ZA

Teva Investigational Site 38125

Tilburg, Netherlands, 5042 AD

Poland

Teva Investigational Site 53420

Krakow, Poland, 31-209

Teva Investigational Site 53425

Krakow, Poland, 33-332

Teva Investigational Site 53422

Lodz, Poland, 90-338

Teva Investigational Site 53424

Lodz, Poland, 90-368

Teva Investigational Site 53418

Lublin, Poland, 20-022

Teva Investigational Site 53416

Poznan, Poland, 60-529

Teva Investigational Site 53419

Szczecin, Poland, 70-111

Teva Investigational Site 53417

Warszawa, Poland, 00-909

Teva Investigational Site 53423

Warszawa, Poland, 04-730

Spain

Teva Investigational Site 31231

Barcelona, Spain, 08035

Teva Investigational Site 31235

Madrid, Spain, 28223

Teva Investigational Site 31236

Madrid, Spain, 28942

Teva Investigational Site 31226

Pamplona, Spain, 31008

Teva Investigational Site 31229

Santander, Spain, 39008

Teva Investigational Site 31230

Santiago de Compostela, Spain, 15706

Teva Investigational Site 31234

Sevilla, Spain, 41013

Teva Investigational Site 31233

Valencia, Spain, 46010

Teva Investigational Site 31227

Valencia, Spain, 46026

Teva Investigational Site 31225

Valladolid, Spain, 47003

Teva Investigational Site 31228

Zaragoza, Spain, 50009

Sweden

Teva Investigational Site 42050

Helsingborg, Sweden, 252 20

Teva Investigational Site 42049

Huddinge, Sweden, 141 86

Teva Investigational Site 42051

Lund, Sweden, 260 83

Teva Investigational Site 42052

Stockholm, Sweden, 112 81

Teva Investigational Site 42054

Stockholm, Sweden, 114 33

Switzerland

Teva Investigational Site 45018

Bad Zurzach, Switzerland, 5330

Teva Investigational Site 45016

Bern, Switzerland, 3010

Teva Investigational Site 45017

Lugano, Switzerland, 6900

United Kingdom

Teva Investigational Site 34231

Glasgow, United Kingdom, G51 4TF

Teva Investigational Site 34232

Hull, United Kingdom, HU3 2JZ

Teva Investigational Site 34233

London, United Kingdom, SE5 9NT

Teva Investigational Site 34230

Oxford, United Kingdom, OX3 9DU

Teva Investigational Site 34235

Salford, United Kingdom, M6 8HD

Teva Investigational Site 34236

Stoke-on-Trent, United Kingdom, ST4 6QG

Sponsors and Collaborators

Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, MD; Teva Branded Pharmaceutical Products R&D, Inc.

  Study Documents (Full-Text)

Documents provided by Teva Branded Pharmaceutical Products R&D, Inc.:

Study Protocol  [PDF] October 23, 2017

Statistical Analysis Plan  [PDF] November 13, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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;:

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT03308968
• Other Study ID Numbers: TV48125-CNS-30068; 2017-002441-30 ( EudraCT Number )
• First Posted: October 13, 2017
• Results First Posted: October 9, 2019
• Last Update Posted: November 9, 2021
• Last Verified: November 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases