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

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy, Safety, and Tolerability of Subcutaneous Administration of Fremanezumab Versus Placebo for the Preventive Treatment of Chronic Migraine in Pediatric Patients 6 to 17 Years of Age

The primary objective of the study is to evaluate the effectiveness of fremanezumab as compared to placebo for the preventive treatment of chronic migraine (CM).

Secondary objectives are to further demonstrate the efficacy of Fremanezumab as compared to placebo for the preventive treatment of CM, to evaluate the safety and tolerability of Fremanezumab in the preventive treatment of CM and to evaluate the immunogenicity of Fremanezumab and the impact of antidrug antibodies (ADAs) on clinical outcomes in participants exposed to Fremanezumab

The total duration of the study is planned to be 75 months.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 278
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Teva U.S. Medical Information; Phone Number: 1-888-483-8279; Email: USMedInfo@tevapharm.com

Study Locations

• Canada
  • Ontario
    • Ajax, Ontario, Canada, L1Z 0M1
      • Completed
      • Teva Investigational Site 11180
    • Nepean, Ontario, Canada, K2G 1W2
      • Terminated
      • Teva Investigational Site 11179
    • Ottawa, Ontario, Canada, K1H 8L1
      • Recruiting
      • Teva Investigational Site 11182
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Teva Investigational Site 11181
• Finland
  • Helsinki, Finland, 00380
    • Recruiting
    • Teva Investigational Site 40053
  • Kuopio, Finland, 70210
    • Recruiting
    • Teva Investigational Site 40049
  • Oulu, Finland, 90100
    • Recruiting
    • Teva Investigational Site 40054
  • Tampere, Finland, 33521
    • Recruiting
    • Teva Investigational Site 40052
• Germany
  • Bad Homburg, Germany, 61350
    • Recruiting
    • Teva Investigational Site 32728
  • Berlin, Germany, 13353
    • Recruiting
    • Teva Investigational Site 32729
  • Dresden, Germany, 01307
    • Terminated
    • Teva Investigational Site 32725
  • Essen, Germany, 452133
    • Completed
    • Teva Investigational Site 32724
  • Leipzig, Germany, 04103
    • Recruiting
    • Teva Investigational Site 32726
• Israel
  • Be'er Ya'akov, Israel, 7033001
    • Recruiting
    • Teva Investigational Site 80170
  • Haifa, Israel, 3339419
    • Recruiting
    • Teva Investigational Site 80166
  • Holon, Israel, 58100
    • Recruiting
    • Teva Investigational Site 80168
  • Jerusalem, Israel, 9124001
    • Recruiting
    • Teva Investigational Site 80169
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Teva Investigational Site 80167
  • Safed, Israel, 1311001
    • Recruiting
    • Teva Investigational Site 80164
  • Tel-Aviv, Israel, 6423906
    • Recruiting
    • Teva Investigational Site 80165
• Italy
  • Firenze, Italy, 50139
    • Recruiting
    • Teva Investigational Site 30230
  • Milano, Italy, 20132
    • Recruiting
    • Teva Investigational Site 30239
  • Milano, Italy, 20154
    • Recruiting
    • Teva Investigational Site 30226
  • Milano, Italy, 20133
    • Recruiting
    • Teva Investigational Site 30228
  • Padua, Italy, 35128
    • Recruiting
    • Teva Investigational Site 30238
  • Pavia, Italy, 27100
    • Recruiting
    • Teva Investigational Site 30227
  • Rome, Italy, 00163
    • Recruiting
    • Teva Investigational Site 30225
• Netherlands
  • Doetinchem, Netherlands, 7009 BL
    • Recruiting
    • Teva Investigational Site 38138
  • Nijmegen, Netherlands, 6532 SZ
    • Recruiting
    • Teva Investigational Site 38135
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Teva Investigational Site 38136
• Poland
  • Gdansk, Poland, 80-389
    • Recruiting
    • Teva Investigational Site 53441
  • Kielce, Poland, 25-316
    • Recruiting
    • Teva Investigational Site 53437
  • Krakow, Poland, 30-363
    • Recruiting
    • Teva Investigational Site 53443
  • Krakow, Poland, 30-539
    • Recruiting
    • Teva Investigational Site 53452
  • Lublin, Poland, 20-582
    • Recruiting
    • Teva Investigational Site 53440
  • Poznan, Poland, 60-355
    • Recruiting
    • Teva Investigational Site 53439
  • Poznan, Poland, 61-731
    • Recruiting
    • Teva Investigational Site 53451
  • Szczecin, Poland, 70-111
    • Recruiting
    • Teva Investigational Site 53442
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Teva Investigational Site 31271
  • Elda, Spain, 03600
    • Terminated
    • Teva Investigational Site 31266
  • Madrid, Spain, 28046
    • Completed
    • Teva Investigational Site 31267
  • Madrid, Spain, 28007
    • Completed
    • Teva Investigational Site 31268
  • Valencia, Spain, 46026
    • Completed
    • Teva Investigational Site 31270
  • Valladolid, Spain, 47010
    • Recruiting
    • Teva Investigational Site 31265
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Completed
      • Teva Investigational Site 14281
  • California
    • Banning, California, United States, 92220
      • Completed
      • Teva Investigational Site 14253
    • Loma Linda, California, United States, 92354
      • Terminated
      • Teva Investigational Site 14370
    • Los Angeles, California, United States, 90027
      • Terminated
      • Teva Investigational Site 14322
    • Sacramento, California, United States, 95815
      • Terminated
      • Teva Investigational Site 14361
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Teva Investigational Site 14319
    • Colorado Springs, Colorado, United States, 80907
      • Recruiting
      • Teva Investigational Site 14368
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Teva Investigational Site 14244
    • Miami, Florida, United States, 33155
      • Recruiting
      • Teva Investigational Site 14325
    • Miami, Florida, United States, 33186
      • Completed
      • Teva Investigational Site 14316
    • West Palm Beach, Florida, United States, 33407
      • Recruiting
      • Teva Investigational Site 14250
    • West Palm Beach, Florida, United States, 33409
      • Completed
      • Teva Investigational Site 14255
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Terminated
      • Teva Investigational Site 14243
    • Savannah, Georgia, United States, 31406
      • Recruiting
      • Teva Investigational Site 14258
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Recruiting
      • Teva Investigational Site 14263
    • Park Ridge, Illinois, United States, 60068
      • Completed
      • Teva Investigational Site 14283
  • Kansas
    • Wichita, Kansas, United States, 67206
      • Recruiting
      • Teva Investigational Site 14245
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Teva Investigational Site 14327
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Recruiting
      • Teva Investigational Site 14360
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Teva Investigational Site 14365
    • Silver Spring, Maryland, United States, 20910
      • Terminated
      • Teva Investigational Site 14317
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Recruiting
      • Teva Investigational Site 14246
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Recruiting
      • Teva Investigational Site 14251
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Completed
      • Teva Investigational Site 14270
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • Recruiting
      • Teva Investigational Site 14376
  • Missouri
    • Bridgeton, Missouri, United States, 63044-2513
      • Terminated
      • Teva Investigational Site 14256
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Teva Investigational Site 14371
  • New York
    • Amherst, New York, United States, 14226
      • Recruiting
      • Teva Investigational Site 14276
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Teva Investigational Site 14377
    • Raleigh, North Carolina, United States, 27607
      • Completed
      • Teva Investigational Site 14248
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Recruiting
      • Teva Investigational Site 14264
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Recruiting
      • Teva Investigational Site 14257
    • Oklahoma City, Oklahoma, United States, 73116
      • Completed
      • Teva Investigational Site 14275
    • Tulsa, Oklahoma, United States, 74136
      • Completed
      • Teva Investigational Site 14363
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4318
      • Recruiting
      • Teva Investigational Site 14364
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Recruiting
      • Teva Investigational Site 14374
  • Texas
    • Austin, Texas, United States, 78759
      • Completed
      • Teva Investigational Site 14273
    • Austin, Texas, United States, 78731
      • Recruiting
      • Teva Investigational Site 14252
    • Dallas, Texas, United States, 75235
      • Recruiting
      • Teva Investigational Site 14367
    • Houston, Texas, United States, 77087
      • Completed
      • Teva Investigational Site 14312
    • Houston, Texas, United States, 77024
      • Completed
      • Teva Investigational Site 14274
    • San Antonio, Texas, United States, 78240
      • Completed
      • Teva Investigational Site 14241
    • San Antonio, Texas, United States, 78207
      • Terminated
      • Teva Investigational Site 14366
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Recruiting
      • Teva Investigational Site 14375
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Recruiting
      • Teva Investigational Site 14323
  • Washington
    • Tacoma, Washington, United States, 98405
      • Completed
      • Teva Investigational Site 14277

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant has a clinical history of recurrent headache consistent with the diagnosis of migraine for at least 6 months before screening, consistent with ICHD-3 criteria (Headache Classification Committee of the IHS 2013), and a history of ≥15 headache days per month on average during the 3 months prior to screening (visit 1).
• The participant or parent/caregiver maintain a prospectively collected headache diary

NOTE: Additional criteria apply; please contact the investigator for more information.

Exclusion Criteria:

• The participant is using medications containing opioids (including codeine) or barbiturates (including Fiorinal®, Fioricet®, or any other combination containing butalbital) for the treatment of migraine during the 3 months prior to the day of the screening visit.
• The participant has used an intervention/device (eg, scheduled nerve block or transcranial magnetic stimulation) for the treatment of migraine or in the head or neck area for any condition during the 2 months prior to the day of the screening visit.
• The participant has a current history of a clinically significant psychiatric condition, at the discretion of the investigator. Any prior history of a suicide attempt, or a history of suicidal ideation with a specific plan within the past 2 years must be excluded.
• The participant has an ongoing infection or a known history of human immunodeficiency virus infection, tuberculosis, Lyme disease, or chronic hepatitis B or C, or a known active infection of coronavirus disease 2019 (COVID-19).
• The participant has a past or current history of cancer.
• The participant is pregnant or nursing.
• The participant has a history of hypersensitivity reactions to injected proteins, including mAbs, or a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome, or the participant is concomitantly using lamotrigine.
• The participant received a live attenuated vaccine (eg, intranasal flu vaccine, and measles, mumps, and rubella vaccine) within the 12-week period prior to screening. Note: If a medical need arises during the study, the participant may receive a live attenuated vaccine.
• The patient has a current or past medical history of hemiplegic migraine.

NOTE: 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Matching placebo
Experimental: Fremanezumab; Participants weighing ≥ threshold will receive Dose A subcutaneously monthly for 3 months. Participants weighing < threshold will receive Dose B subcutaneously monthly for 3 months.	Drug: Fremanezumab; Dose A or Dose B subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change in the monthly average number of migraine days after the first dose of study drug	Baseline - Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in the monthly average number of days of use of any acute headache medications after the first dose of study drug		Baseline - Month 3
Mean change in the PedMIDAS questionnaire after administration of the first dose of study drug	The Pediatric Migraine Disability Assessment (PedMIDAS) is used to assess migraine disability across multiple domains of functioning including school, home, social, and recreational. The measure consists of 6 items measuring the number of days in which activities were missed as a result of headache/migraine. The measure yields a total score by summing items. Total scores correspond to one of four "disability grades:" 0-10 = little to no disability, 11-30 = mild disability, 31-50 = moderate disability, and >50 = severe disability.	Baseline and Month 3
Mean change PedsQL after administration of the first dose of study drug	Pediatric Quality of Life Inventory (PedsQL) A health-related quality-of-life instrument that consists of a well-validated generic core measure and some condition and disease-specific modules. The instructions ask how much of a problem each item has been during the past 1 month. A 5-point response scale is utilized across child self-report and parent proxy report as follows: 0=never a problem; almost never a problem;; sometimes a problem;; often a problem;; almost always a problem.	Baseline - Month 3
Number of adverse events	including local injection site reaction/pain	Baseline - Month 3
Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings		Baseline - Month 3
Incidence of abnormal vital signs	(systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements	Baseline - Month 3
Number of participants with clinically significant changes in laboratory values		Baseline, Month 1, and Month 3
Incidence of abnormal physical examination findings		Baseline - Month 3
Yes/No suicidality ideation	Columbia-Suicide Severity Rating Scale (C-SSRS) The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Scale range: Yes or No response to 10 questions, with minimum to maximum range of 0 to 10. Lower score represents better outcomes.	Screening - Month 3
Mean change in monthly average number of headache days of at least moderate severity after the first dose of study drug		Baseline - Month 3
Proportion of participants reaching at least 50% reduction in the monthly average number of migraine days after the first dose of study drug		Baseline - Month 3
Proportion of participants developing antidrug antibodies (ADAs) throughout the study	The impact of ADAs on safety and efficacy will be analyzed if the number of ADA-positive participants allows.	Baseline - Month 3

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Estimated): February 22, 2025
• Study Completion (Estimated): February 22, 2025

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

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-30082; 2019-002053-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please visit www.clinicalstudydatarequest.com to make your request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No